epiglucan and Neoplasms

Cancer is characterized by a perturbed immune landscape. Inside tumor microenvironment, immune system is reprogrammed to facilitate tumor growth and survival rather than eliminating it. This immune evasive mechanism needs to be reversed to normal for effective anticancer therapeutic strategy. Immunotherapy has emerged as a novel strategy for redeployment of immune cells against cancer. However, they suffer in their efficacy, response rate and side effects. This necessitated us to turn toward natural repertoires which can act as a substitute to conventional immunotherapeutics. Beta glucan, a polysaccharide derived from mushroom, serves the role of immunomodulator inside tumor microenvironment. It acts as pathogen associated molecular pattern and bind to various pattern recognition receptors expressed on surface of immune cells thereby facilitating their activation and crosstalk. This result in resurgence of suppressed immune surveillance in the tumor milieu. In this review, we highlight in brief the advances and limitation of cancer immunotherapy. Alongside, we have discussed the detailed mechanistic principle and recent advances underlying restoration of immune functionality by beta glucan.

Topics: beta-Glucans; Humans; Immunotherapy; Macrophages; Neoplasms; Tumor Microenvironment

β-glucans are a large class of complex polysaccharides found in abundant sources. Our dietary sources of β-glucans are cereals that include oats and barley, and non-cereal sources can consist of mushrooms, microalgae, bacteria, and seaweeds. There is substantial clinical interest in β-glucans; as they can be used for a variety of diseases including cancer and cardiovascular conditions. Suitable sources of β-glucans for biopharmaceutical applications include bacteria, microalgae, mycelium, and yeast. Environmental factors including culture medium can influence the biomass and ultimately β-glucan content. Therefore, cultivation conditions for the above organisms can be controlled for sustainable enhanced production of β-glucans. This review discusses the various sources of β-glucans and their cultivation conditions that may be optimised to exploit sustainable production. Finally, this article discusses the immune-modulatory potential of β-glucans from these sources.

Topics: Agaricales; beta-Glucans; Humans; Immunity; Neoplasms; Pharmaceutical Preparations; Saccharomyces cerevisiae

Since ancient times, mushrooms have been considered valuable allies of human well-being both from a dietary and medicinal point of view. Their essential role in several traditional medicines is explained today by the discovery of the plethora of biomolecules that have shown proven efficacy for treating various diseases, including cancer. Numerous studies have already been conducted to explore the antitumoural properties of mushroom extracts against cancer. Still, very few have reported the anticancer properties of mushroom polysaccharides and mycochemicals against the specific population of cancer stem cells (CSCs). In this context, β-glucans are relevant in modulating immunological surveillance against this subpopulation of cancer cells within tumours. Small molecules, less studied despite their spread and assortment, could exhibit the same importance. In this review, we discuss several pieces of evidence of the association between β-glucans and small mycochemicals in modulating biological mechanisms which are proven to be involved with CSCs development. Experimental evidence and an in silico approach are evaluated with the hope of contributing to future strategies aimed at the direct study of the action of these mycochemicals on this subpopulation of cancer cells.

Topics: Agaricales; beta-Glucans; Humans; Neoplasms; Neoplastic Stem Cells; Polysaccharides

The incidence of cancer, which is the second leading cause of mortality globally, continues to increase, although continued efforts are being made to identify effective treatments with fewer side‑effects. Previous studies have reported that chronic microinflammation, which occurs in diseases, including diabetes, along with weakened immune systems, may ultimately lead to cancer development. Chemotherapy, radiotherapy and surgery are the mainstream approaches to treatment; however, they all lead to immune system weakness, which in turn increases the metastatic spread. The aim of the present review was to provide evidence of a biological response modifier β‑glucan [β‑glucan vaccine adjuvant approach to treating cancer via immune enhancement (B‑VACCIEN)] and its beneficial effects, including vaccine‑adjuvant potential, balancing metabolic parameters (including blood glucose and lipid levels), increasing peripheral blood cell cytotoxicity against cancer and alleviating chemotherapy side effects in animal models. This suggests its value as a potential strategy to provide long‑term prophylaxis in immunocompromised individuals or genetically prone to cancer.

Topics: Adjuvants, Vaccine; Animals; beta-Glucans; Humans; Immunocompromised Host; Neoplasms

β-glucans are a diverse group of polysaccharides composed of β-1,3 or β-(1,3-1,4) linked glucose monomers. They are mainly synthesized by fungi, plants, seaweed and bacteria, where they carry out structural, protective and energy storage roles. Because of their unique physicochemical properties, they have important applications in several industrial, biomedical and biotechnological processes. β-glucans are also major bioactive molecules with marked immunomodulatory and metabolic properties. As such, they have been the focus of many studies attesting to their ability to, among other roles, fight cancer, reduce the risk of cardiovascular diseases and control diabetes. The physicochemical and functional profiles of β-glucans are deeply influenced by their molecular structure. This structure governs β-glucan interaction with multiple β-glucan binding proteins, triggering myriad biological responses. It is then imperative to understand the structural properties of β-glucans to fully reveal their biological roles and potential applications. The deconstruction of β-glucans is a result of β-glucanase activity. In addition to being invaluable tools for the study of β-glucans, these enzymes have applications in numerous biotechnological and industrial processes, both alone and in conjunction with their natural substrates. Here, we review potential applications for β-glucans and β-glucanases, and explore how their functionalities are dictated by their structure.

Topics: beta-Glucans; Fungi; Molecular Structure; Neoplasms; Plants; Polysaccharides

This article is dedicated to the 75th anniversary of Solomon P. Wasser and discusses the challenges within the research direction he founded with Professors T. Mizuno, S.T. Chang, and other colleagues, known as medicinal mushroom science. This research organically grows out of taxonomic studies, since understanding of the classification system leads to greater ability to make forecasts and predictions in the practical field as well as to increase knowledge of close relationships between organisms, allowing greater eeconomic organization within the search and screening for new practically significant organisms. Through the efforts of Professors Wasser, Mizuno, and Chang, the International Journal of Medicinal Mushrooms (IJMM) was created, combining the efforts of physicians using mushroom raw materials as an auxiliary tool and specialists in fungal biotechnology. In this work, the basic prerequisites for cancer mycotherapy are described, based on data on the mechanism of action of fungal metabolites on cancer targets. A large section of this report is devoted to a review of evidence-based medicine tools and an overview of their use among teams of Chinese researchers. It has been shown that the main recipients of mycotherapy, as well as other types of immunotherapies, are patients with stage 3 cancer who have undergone surgery to remove the primary tumor node and are undergoing chemotherapy; for these patients, their immune status must be increased, and the immune system requires a periodic rebooting. In this respect, Dectin stimulation using fungal glucans is comparable to cytokine therapy and can be characterized as an "endogenous cytokine therapy." The results of the combined treatment at this stage are to be quantified using evidence-based medicine tools, for which we recommend including the consumption of mushroom extracts in the patient questionnaire. This article also discusses challenges in the pharmacokinetics of β-glucans and triterpenoids.

Topics: Agaricales; beta-Glucans; Cytokines; Humans; Immunotherapy; Neoplasms

Use of polysaccharides as carriers in drug delivery system is a hot topic, especially those with specific recognition of immune cells, enabling them to be applied in targeting delivery system. β-d-glucans are naturally occurring non-digestible polysaccharides with immunomodulatory activities that have attracted increasing attention to serve as therapeutic agents or immune-adjuvants. Being able to be specifically recognized by immune cells like macrophages, β-d-glucans can be developed as promising carriers for targeting delivery with stability, biocompatibility and specificity when applied in immunotherapy. Targeting tumor associated macrophages (TAMs) is an emerging strategy for cancer immunotherapy since it exerts anti-cancer effects based on modulating body immunity in tumor microenvironment (TME). This new strategy does not require high concentration of drugs to kill cancer cells directly and lessen tumor recurrence by creating unique immune memory for malignant cells. In this review, construction strategies of polysaccharide-based drug delivery system of three types of β-d-glucan including non-yeast and yeast β-d-glucans as well as hyper-branched β-d-glucan are discussed with reference to their branching characteristics and conformation. The applications of these β-d-glucans as nano-carrier for drug delivery targeting TAMs are also discussed.

Topics: Animals; beta-Glucans; Drug Carriers; Humans; Immunologic Factors; Immunotherapy; Molecular Conformation; Neoplasms; Solubility; Tumor Microenvironment; Tumor-Associated Macrophages; Yeasts

Fungal β-glucans have been considered as biological response modifiers (BRMs) promoting stimulation of immune system according to numerous scientific publications performed in vitro and in vivo. Some clinical trials involving such compounds started to be published since 1980's. This systematic review aimed to compile and compare clinical studies using these β-glucans as adjuvants on patients undergoing cancer treatment. Healthy subjects and β-glucans from other sources were excluded.. It was developed according to PRISMA-P guidelines (PROSPERO registered n. CRD42020151539), using PICO criteria and the following databases: PubMed, Scielo and LILACS.. We found 1018 articles and after removing duplicated records, select by title/abstract and full-text, only 9 studies remained and 7 more were manually added, totalizing 16 trials involving 1650 patients, with arm sizes varying from 9 until 200 patients. The selected studies (published since 1992-2018) included subjects with diagnosis of 9 types of cancer. The studies used different sources of β-glucans, such as yeast (Saccharomyces cerevisiae), mushrooms (Lentinula edodes and Schizophyllum commune) and non-described fungal sources.. It was observed that the administration of β-glucan is safe and well-tolerated. Most of the trials pointed that concomitant administration of β-glucan with chemo or radiotherapy reduced the immune depression caused by such treatments and/or accelerated the recovery of white blood cells counts. However, some articles also commented that no statistical difference was encountered between β-glucan treated vs. control groups, which gives a controversial conclusion about the β-glucan effects. The great diversity among the methodology studies and insufficient information was an impeditive for achieving profound statistical analysis, therefore a narrative report of the included studies was performed indicating that further evidences are required to determine the efficacy of this adjuvant in the cancer treatment.

Topics: beta-Glucans; Combined Modality Therapy; Fungi; Humans; Immunologic Factors; Neoplasms

β-glucans are linear polysaccharides of d-glucose monomers linked through β-glycosidic bonds and are widely present in nature. Different sources lead to their structural differences. β-glucan has long been acknowledged to be a safe and functional component. Its biological activities include lipid-lowering, hypoglycemic, antitumor and immune regulation etc. A large number of studies have shown that soluble β-glucan can bind to their receptors on the surface of immune cells, activates the pro-inflammatory response of innate immune cells, and enhances the host's antitumor defense. A variety of soluble β-glucans have been widely used in clinical antitumor studies as an immunostimulant to treat the cancer patient. In this paper, we reviewed the molecular structure, antitumor immune activities, structure-activity relationship and clinical trials of soluble β-glucans in order to provide the overall scene of β-glucans as immunostimulant to fight the cancer.

Topics: Adjuvants, Immunologic; Animals; beta-Glucans; Humans; Neoplasms

Postbiotics are health-promoting microbial metabolites delivered as a functional food or a food supplement. They either directly influence signaling pathways of the body or indirectly manipulate metabolism and the composition of intestinal microflora. Cancer is the second leading cause of death worldwide and even though the prognosis of patients is improving, it is still poor in the substantial part of the cases. The preventable nature of cancer and the importance of a complex multi-level approach in anticancer therapy motivate the search for novel avenues of establishing the anticancer environment in the human body. This review summarizes the principal findings demonstrating the usefulness of both natural and synthetic sources of postbotics in the prevention and therapy of cancer. Specifically, the effects of crude cell-free supernatants, the short-chain fatty acid butyrate, lactic acid, hydrogen sulfide, and β-glucans are described. Contradictory roles of postbiotics in healthy and tumor tissues are highlighted. In conclusion, the application of postbiotics is an efficient complementary strategy to combat cancer.

Topics: beta-Glucans; Butyrates; Dietary Supplements; Fatty Acids, Volatile; Gastrointestinal Microbiome; Humans; Hydrogen Sulfide; Lactic Acid; Metabolome; Neoplasms; Prebiotics; Probiotics

Cancer is considered a fetal disease caused by uncontrolled proliferation and progression of abnormal cells. The most efficient cancer therapies suppress tumor growth, prevent progression and metastasis, and are minimally toxic to normal cells. Natural compounds have shown a variety of chemo-protective effects alone or in combination with standard cancer therapies. Along with better understanding of the dynamic interactions between our immune system and cancer development, nutritional immunology-the use of natural compounds as immunomodulators in cancer patients-has begun to emerge. Cancer cells evolve strategies that target many aspects of the immune system to escape or even edit immune surveillance. Therefore, the immunesuppressive tumor microenvironment is a major obstacle in the development of cancer therapies. Because interaction between the tumor microenvironment and the immune system is a complex topic, this review focuses mainly on human clinical trials and animal studies, and it highlights specific immune cells and their cytokines that have been modulated by natural compounds, including carotenoids, curcumin, resveratrol, EGCG, and β-glucans. These natural compounds have shown promising immune-modulating effects, such as inhibiting myeloid-derived suppressor cells and enhancing natural killer and cytolytic T cells, in tumor-bearing animal models, but their efficacy in cancer patients remains to be determined.

Topics: Animals; beta-Glucans; Carotenoids; Catechin; Curcumin; Humans; Immune System; Immunologic Factors; Killer Cells, Natural; Mice; Neoplasms; Resveratrol; T-Lymphocytes; Tretinoin; Tumor Microenvironment

An increased understanding of the complex mechanisms at play within the tumor microenvironment (TME) has emphasized the need for the development of strategies that target immune cells within the TME. Therapeutics that render the TME immune-reactive have a vast potential for establishing effective cancer interventions. One such intervention is β-glucan, a natural compound with immune-stimulatory and immunomodulatory potential that has long been considered an important anti-cancer therapeutic. β-glucan has the ability to modulate the TME both by bridging the innate and adaptive arms of the immune system and by modulating the phenotype of immune-suppressive cells to be immune-stimulatory. New roles for β-glucan in cancer therapy are also emerging through an evolving understanding that β-glucan is involved in a concept called trained immunity, where innate cells take on memory phenotypes. Additionally, the hollow structure of particulate β-glucan has recently been harnessed to utilize particulate β-glucan as a delivery vesicle. These new concepts, along with the emerging success of combinatorial approaches to cancer treatment involving β-glucan, suggest that β-glucan may play an essential role in future strategies to prevent and inhibit tumor growth. This review emphasizes the various characteristics of β-glucan, with an emphasis on fungal β-glucan, and highlights novel approaches of β-glucan in cancer therapy.

Topics: beta-Glucans; Dendritic Cells; Humans; Neoplasms; Saccharomyces cerevisiae; Tumor Microenvironment

Immunotherapy is revolutionizing cancer treatment. Recent clinical success with immune checkpoint inhibitors, chimeric antigen receptor T-cell therapy, and adoptive immune cellular therapies has generated excitement and new hopes for patients and investigators. However, clinically efficacious responses to cancer immunotherapy occur only in a minority of patients. One reason is the tumor microenvironment (TME), which potently inhibits the generation and delivery of optimal antitumor immune responses. As our understanding of TME continues to grow, strategies are being developed to change the TME toward one that augments the emergence of strong antitumor immunity. These strategies include eliminating tumor bulk to provoke the release of tumor antigens, using adjuvants to enhance antigen-presenting cell function, and employ agents that enhance immune cell effector activity. This article reviews the development of β-glucan and β-glucan-based nanoparticles as immune modulators of TME, as well as their potential benefit and future therapeutic applications. Cell-wall β-glucans from natural sources including plant, fungi, and bacteria are molecules that adopt pathogen-associated molecular pattern (PAMP) known to target specific receptors on immune cell subsets. Emerging data suggest that the TME can be actively manipulated by β-glucans and their related nanoparticles. In this review, we discuss the mechanisms of conditioning TME using β-glucan and β-glucan-based nanoparticles, and how this strategy enables future design of optimal combination cancer immunotherapies.

Topics: Animals; Antigens, Neoplasm; beta-Glucans; Humans; Immunologic Factors; Immunotherapy; Nanoparticles; Neoplasms; Tumor Microenvironment

Adoptive T-cell treatments of solid cancers have evolved into a robust therapy with objective response rates surpassing those of standardized treatments. Unfortunately, only a limited fraction of patients shows durable responses, which is considered to be due to a T cell-suppressive tumor microenvironment (TME). Here we argue that naturally occurring β-glucans can enable reversion of such T cell suppression by engaging innate immune cells and enhancing numbers and function of lymphocyte effectors.. This review summarizes timely reports with respect to absorption, trafficking and immune stimulatory effects of β-glucans, particularly in relation to innate immune cells. Furthermore, we list effects toward well-being and immune functions in healthy subjects as well as cancer patients treated with orally administered β-glucans, extended with effects of β-glucan treatments in mouse cancer models.. Beta-glucans, when present in food and following uptake in the proximal gut, stimulate immune cells present in gut-associated lymphoid tissue and initiate highly conserved pro-inflammatory pathways. When tested in mouse cancer models, β-glucans result in better control of tumor growth and shift the TME toward a T cell-sensitive environment. Along these lines, we advocate that intake of β-glucans provides an accessible and immune-potentiating adjuvant when combined with adoptive T-cell treatments of cancer.

Topics: Adjuvants, Immunologic; Administration, Oral; Animals; beta-Glucans; Combined Modality Therapy; Humans; Immunotherapy, Adoptive; Mice; Neoplasms; T-Lymphocytes; Tumor Microenvironment

Dietary β-glucans are soluble fibers with potentially health-promoting effects. Gut peptides are important signals in the regulation of energy and glucose homeostasis. This article reviews the effects of different enriched β-glucan food consumption on immune responses, inflammation, gut hormone and cancer. Gut hormones are influenced by enriched β-glucan food consumption and levels of such peptide as YY, ghrelin, glucagon-like peptide 1 and 2 in humans influence serum glucose concentration as well as innate and adaptive immunity. Cancer cell development is also regulated by obesity and glucose dishomeostasy that are influenced by β-glucan food consumption that in turn regulated gut hormones.

Topics: Animals; beta-Glucans; Functional Food; Ghrelin; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Humans; Inflammation; Neoplasms; Peptide YY

Beta-glucans are large polysaccharides produced by a range of prokaryotic and eukaryotic organisms. They have potential immunostimulatory properties and have been used with therapeutic intent as anti-microbial and anti-tumour agents. A range of other potentially beneficial effects have been described, and oral forms of beta-glucans are widely available over-the-counter and online. Parenteral formulations are popular in parts of Asia and are the subject of ongoing trials, worldwide. Beta-glucans are also potential contaminants of pharmaceutical products, and high levels have been described in some blood products. However, little is known about the clinical effects of such contamination, considerable uncertainty exists over the level at which immunostimulation may occur, and there are no guidelines available on acceptable levels. We encountered beta-glucan contamination of one of our products, and we suspect that others may encounter similar issues since the origin of beta-glucan contamination includes commonly used filters and solutions applied in the manufacture of biotherapeutic agents. It is likely that regulators will increasingly enquire about beta-glucan levels in pharmaceutical products, especially those with an immunomodulatory mechanism of action. Here, we review the literature on beta-glucans in pharmaceutical products and propose an acceptable level for therapeutic agents for parenteral use.

Topics: Animals; beta-Glucans; Biosimilar Pharmaceuticals; Clinical Trials as Topic; Humans; Immunomodulation; Neoplasms; Pharmaceutical Preparations; Risk Assessment; Technology, Pharmaceutical

We systematically reviewed and analyzed the available data for galactomannan (GM), β-D-glucan (BG), and polymerase chain reaction (PCR)-based assays to detect invasive fungal disease (IFD) in patients with pediatric cancer or undergoing hematopoietic stem cell transplantation when used as screening tools during immunosuppression or as diagnostic tests in patients presenting with symptoms such as fever during neutropenia (FN). Of 1532 studies screened, 25 studies reported on GM (n = 19), BG (n = 3), and PCR (n = 11). All fungal biomarkers demonstrated highly variable sensitivity, specificity, and positive predictive values, and these were generally poor in both clinical settings. GM negative predictive values were high, ranging from 85% to 100% for screening and 70% to 100% in the diagnostic setting, but failure to identify non-Aspergillus molds limits its usefulness. Future work could focus on the usefulness of combinations of fungal biomarkers in pediatric cancer and HSCT.

Topics: Adolescent; Adult; beta-Glucans; Child; Child, Preschool; Galactose; Hematopoietic Stem Cell Transplantation; Humans; Infant; Infant, Newborn; Invasive Fungal Infections; Mannans; Neoplasms; Polymerase Chain Reaction; Young Adult

Topics: beta-Glucans; Biomarkers; DNA, Fungal; Fungemia; Galactose; Humans; Immunocompromised Host; Mannans; Neoplasms; Sepsis

Pneumocystis jirovecii is the only fungus of its kind to be pathogenic in humans. It is primarily responsible for pneumonia (PJP). The key to understanding immune defences has focused on T-cells, mainly because of the HIV infection epidemic. Patients presenting with PJP all have a CD4 count below 200/mm(3). The introduction of systematic primary prophylaxis and the use of new anti-retroviral drugs have significantly reduced the incidence of this disease in the HIV-infected population, mainly in developed countries. The increasingly frequent use of corticosteroids, chemotherapy, and other immunosuppressive drugs has led to an outbreak of PJP in patients not infected by HIV. These patients presenting with PJP have more rapid and severe symptoms, sometimes atypical, leading to delay the initiation of a specific anti-infective therapy, sometimes a cause of death. However, the contribution of new diagnostic tools and a better understanding of patients at risk should improve their survival.

Topics: Adrenal Cortex Hormones; Antineoplastic Agents; beta-Glucans; Connective Tissue Diseases; Drug Therapy, Combination; Early Diagnosis; HIV Seronegativity; Humans; Immunocompromised Host; Immunologic Deficiency Syndromes; Immunologic Factors; Immunosuppressive Agents; Neoplasms; Organ Transplantation; Pneumocystis carinii; Pneumocystis Infections; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Postoperative Complications; Prognosis; Radiography; Trimethoprim, Sulfamethoxazole Drug Combination

Mushrooms are a highly valuable source of substances that possess unique biological properties and medicinal efficacy. Medicinal mushrooms traditionally have been used to treat cancer, fungal infections, hypertension, diabetes, inflammation, and renal disorders. Medicinal mushrooms produce high-molecular-weight β-glucans, which have antitumor and antifungal activities that stimulate innate immunity. Innate immune cells express pattern recognition receptors (PRRs) such as dectin-1, Toll-like receptors, and mannose receptors on their cell surfaces. These PRRs recognize pathogens by binding to highly conserved pathogen-associated molecular patterns such as β-glucan, mannan, and lipopolysaccharide. The immunomodulating activities of innate immune cells are augmented by the binding of β-glucans to dectin-1 that is expressed by macrophages or dendritic cells. Upon binding β-glucan, innate immune cells activate adaptive immune cells such as B and T lymphocytes or natural killer cells by secreting various cytokines such as interleukins (IL-4, IL-6) and tumor necrosis factor-α. Water-insoluble β-glucans have stronger immunostimulating activities than their water-soluble counterparts. β-glucans have antifungal activity that is similar to their anticancer activities and is mediated by binding to dectin-1, albeit by an unknown mechanism. In this review we discuss recent progress in understanding the mechanisms responsible for the antitumor activities of fungal β-glucans that act through pathogen-associated molecular patterns and PRRs.

Topics: Agaricales; Animals; Antineoplastic Agents, Phytogenic; beta-Glucans; Humans; Immunity, Innate; Lectins, C-Type; Neoplasms; Plant Extracts; Plants, Medicinal; Signal Transduction

β-Glucans are polysaccharides of β-D-glucose extracted from the cell walls of different species of mushrooms, yeast, oat, barley, seaweeds, algae and bacteria. Modern biomedical research has identified β-glucans as biological response modifiers (BRM) with anti-tumor properties that elicit potent immune responses through their recognition by a variety of pattern recognition receptors (PRRs) on dendritic cells (DCs), macrophages and neutrophils. Complement receptor-3 (CR3), lactosylceramides, scavenger receptors and dectin-1 are involved in β-glucan recognition, triggering a series of signaling events that modulate innate and subsequently adaptive immune responses. β-Glucan binding to specific receptors in DCs and macrophages triggers their activation and maturation, increases their antigen-presentation ability and enhances the production of proinflammatory cytokines that stimulate the polarization of TH1 or TH17 responses, and induces the activation of antigen-specific CD8+ cytotoxic T lymphocytes (CTL). Moreover, large β-glucans can be degraded by macrophages into smaller moieties, when released, prime CR3 receptor on neutrophils and natural killer (NK) cells mediating CR3-dependent cellular cytotoxicity (CR3-DCC) of iC3b opsonized tumor cells. Elucidating the molecular mechanisms of β- glucan-induced signaling in immune cells is essential for the design of new therapeutic strategies against cancer. Future studies should be done to translate β-glucan research to the clinic.

Topics: Animals; Antineoplastic Agents, Phytogenic; beta-Glucans; Dendritic Cells; Humans; Neoplasms

Beta-glucans (β-glucans), naturally occurring polysaccharides, are present as constituents of the cell wall of cereal grains, mushrooms, algae, or microbes including bacteria, fungi, and yeast. Since Pillemer et al. first prepared and investigated zymosan in the 1940s and others followed with the investigation of β-glucans in the 1960s and 1970s, researchers have well established the significant role of β-glucans on the immune system relative to cancer treatment, infection immunity, and restoration of damaged bone marrow. However, information on their biological role in anti-metastatic activity remains limited. As an immunomodulating agent, β-glucan acts through the activation of innate immune cells such as macrophages, dendritic cells, granulocytes, and natural killer cells. This activation triggers the responses of adaptive immune cells such as CD4(+) or CD8(+) T cells and B cells, resulting in the inhibition of tumor growth and metastasis. Reports have shown that β-glucans exert multiple effects on cancer cells and cancer prevention. However the mechanisms of their actions appear complex due to differences in source, chemical structure, insufficiently defined preparation, and molecular weight, hence the inconsistent and often contradictory results obtained. This review is focused on the potential of β-glucans as anti-metastatic agents and the known mechanisms underlying their biological effects.

Topics: Animals; beta-Glucans; Clinical Trials as Topic; Humans; Neoplasm Metastasis; Neoplasms; Signal Transduction; Treatment Outcome

β-glucans belong to a group of polysaccharides located in the cell wall of bacteria, fungi including mushrooms, as well as cereals such as barley and oats. All β-glucans are glucose polymers linked together by a (β 1-3) linear β-glycosidic chain core and they differ by their length and branching structures. They are considered biological response modifiers with immunomodulatory and health beneficial effects including anticancer properties. Few studies using purified β- glucans were performed, but their anticancer potential was demonstrated mainly through studies using extracts from mushrooms, yeast or other sources which contain β-glucan as a key component. Their anticancer effects were demonstrated mainly in in vitro and in vivo experimental systems but fewer studies from human populations are available. β-glucans have been used as adjuvant therapy in clinical trials, mainly in the Far East, with a positive effect on patients'survival and quality of life. The mechanism of action is suggested to be through its stimulation of the immune system. This review focuses on human studies; clinical trials and epidemiological data assessing the efficacy and safety of mushroom-derived β- glucans in cancer treatment and prevention. The potential direct effects of β-glucans on cancer cells are also described.

Topics: Agaricales; Animals; Antineoplastic Agents, Phytogenic; beta-Glucans; Clinical Trials as Topic; Humans; Neoplasms; Plant Extracts

It is well established that glucans enhance the efficacy of anti-cancer and anti-infection immunotherapy, both in clinical and experimental conditions. However, the considerable variations among batches of natural glucan in molecular weight, branching frequency, as well as linkage to chitins and mannoproteins, make the clinical applications of natural glucan questionable. The future might be in the use of small synthetic oligosaccharides prepared on the basis of natural glucans. Some of these non natural oligosaccharides showed biological activities such as stimulation of phagocytosis, modulation of gene expression and anti-cancer activity, which were superior to natural glucans. The recent studies strongly suggest the possibility of small chemical changes in the structure of these oligoglucans oriented towards their improved biological activities. This review highlights recent achievements in the immunological effects of synthetic, glucan-based oligosaccharides.

Topics: Animals; Antineoplastic Agents, Phytogenic; beta-Glucans; Humans; Neoplasms; Oligosaccharides; Phagocytosis

Cereal-based food products have been the basis of the human diet since ancient times. Dietary guidelines all over the world are recommending the inclusion of whole grains because of the increasing evidence that whole grains and whole-grain-based products have the ability to enhance health beyond the simple provision of energy and nutrients. In this review we will examine the main chemical components present in whole grains that may have health enhancing properties (dietary fiber, inulin, beta-glucan, resistant starch, carotenoids, phenolics, tocotrienols, and tocopherols) and the role that whole grains may play in disease prevention (cardiovascular diseases and strokes, hypertension, metabolic syndrome, type 2 diabetes mellitus, obesity, as well as different forms of cancer). The knowledge derived from the functional properties of the different chemical components present in whole grains will aid in the formulation and development of new food products with health enhancing characteristics.

Topics: beta-Glucans; Cardiovascular Diseases; Carotenoids; Diabetes Mellitus, Type 2; Diet; Dietary Fiber; Edible Grain; Functional Food; Humans; Hydroxybenzoates; Hypertension; Inulin; Neoplasms; Obesity; Vitamin E

Nonstarch polysaccharides (NSPs) occur naturally in many foods. The physiochemical and biological properties of these compounds correspond to dietary fiber. Nonstarch polysaccharides show various physiological effects in the small and large intestine and therefore have important health implications for humans. The remarkable properties of dietary NSPs are water dispersibility, viscosity effect, bulk, and fermentibility into short chain fatty acids (SCFAs). These features may lead to diminished risk of serious diet related diseases which are major problems in Western countries and are emerging in developing countries with greater affluence. These conditions include coronary heart disease, colo-rectal cancer, inflammatory bowel disease, breast cancer, tumor formation, mineral related abnormalities, and disordered laxation. Insoluble NSPs (cellulose and hemicellulose) are effective laxatives whereas soluble NSPs (especially mixed-link β-glucans) lower plasma cholesterol levels and help to normalize blood glucose and insulin levels, making these kinds of polysaccharides a part of dietary plans to treat cardiovascular diseases and Type 2 diabetes. Moreover, a major proportion of dietary NSPs escapes the small intestine nearly intact, and is fermented into SCFAs by commensal microflora present in the colon and cecum and promotes normal laxation. Short chain fatty acids have a number of health promoting effects and are particularly effective in promoting large bowel function. Certain NSPs through their fermented products may promote the growth of specific beneficial colonic bacteria which offer a prebiotic effect. Various modes of action of NSPs as therapeutic agent have been proposed in the present review. In addition, NSPs based films and coatings for packaging and wrapping are of commercial interest because they are compatible with several types of food products. However, much of the physiological and nutritional impact of NSPs and the mechanism involved is not fully understood and even the recommendation on the dose of different dietary NSPs intake among different age groups needs to be studied.

Topics: beta-Glucans; Blood Glucose; Cardiovascular Diseases; Chemical Phenomena; Cholesterol; Colon; Diabetes Mellitus, Type 2; Diet; Dietary Fiber; Fatty Acids, Volatile; Fermentation; Humans; Insulin; Intestine, Large; Intestine, Small; Neoplasms; Nutritional Status; Polysaccharides; Prebiotics; Starch

Monoclonal antibodies (mAbs) have greatly advanced the field of anti-cancer immunotherapy and have made a major impact in clinical medicine. While more mAbs have been approved by the FDA and entered into the clinical therapeutic arena with indications to treat various solid tumors and hematologic malignancies, extensive efforts have also been made to make mAb therapy more effective. Combination therapy of anti-tumor mAbs with chemotherapeutic drugs has been widely used in the clinical patient care. In addition, many immune stimulating agents have been specifically studied for this very purpose. One compound in particular, β-glucan, has shown very promising and exciting results in pre-clinical animal models and early phase human clinical trials. β-Glucans are naturally occurring, abundant polysaccharides with different structures that can be extracted and purified from fungi, bacteria, oats and barley. The active components of yeast-derived β-glucan exert their unique immune stimulating functions by binding specifically to complement receptor 3 (CR3) via lectin-like domain (LLD) and activating CR3 to promote cellular cytotoxicity of iC3b-coated cancer cells. In addition, particulate yeast-derived β-glucan stimulates both innate and adaptive anti-tumor immune responses. This review covers the anti-cancer mechanisms of anti-tumor mAbs and β-glucans, the pre-clinical studies done with β-glucans in conjunction with anti-tumor mAbs in human carcinoma xenograft models, and the preliminary results of human clinical trials with different β-glucans, as well as those of phase I/II and III studies using the combination of yeast-derived soluble β-glucan and anti-tumor mAbs.

Topics: Animals; Antibodies, Monoclonal; Antibodies, Neoplasm; beta-Glucans; Clinical Trials as Topic; Humans; Immunotherapy; Neoplasms

Beta-glucans participate in the processes of repair, metabolism and detoxification, and affect the overall health of the body counteract the pathological conditions of reactive oxygen and nitrogen and the processes in which they participate. Reactive oxygen species (ROS) and nitrogen (RNS) play an important role in the pathogenesis of many diseases. Production of ROS is an integral part of aerobic metabolism of cells. Physiological concentrations of ROS play an important role in proper functioning of many cellular processes, and their overproduction occurs during induced oxidative stress. Very closely associated with oxidative stress is nitrosative stress. Nitric oxide (NO) reacts with molecular oxygen, superoxide anion radical and metal cations to give more reactive oxygen species. Reactive oxygen and nitrogen react with proteins to cause impairment of their function by oxidation or nitrosylation of amino acid residues, which can direct the path of apoptotic cells. In addition, nitric oxide enhances the effect induced by cyclooxygenase and becomes a mediator of inflammation.

Topics: Animals; beta-Glucans; Humans; Neoplasms; Nitric Oxide; Oxidation-Reduction; Oxidative Stress; Reactive Nitrogen Species; Reactive Oxygen Species; Superoxides

To examine the recent scientific literature on the immune modulating effects of β-glucans and subsequent benefits on infection and cancer.. β-Glucans have been investigated for their ability to protect against infection and cancer and more recently for their therapeutic potential when combined with cancer therapy. Their immune modulating effects are attributed to the ability to bind to pattern recognition receptors including complement receptor 3, scavenger receptors, lactosylceramide, and dectin-1 that results in activation of different aspects of the immune response depending on the cell types and species involved although there is some controversy about the relative importance of each of these receptors. Most of the available evidence comes from preclinical data and human studies are just now beginning to appear in the literature, therefore firm conclusions on its clinical importance cannot yet be made. Perhaps the most promising evidence to date in human trials has come from recent studies on a benefit of β-glucan on quality of life and survival when given in combination with cancer treatment. We identify the need for future studies that compare purified forms of β-glucans from different sources to further the understanding of the mechanisms of action and aid in the development of clinical studies.. β-Glucans appear to be effective at enhancing immune function and reducing susceptibility to infection and cancer. A better understanding of the mechanisms of β-glucan recognition and subsequent immune activation is necessary for the design of effective treatment approaches in future clinical trials.

Topics: Animals; beta-Glucans; Humans; Immune System; Immunologic Factors; Infections; Neoplasms

Beta-glucan is an immuno-stimulating agent that has been used to treat cancer and infectious disease for many years with varying and unpredictable efficacy. Recent studies have unraveled the action mode of yeast-derived beta-glucan in combination with anti-tumor monoclonal antibodies (mAbs) in cancer therapy. It has demonstrated that particulate or large molecular weight soluble beta-glucans are ingested and processed by macrophages. These macrophages secrete the active moiety that primes neutrophil complement receptor 3 (CR3) to kill iC3b-opsonized tumor cells. In vitro and in vivo data demonstrate that successful combination therapy requires complement activation and deposition on tumors and CR3 expression on granulocytes. Pre-clinical animal studies have demonstrated the efficacy of combined beta-glucan with anti-tumor mAb therapy in terms of tumor regression and long-term survival. Clinical trials are underway using anti-epidermal growth factor receptor mAb (cetuximab) in combination with beta-glucan for metastatic colorectal cancer. This review provides a brief overview of this combination therapy in cancer and describes in detail the beta-glucan composition and structure, mechanism of action, and preclinical studies in human carcinoma xenograft models. It is proposed that the addition of beta-glucan will further improve the therapeutic efficacy of anti-tumor mAbs in cancer patients.

Topics: Animals; Antibodies, Monoclonal; Antibodies, Neoplasm; beta-Glucans; Disease Models, Animal; Humans; Immunotherapy; Models, Immunological; Neoplasm Transplantation; Neoplasms; Neutrophils; Saccharomyces cerevisiae; Solubility; Transplantation, Heterologous

The objective of this study was to evaluate the scientific evidence on maitake, including expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing. This review serves as a clinical support tool. Electronic searches were conducted in 10 databases, 20 additional journals (not indexed in common databases), and bibliographies from 50 selected secondary references. No restrictions were placed on the language or quality of the publications. All literature collected pertained to efficacy in humans, dosing, precautions, adverse effects, use in pregnancy and lactation, interactions, alteration of laboratory assays, and mechanisms of action. Standardized inclusion and exclusion criteria were used for selection. Grades were assigned using an evidence-based grading rationale. There was a lack of systematic study on the safety and effectiveness of maitake in humans. However, based on popular use and supportive scientific data, three indications are discussed in this review: cancer, diabetes, and immunostimulation. Despite the lack of scientific evidence, maitake mushroom remains a popular agent in commercial products. Future randomized controlled trials are warranted.

Topics: Adjuvants, Immunologic; Animals; beta-Glucans; Diabetes Mellitus; Food-Drug Interactions; Grifola; Humans; Neoplasms

Non-prescriptional use of medicinal herbs among cancer patients is common around the world. The alleged anti-cancer effects of most herbal extracts are mainly based on studies derived from in vitro or in vivo animal experiments. The current information suggests that these herbal extracts exert their biological effect either through cytotoxic or immunomodulatory mechanisms. One of the active compounds responsible for the immune effects of herbal products is in the form of complex polysaccharides known as beta-glucans. beta-glucans are ubiquitously found in both bacterial or fungal cell walls and have been implicated in the initiation of anti-microbial immune response. Based on in vitro studies, beta-glucans act on several immune receptors including Dectin-1, complement receptor (CR3) and TLR-2/6 and trigger a group of immune cells including macrophages, neutrophils, monocytes, natural killer cells and dendritic cells. As a consequence, both innate and adaptive response can be modulated by beta-glucans and they can also enhance opsonic and non-opsonic phagocytosis. In animal studies, after oral administration, the specific backbone 1-->3 linear beta-glycosidic chain of beta-glucans cannot be digested. Most beta-glucans enter the proximal small intestine and some are captured by the macrophages. They are internalized and fragmented within the cells, then transported by the macrophages to the marrow and endothelial reticular system. The small beta-glucans fragments are eventually released by the macrophages and taken up by other immune cells leading to various immune responses. However, beta-glucans of different sizes and branching patterns may have significantly variable immune potency. Careful selection of appropriate beta-glucans is essential if we wish to investigate the effects of beta-glucans clinically. So far, no good quality clinical trial data is available on assessing the effectiveness of purified beta-glucans among cancer patients. Future effort should direct at performing well-designed clinical trials to verify the actual clinical efficacy of beta-glucans or beta-glucans containing compounds.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; beta-Glucans; Biological Products; Cell Proliferation; Cell Survival; Humans; Immune System; Immunologic Factors; Models, Biological; Neoplasms

beta-Glucans are cell wall constituents of many plants and microorganisms. However, beta-glucans are not expressed on mammalian cells and are recognized as pathogen-associated molecular patterns by pattern recognition receptors. beta-Glucans have been used to treat cancer and infectious disease for many years as biological response modifiers with varying and unpredictable efficacy. Recent studies have demonstrated the mechanism of action of yeast-derived beta-glucan in combination with anti-tumor monoclonal antibodies in cancer therapy. in vitro and in vivo Data indicate that successful combination therapy requires complement activation and iC3b deposition on tumors and complement receptor 3 (CR3) expression on granulocytes. The defined effector cells are CR3(+) neutrophils. This review provides a brief overview of this combination therapy in cancer and describes in detail the beta-glucan composition and receptors, mechanism of action, and preclinical studies in human carcinoma xenograft models. Current and future developments are also discussed to provide our own point of view on this combination therapy in potential clinical investigations. Relevant patents are discussed.

Topics: Animals; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; beta-Glucans; Hematopoiesis; Humans; Immunotherapy; Neoplasms; Transplantation, Heterologous; Yeasts

This review summarizes the recent knowledge about the positive effect of betaglucans on human health. Beta-glucans are polysaccharides occurring in the bran of cereal grains (barley and oats and to a much lesser degree in rye and wheat, in amounts of about 7%, 5%, 2% and less than 1%, respectively), the cell wall of baker's yeast, certain types of fungi, and many kinds of mushrooms. The differences between soluble and insoluble beta-glucans are significant in regards to application, mode of action, and overall biological activity. A growing body of science indicates that beta-glucans promote health in a number of important ways. Beta-glucans have been studied for their hypocholesterolemic effects; these mechanisms include: reducing the intestinal absorption of cholesterol and bile acids by binding to glucans; shifting the liver from cholesterol syntheses to bile acid production; and fermentation by intestinal bacteria to short-chain fatty acids, which are absorbed and inhibit hepatic cholesterol syntheses. Several studies have also shown that oat beta-glucans blunt the glycemic and insulin response. Moreover, beta-1,3-glucans improve the body's immune system defense against foreign invaders by enhancing the ability of macrophages, neutrophils and natural killer cells to respond to and fight a wide range of challenges such as bacteria, viruses, fungi, and parasites. Finally, there is renewed interest in the potential usefulness of beta-glucan as a radioprotective drug for chemotherapy, radiation therapy and nuclear emergencies, particularly because glucan can be used not only as a treatment, but also as a prophylactic.

Topics: Animals; Bacterial Infections; beta-Glucans; Blood Glucose; Cholesterol, LDL; Humans; Hyperlipidemias; Immune System; Insulin; Mice; Neoplasms; Radiation Injuries, Experimental; Triglycerides

Together with chitin, the beta-glucans are components of mycetes' cell walls. A high level of biological efficiency has been found in beta-glucans, especially beta-1,3-D-glucans and beta-1,6-D-glucans isolated from some basidiomycetes. (Biological efficiency refers to the relative ability of beta-glucans to promote a desired response, for example to induce leukocyte activation and to produce inflammatory mediators.) These polysaccharides increase the number of Th1 lymphocytes, which help protect organisms against allergic reactions. A number of beta-glucans, for example pleuran from Oyster (Pleurotus spp.) mushrooms or lentinan from Shiitake (Lentinus edodes) mushrooms, have shown marked anticarcinogenic activity. In addition to having an immunity-stimulating effect, beta-glucans may participate in physiological processes related to the metabolism of fats in the human body. Their application results in a decrease in the total cholesterol content in blood and may also contribute to reductions in body weight.

Topics: Agaricales; Animals; Antineoplastic Agents; Basidiomycota; beta-Glucans; Cell Wall; Humans; Lentinan; Lipid Metabolism; Neoplasms; T-Lymphocytes

Polysaccharides represent the major part of the yeast cell wall dry weight and build the skeletal carcass defining cell wall stability and cell morphology (beta-D-glucans) or constitute amorphous matrix and cell surface fibrous material (mannans and mannoproteins). It is known that yeast cell wall beta-D-glucans reveal immunomodulating properties, which allows for their application in anti-infective and antitumor therapy. Recent data also suggest that polysaccharides reveal antioxidant activity that can result in their protective function as antioxidants, antimutagens, and antigenotoxic agents. The paper provides a review of our continuing research involving water-soluble derivatives of beta-D-glucan isolated from the baker's yeast Saccharomyces serevisiae and of a glucomannan isolated from the industrial yeast Candida utilis. The results are confronted with the available literature data. The derivatives of beta-D-glucan demonstrated potent inhibitory effect on lipid peroxidation comparable to that of the known antioxidants and exerted DNA protection from oxidative damage. The free radical scavenging activity was confirmed by spin-trap electron paramagnetic resonance. Antimutagenic and antigenotoxic activity of the yeast polysaccharides was demonstrated using yeast, bacterial, and algal models. The derivatives of beta-D-glucan exerted potent enhancement of tumor necrosis factor alpha (TNF-alpha) released from murine macrophages and revealed synergistic effect with cyclophosphamide in the treatment of Lewis lung carcinoma and two types of lymphosarcoma in murine models. The results indicate significant protective antioxidant, antimutagenic, and antigenotoxic activities of the yeast polysaccharides and imply their potential application in anticancer prevention/therapy.

Topics: Animals; Anticarcinogenic Agents; Antimutagenic Agents; Antioxidants; beta-Glucans; Candida; Cell Wall; Chemoprevention; Fungal Proteins; Humans; Mannans; Neoplasms; Polysaccharides; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Yeasts

In the last few years, major advances in the treatment of transplant recipients, with hemato-oncological diseases or admitted to the intensive care unit, has been accompanied by an increase in classical fungal infections and by the emergence of uncommon fungal infections. Despite the development of new diagnostic techniques such as galactomannan detection and the availability of new antifungal agents, these opportunistic infections continue to pose a diagnostic challenge, prolong length of hospital stay, and increase costs. In addition, mortality from these infections is high. The present chapter provides a brief review of the epidemiology of these infections, diagnostic advances, and the new antifungal agents that have been developed in the last few years.

Topics: Anidulafungin; Antifungal Agents; Aspergillosis; beta-Glucans; Candidiasis; Clinical Trials as Topic; Critical Care; Diabetes Complications; Disease Susceptibility; Echinocandins; Fungemia; Galactose; Hematologic Diseases; Humans; Immunocompromised Host; Mannans; Meta-Analysis as Topic; Mycoses; Neoplasms; Opportunistic Infections

Management of invasive mold infections in patients with prolonged neutropenia and hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD) has been hampered by the difficulty in diagnosing these infections. Definite diagnosis invariably centers on histologic identification of hyphae in tissue or on culture from a sterile body site. Therefore, most practitioners have relied on prophylaxis and empiric therapy. Currently, emphasis is shifting from routine prophylaxis and empiric therapy to screening of patients with neutropenia at high risk so that clinicians can administer appropriate antifungal therapy early, when it can potentially improve patient outcome. Non-culture-based microbiologic tools are at the forefront of this paradigm shift. Commercially available methods to detect fungal antigens and sophisticated techniques to detect fungal DNA may be used as screening tools during the highest risk period. Together with assessment of clinical signs, cultures, and especially CT scanning, these methods are useful for starting antifungal therapy preemptively. While awaiting further evaluation of these tools during the postengraftment period of allogeneic HSCT, mold-active prophylaxis targeting the subgroup of patients with severe acute or chronic GVHD may be justified. However, some critical issues have not yet been adequately addressed, including the generalizability of study results, impact of mucositis and gastrointestinal GVHD on drug bioavailability, need for therapeutic drug monitoring, impact of prophylaxis on the performance of diagnostic assays, and optimal treatment of breakthrough invasive fungal infections.

Topics: Antifungal Agents; Antigens, Fungal; Aspergillosis; beta-Glucans; Enzyme-Linked Immunosorbent Assay; Humans; Immunocompromised Host; Mycoses; Neoplasms; Neutropenia; Proteoglycans; Risk Assessment; Tomography, X-Ray Computed; Triazoles

Non-cellulosic beta-glucans are now recognized as potent immunological activators, and some are used clinically in China and Japan. These beta-glucans consist of a backbone of glucose residues linked by beta-(1-->3)-glycosidic bonds, often with attached side-chain glucose residues joined by beta-(1-->6) linkages. The frequency of branching varies. The literature suggests beta-glucans are effective in treating diseases like cancer, a range of microbial infections, hypercholesterolaemia, and diabetes. Their mechanisms of action involve them being recognized as non-self molecules, so the immune system is stimulated by their presence. Several receptors have been identified, which include: dectin-1, located on macrophages, which mediates beta-glucan activation of phagocytosis and production of cytokines, a response co-ordinated by the toll-like receptor-2. Activated complement receptors on natural killer cells, neutrophils, and lymphocytes, may also be associated with tumour cytotoxicity. Two other receptors, scavenger and lactosylceramide, bind beta-glucans and mediate a series of signal pathways leading to immunological activation. Structurally different beta-glucans appear to have different affinities toward these receptors and thus generate markedly different host responses. However, the published data are not always easy to interpret as many of the earlier studies used crude beta-glucan preparations with, for the most part, unknown chemical structures. Careful choice of beta-glucan products is essential if their benefits are to be optimized, and a better understanding of how beta-glucans bind to receptors should enable more efficient use of their biological activities.

Topics: Animals; beta-Glucans; Clinical Trials as Topic; Communicable Diseases; Cytokines; Diabetes Mellitus; Fungi; Glucose Metabolism Disorders; Humans; Hypercholesterolemia; Immunologic Factors; Lectins, C-Type; Lymphocytes; Macrophages; Membrane Proteins; Neoplasms; Nerve Tissue Proteins; Phagocytosis; Receptors, Cell Surface; Receptors, Complement; Signal Transduction; T-Lymphocytes, Cytotoxic; Toll-Like Receptor 2

Beta-glucans are naturally occurring polysaccharides. These glucose polymers are constituents of the cell wall of certain pathogenic bacteria and fungi. The healing and immunostimulating properties of mushrooms have been known for thousands of years in the Eastern countries. These mushrooms contain biologically active polysaccharides that mostly belong to group of beta-glucans. These substances increase host immune defense by activating complement system, enhancing macrophages and natural killer cell function. The induction of cellular responses by mushroom and other beta-glucans is likely to involve their specific interaction with several cell surface receptors, as complement receptor 3 (CR3; CD11b/CD18), lactosylceramide, selected scavenger receptors, and dectin-1 (betaGR). beta-Glucans also show anticarcinogenic activity. They can prevent oncogenesis due to the protective effect against potent genotoxic carcinogens. As immunostimulating agent, which acts through the activation of macrophages and NK cell cytotoxicity, beta-glucan can inhibit tumor growth in promotion stage too. Anti-angiogenesis can be one of the pathways through which beta-glucans can reduce tumor proliferation, prevent tumor metastasis. beta-Glucan as adjuvant to cancer chemotherapy and radiotherapy demonstrated the positive role in the restoration of hematopiesis following by bone marrow injury. Immunotherapy using monoclonal antibodies is a novel strategy of cancer treatment. These antibodies activate complement system and opsonize tumor cells with iC3b fragment. In contrast to microorganisms, tumor cells, as well as other host cells, lack beta-glucan as a surface component and cannot trigger complement receptor 3-dependent cellular cytotoxicity and initiate tumor-killing activity. This mechanism could be induced in the presence of beta-glucans.

Topics: Adjuvants, Immunologic; Adult; Agaricales; Angiogenesis Inhibitors; Animals; Antibodies, Monoclonal; beta-Glucans; Humans; Immune System; Immunity; Immunotherapy; Mice; Middle Aged; Neoplasms; Randomized Controlled Trials as Topic; Receptors, Complement

Beta-glucan is a polysaccharide in the form of fiber and the main element of fiber in grains such as barley, oats, yeast and mushrooms. Many studies have examined the efficacy of beta-glucan in terms of the lipid lowering effects, blood sugar reduction, weight reduction, immune modulator, and anticarcinogenic effect. However, there is no comprehensive review article on the biomedical issues regarding beta-glucan. The authors searched for systematic reviews and clinical experiments for each relevant topic and reviewed the biomedical effects of beta-glucan, for the purpose of developing research strategies for the future.

Topics: Animals; Anticholesteremic Agents; beta-Glucans; Blood Glucose; Body Weight; Cholesterol; Dietary Fiber; Dietary Supplements; Dose-Response Relationship, Drug; Humans; Infections; Neoplasms

Beta-glucans, biological response modifiers (BRMs) derived from the cell walls of yeast and other sources, have been demonstrated to prime leukocyte complement receptor 3 (CR3), thus enabling these cells to kill tumours opsonised with complement fragment iC3b. Many tumours activate complement via the classical pathway mediated by antitumour monoclonal antibodies (mAbs) or natural antibodies. Studies into the cellular and molecular mechanisms of action have demonstrated that orally administrated yeast beta-glucans are ingested and processed by macrophages. These macrophages secrete the active moiety that primes neutrophil CR3 to kill iC3b-opsonised tumour cells. Extensive studies in preclinical animal tumour models have demonstrated the efficacy of combined oral particulate yeast beta-glucan with antitumour mAb therapy in terms of tumour regression and long-term survival. It is proposed that the addition of beta-glucan will further improve the clinical therapeutic efficacy of antitumour mAbs in cancer patients.

Topics: Animals; Antibodies, Monoclonal; Antibodies, Neoplasm; beta-Glucans; Humans; Neoplasms; Yeasts

Lentinan is a beta(1-3) glucan clarified to have a life prolonging effect in non-operable, recurrent gastric cancer patients in combination with chemotherapy. The long lasting issue remaining to be resolved has been the ineffectiveness of Lentinan when administered per-orally. Beta(1-3) glucans possess the particulate size around 100-200 microm in aqueous solution which dampered the absorption through abdominal mucosa. Subsequently the particulate size of Lentinan impaired the immunostimulating potency, to induce reductive form of antigen presenting cells, macrophages and dendritic cells relevant for the polarization of Th1/Th2 balance to Th1. The situation is also the case for the clinical benefit of lentinan to reduce the side effect of chemotherapeutic agents such as TS-1, Gemzar, CDDP, known to be a critical dose limiting factor of these agents and to improve quality of life of the patients. Using the modern nano-technology procedures, Mitherapist, containing 15 mg/dl Lentinan, with a particulate size of 0.2 microm able to pass through mucosal barrier was provided. It was found in randomized double blind clinical testing that Mitherapist is effective against allergy by reducing an antigen specific IgE level through polarization to Th1 biased immune response even by per-oral administration. Per oral administration also exhibited the reduced side effect of chemotherapeutic agents such as TS-1, Gemzar, CDDP and greatly improved quality of life of the cancer patients. The role of hypoxia in local neoplastic tissues will be also discussed.

Topics: Adjuvants, Immunologic; Administration, Oral; Antineoplastic Agents; beta-Glucans; Drug Combinations; Humans; Immunotherapy; Lentinan; Neoplasms; Oxonic Acid; Pyridines; Randomized Controlled Trials as Topic; Stomach Neoplasms; Tegafur

Topics: Adjuvants, Immunologic; Animals; Antibodies, Monoclonal; Antibody-Dependent Cell Cytotoxicity; beta-Glucans; Complement Activation; Complement C3b; Complement Membrane Attack Complex; Complement System Proteins; Cytotoxicity, Immunologic; Drug Design; Glucans; Humans; Immunotherapy; Macrophage-1 Antigen; Membrane Proteins; Mice; Models, Immunological; Neoplasm Proteins; Neoplasms; Neoplasms, Experimental

Edible mushrooms are valuable a source of biologically active compounds. Some are used in the prophylaxis and therapy of such diseases as cancer and cardiovascular disease. Their antitumor mechanism is complex. The biologically active substances in mushrooms decrease DNA damage, reduce carcinogen concentrations and their activation, inhibit the growth of cancer cells by scavenging free radicals, stimulate the immune system, and induce tumor cell apoptosis. The stimulation of the immune system by the biologically active compounds in edible mushrooms protects against cold, flu, infections, well as AIDS by inhibition of viral replication. Mushrooms contain effective substances which decrease the LDL fraction of cholesterol in blood. They also prevent the accumulation of serum triaclyglycerols, thus decreasing the risk of developing cardiovascular disease. The therapeutic properties of mushrooms result from the specific polysaccharides, such as beta-glucans and chitosans, that are present in the fructification of fungi.

Topics: Adjuvants, Immunologic; Agaricales; Anticholesteremic Agents; Antineoplastic Agents; beta-Glucans; Cardiovascular Diseases; Chitosan; Cholesterol, LDL; Free Radicals; Humans; Neoplasms; Nutritive Value; Phytotherapy; Plant Preparations; Polysaccharides

Maitake mushroom (Grifola frondosa) MD-fraction containing beta-1,6 glucan with beta-1,3 branched chains has previously exhibited strong anticancer activity by increasing immune-competent cell activity.1,2 In this non-random case series, a combination of MD-fraction and whole maitake powder was investigated to determine its effectiveness for 22- to 57-year-old cancer patients in stages II-IV. Cancer regression or significant symptom improvement was observed in 58.3 percent of liver cancer patients, 68.8 percent of breast cancer patients, and 62.5 percent of lung cancer patients. The trial found a less than 10-20 percent improvement for leukemia, stomach cancer, and brain cancer patients. Furthermore, when maitake was taken in addition to chemotherapy, immune-competent cell activities were enhanced 1.2-1.4 times, compared with chemotherapy alone. Animal studies have supported the use of maitake MD-fraction for cancer.

Topics: Adult; Agaricales; Animals; Antibiotics, Antineoplastic; beta-Glucans; Breast Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Squamous Cell; Dose-Response Relationship, Drug; Female; Glucans; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasms

Maitake (Grifola frondosa) is the Japanese name for an edible fungus with a large fruiting body characterized by overlapping caps. It is a premier culinary as well as medicinal mushroom. Maitake is increasingly being recognized as a potent source of polysaccharide compounds with dramatic health-promoting potential. The most recent development is the MD-fraction, a proprietary maitake extract its Japanese inventors consider to be a notable advance upon the preceding D-fraction. The D-fraction, the MD-fraction, and other extracts, often in combination with whole maitake powder, have shown particular promise as immunomodulating agents, and as an adjunct to cancer and HIV therapy. They may also provide some benefit in the treatment of hyperlipidemia, hypertension, and hepatitis.

Topics: Adjuvants, Immunologic; Administration, Oral; Animals; Anti-HIV Agents; Antibiotics, Antineoplastic; beta-Glucans; Body Weight; Drug Administration Schedule; Glucans; HIV Infections; Humans; Hyperlipidemias; Hypertension; Hypolipidemic Agents; Liver Diseases; Neoplasms; Polyporaceae

Medicinal properties have been attributed to mushrooms for thousands of years. Mushroom extracts are widely sold as nutritional supplements and touted as beneficial for health. Yet, there has not been a critical review attempting to integrate their nutraceutical potential with basic science. Relatively few studies are available on the biologic effects of mushroom consumption, and those have been performed exclusively in murine models. In this paper, we review existing data on the mechanism of whole mushrooms and isolated mushroom compounds, in particular (1-->3)-beta-D-glucans, and the means by which they modulate the immune system and potentially exert tumor-inhibitory effects. We believe that the antitumor mechanisms of several species of whole mushrooms as well as of polysaccharides isolated from Lentinus edodes, Schizophyllum commune, Grifola frondosa, and Sclerotinia sclerotiorum are mediated largely by T cells and macrophages. Despite the structural and functional similarities of these glucans, they differ in their effectiveness against specific tumors and in their ability to elicit various cellular responses, particularly cytokine expression and production. Unfortunately, our data base on the involvement of these important mediators is still rather limited, as are studies concerning the molecular mechanisms of the interactions of glucans with their target cells. As long as it remains unclear what receptors are involved in, and what downstream events are triggered by, the binding of these glucans to their target cells, it will be difficult to make further progress in understanding not only their antitumor mechanisms but also their other biological activities.

Topics: Adjuvants, Immunologic; Agaricales; Animals; Antineoplastic Agents; beta-Glucans; Dextranase; Dietary Supplements; Glucans; Humans; Lentinan; Macrophages; Mice; Monocytes; Neoplasms; Sizofiran; T-Lymphocytes

Imprime PGG (Imprime) is an i.v. administered, yeast β-1,3/1,6 glucan in clinical development with checkpoint inhibitors. Imprime-mediated innate immune activation requires immune complex formation with naturally occurring IgG anti-β glucan Abs (ABA). We administered Imprime to healthy human volunteers to assess the necessity of ABA for Imprime-mediated immunopharmacodynamic (IPD) changes. Imprime (4 mg/kg) was administered i.v. in single and multiple infusions. Subsets of subjects were premedicated with antihistamine and corticosteroid. Peripheral blood was measured before, during and after Imprime administration for IPD changes (e.g., ABA, circulating immune complexes, complement activation, complete blood counts, cytokine/chemokine, and gene expression changes). IPD changes were analyzed based on pretreatment serum ABA levels: low-ABA (<20 μg/ml), mid-ABA (≥20-50 μg/ml), and high-ABA (≥50 μg/ml). At the end of infusion, free serum ABA levels decreased, circulating immune complex levels increased, and complement activation was observed. At ∼1-4 h after end of infusion, increased expression of cytokines/chemokines, a 1.5-4-fold increase in neutrophil and monocyte counts and a broad activation of innate immune genes were observed. Low-ABA subjects typically showed minimal IPD changes except when ABA levels rose above 20 μg/ml after repeated Imprime dosing. Mild-to-moderate infusion-related reactions occurred in subjects with ABA ≥20 μg/ml. Premedications alleviated some of the infusion-related reactions, but also inhibited cytokine responses. In conclusion, ABA levels, being critical for Imprime-mediated immune activation may provide a plausible, mechanism-based biomarker to identify patients most likely to respond to Imprime-based anticancer immunotherapy.

Topics: Adjuvants, Immunologic; Antibodies, Fungal; beta-Glucans; Chemokines; Female; Fungal Polysaccharides; Humans; Immunotherapy; Male; Neoplasms; Saccharomyces cerevisiae

Beta-(1,3)/(1,6) D-glucan, a component of the fungal cell wall, has been shown to stimulate the immune system, enhance hematopoiesis, amplify killing of opsonized tumor cells and increase neutrophil chemotaxis and adhesion. In view of these attributes, the beta-glucans should be studied for both their therapeutic efficacy in patients with cancer as well as an adjunctive therapy in patients receiving chemotherapy as a maneuver to limit suppression of hematopoiesis.In this study, twenty patients with advanced malignancies receiving chemotherapy were given a beta-(1,3)/(1,6) D-glucan preparation (MacroForce plus IP6, ImmuDyne, Inc.) and monitored for tolerability and effect on hematopoiesis. Our results lead us to conclude that beta-glucan is well-tolerated in cancer patients receiving chemotherapy, may have a beneficial effect on hematopoiesis in these patients and should be studied further, especially in patients with chronic lymphocytic leukemia and lymphoma.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; beta-Glucans; Female; Hematopoiesis; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma; Male; Middle Aged; Neoplasms; Proteoglycans

Innate immune cells are critical in antitumor immune surveillance and the development of antitumor adaptive cellular immunity. Trained innate immune cells demonstrate immune memory-like characteristics, producing more vigorous immune responses to secondary homologous or heterologous stimuli. This study aimed to investigate whether inducing trained immunity is beneficial when using a tumor vaccine to promote antitumor adaptive immune responses. A biphasic delivery system was developed with the trained immunity inducer Muramyl Dipeptide (MDP) and specific tumor antigen human papillomavirus (HPV) E7 peptide encapsulated by poly(lactide-co-glycolide)-acid(PLGA) nanoparticles (NPs), and the NPs along with another trained immunity agonist, β-glucan, were further embedded in a sodium alginate hydrogel. The nanovaccine formulation demonstrated a depot effect for E7 at the injection site and targeted delivery to the lymph nodes and dendritic cells (DCs). The antigen uptake and maturation of DCs were significantly promoted. A trained immunity phenotype, characterized by increased production of IL-1β, IL-6, and TNF-α, was induced in vitro and in vivo in response to secondary homologous or heterologous stimulation. Furthermore, prior innate immune training enhanced the antigen-specific INF-γ-expressing immune cell response elicited by subsequent stimulation with the nanovaccine. Immunization with the nanovaccine completely inhibited the growth of TC-1 tumors and even abolished established tumors in mice. Mechanistically, the inclusion of β-glucan and MDP significantly enhanced the responses of tumor-specific effector adaptive immune cells. The results strongly suggest that the controlled release and targeted delivery of an antigen and trained immunity inducers with an NP/hydrogel biphasic system can elicit robust adaptive immunity, which provides a promising tumor vaccination strategy.

Topics: Adjuvants, Immunologic; Animals; beta-Glucans; Cancer Vaccines; Humans; Hydrogels; Immunization; Mice; Neoplasms

β-Glucan from Lentinus edodes (LNT), an edible mushroom, possesses strong anticancer activity. However, the therapeutic effects of LNT during the occurrence and progression of breast cancer and their underlying molecular mechanisms have not been elucidated.. Mouse mammary tumor virus-polyoma middle tumor-antigen (MMTV-PyMT) transgenic mice were used as a breast cancer mouse model. Hematoxylin and eosin, immunohistochemical, and immunofluorescence staining were performed for histopathological analysis. Moreover, we developed an inflammatory cell model using tumor necrosis factor-α (TNF-α). Macrophage polarization was assessed using western blot analysis and immunofluorescence.. Orphan nuclear receptor 77 (Nur77) and sequestosome-1 (p62) were highly expressed and positively correlated with each other in breast cancer tissues. LNT significantly inhibited tumor growth, ameliorated inflammatory cell infiltration, and induced tumor cell apoptosis in PyMT transgenic mice. Moreover, LNT attenuated the ability of tumors to metastasize to lung tissue. Mechanistically, LNT treatment restrained macrophage polarization from M1 to M2 phenotype and promoted autophagic cell death by inhibiting Nur77 expression, AKT/mTOR signaling, and inflammatory signals in breast tumor cells. However, LNT did not exhibit a direct pro-autophagic effect on tumor cell death, except for its inhibitory effect on Nur77 expression. LNT-mediated autophagic tumor cell death depends on M1 macrophage polarization. In in vitro experiments, LNT inhibited the upregulation of p62, autophagy activation, and inflammatory signaling pathways in Nur77 cells.. LNT inhibited macrophage M2 polarization and subsequently blocked the AKT/mTOR and inflammatory signaling axes in breast cancer cells, thereby promoting autophagic tumor cell death. Thus, LNT may be a promising therapeutic strategy for breast cancer.

Topics: Animals; Autophagy; beta-Glucans; Macrophages; Mice; Mice, Transgenic; Neoplasms; Proto-Oncogene Proteins c-akt; Shiitake Mushrooms; TOR Serine-Threonine Kinases

Induction of cellular immunity is important for effective cancer immunotherapy. Although various antigen carriers for cancer immunotherapy have been developed to date, balancing efficient antigen delivery to antigen presenting cells (APCs) and their activation

Topics: Animals; Antigen-Presenting Cells; beta-Glucans; Biocompatible Materials; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Cytokines; Female; Hydrogen-Ion Concentration; Immunity, Cellular; Immunotherapy; Liposomes; Macrophage Activation; Mice; Mice, Inbred C57BL; Neoplasms; Ovalbumin; Tumor Microenvironment

Dendritic cells (DCs) are recognized as the most potent antigen-presenting cells, capable of priming both naïve and memory T cells. Thus, tumor-resident DCs (tumor-associated DCs: TADCs) play a crucial role in the immune response against tumors. However, TADCs are also well known as a "double-edged sword" because an immunosuppressive environment, such as a tumor microenvironment, maintains the immature and tolerogenic properties of TADCs, resulting in the deterioration of the tumor. Therefore, it is essential to maintain and enhance the anti-tumoral activity of TADCs to aid tumor elimination. This study demonstrated the potential for tumor growth inhibition of Aureobasidium pullulan-derived β-glucan (AP-BG). Administration of AP-BG dramatically limited the development of different types of tumor cell lines transplanted into mice. Examination of the tumor-infiltrating leukocytes revealed that AP-BG caused high expression of co-stimulatory molecules on TADCs and enhanced the production of cytolytic granules as well as pro-inflammatory cytokines by the tumor-resident T cells. Furthermore, the syngeneic mixed lymphoid reaction assay and popliteal lymph node assay showed the significant ability of AP-BG to improve DCs' antigen-specific priming of T cells in vitro and in vivo. Taken together, β-glucan might be an immune-potentiating adjuvant for cancer treatment. This highly widely-used reagent will initiate a new way to activate DC-targeted cancer immune therapy.

Topics: Adjuvants, Immunologic; Animals; Aureobasidium; beta-Glucans; Cell Line, Tumor; Dendritic Cells; Disease Models, Animal; Drug Screening Assays, Antitumor; Humans; Lymphocyte Activation; Lymphocytes, Tumor-Infiltrating; Mice; Mice, Transgenic; Neoplasms; T-Lymphocytes; Tumor Microenvironment

Cisplatin exhibits a sufficient killing effect on cancer cells; however, it damages normal cells simultaneously. Herein, we developed a prodrug delivery system based on branched β-(1→3)-d-glucan. This natural biomacromolecule-based polysaccharide nanotube was modified with cisplatin embedded in the hollow cavity (BFCP), showing high anticancer activity and low toxicity

Topics: Animals; Antineoplastic Agents; Apoptosis; beta-Glucans; Cell Line; Cisplatin; Drug Delivery Systems; Humans; Mice, Nude; Nanotubes; Neoplasms; Polysaccharides; Prodrugs

Curdlan activates dendritic cells (DCs) and enhances DC-based antitumor immunity. However, hydrophobicity and heterogeneity of curdlan particulates hinder perfect binding of curdlan to dectin-1 receptor, resulting in the reduced activation of antigen presenting cells and limited antitumor effects. Herein, we synthesized partially oxidized curdlan derivative (β-1,3-polyglucuronic acid, denote PGA). PGA-45 polymer, the reaction product prepared from curdlan by oxidation with 4-acetamido-TEMPO/NaClO/NaClO

Topics: Adjuvants, Immunologic; Animals; Antineoplastic Agents; beta-Glucans; Cell Line, Tumor; Cell Proliferation; Cytokines; Dendritic Cells; Humans; Immunity; Immunotherapy; Lectins, C-Type; Mice; Mice, Inbred C57BL; Neoplasms; Oxidation-Reduction; Polymers; T-Lymphocytes; Toll-Like Receptor 4

Non-HIV immunocompromised patients with Pneumocystis jirovecii pneumonia (PCP) have lower fungal load than those with AIDS, potentially affecting the accuracy of diagnostic biomarkers. Therefore, we investigated the performance of serum (1,3)-Beta-d-Glucan (BDG) in conjunction with quantitative Pneumocystis jirovecii PCR (qPCR) in non-HIV cancer patients.. We reviewed records of non-HIV cancer patients and classified them as definite, probable, or possible PCP cases, according to clinicoradiological features, microscopy findings, and qPCR results in bronchoscopy specimens. We evaluated the diagnostic performance of serum BDG and its correlation with qPCR results.. We identified 101 PCP patients (73 definite/probable, 28 possible) and 74 controls. Correlation of BDG and qPCR was low among all 101 qPCR-positive patients (Spearman's = 0.38) and in definite/probable PCP cases (Spearman's = 0.18). Considering all qPCR-positive patients, BDG showed consistently low sensitivity at different cutoffs. Among definite/probable cases, the diagnostic accuracy of BDG remained poor, yet slightly improved with high qPCR thresholds (AUC = 0.86 at ≥2000 DNA copies/mL). BDG had a low PPV but excellent NPV across different qPCR and BDG cutoffs.. BDG and qPCR levels correlate poorly in non-HIV cancer patients with PCP. BDG diagnostic performance is suboptimal but a negative test may be useful to rule out PCP in this population.

Topics: beta-Glucans; Humans; Neoplasms; Pneumocystis carinii; Pneumonia, Pneumocystis; Proteoglycans; Sensitivity and Specificity

Trained innate immunity, induced via modulation of mature myeloid cells or their bone marrow progenitors, mediates sustained increased responsiveness to secondary challenges. Here, we investigated whether anti-tumor immunity can be enhanced through induction of trained immunity. Pre-treatment of mice with β-glucan, a fungal-derived prototypical agonist of trained immunity, resulted in diminished tumor growth. The anti-tumor effect of β-glucan-induced trained immunity was associated with transcriptomic and epigenetic rewiring of granulopoiesis and neutrophil reprogramming toward an anti-tumor phenotype; this process required type I interferon signaling irrespective of adaptive immunity in the host. Adoptive transfer of neutrophils from β-glucan-trained mice to naive recipients suppressed tumor growth in the latter in a ROS-dependent manner. Moreover, the anti-tumor effect of β-glucan-induced trained granulopoiesis was transmissible by bone marrow transplantation to recipient naive mice. Our findings identify a novel and therapeutically relevant anti-tumor facet of trained immunity involving appropriate rewiring of granulopoiesis.

Topics: Adaptive Immunity; Adoptive Transfer; Animals; beta-Glucans; Epigenesis, Genetic; Granulocytes; Immunity, Innate; Interferon Type I; Mice, Inbred C57BL; Monocytes; Neoplasms; Neutrophils; Phenotype; Receptor, Interferon alpha-beta; Transcription, Genetic; Transcriptome

A long-anticipated cancer therapy would deliver the right type of therapeutic agents to the target in control with minimal systemic toxicity. The purpose of this study was to prepare lactosylated curdlan-triornithine nanocarriers (CTOLs), and target deliver gene to hepatoma cells. Structures and biophysical properties had been elucidated with physical and chemical methods. The results revealed that those functionalized polymers can completely condense the gene into spherical nanoparticles. Cytotoxicity assay, GFP-pDNA and siRNA transfection in vitro were implemented successively. Observations showed that CTOL 20% with the highest lactose acid substitution degree targeted delivered gene into HepG2 cells over expressing ASGPR receptors and had pretty gene knockdown efficiency over 70%. Meanwhile, the carriers showed excellent biocompatibility. Our studies demonstrated that CTOLs with lower toxicity and higher gene binding capacity may serve as a potential valuable platform that can be tailored to target the liver cancer cells for therapeutic gene.

Topics: beta-Glucans; DNA; Drug Carriers; Drug Delivery Systems; Gene Targeting; Gene Transfer Techniques; Genetic Therapy; Hep G2 Cells; Humans; Nanoparticles; Neoplasms; RNA, Small Interfering

Immuno-therapies are gaining more importance to treat certain forms of cancer. The goal of therapies is to enhance person's own IgG, IgA, IgM, IgD, IgE and macrophages to combat with neoplastic cells hence the effectiveness of the immune system. Since, early civilization mushrooms are considered as potent food as well as medicine. Mushrooms are well known for their bioactive compounds such as chizophyllan, lentinan, grifolan, PSP (polysaccharide-peptide complex) and PSK (polysaccharide-protein complex) which are considered as medicines against melignancy. They prevent oncogenesis by the direct effect on tumor metastasis and exhibits antitumor effects by the induction of immune response in host. Mushroom polysaccharides have promising future for treatment of cancers due to their mode of action and efficacy. Also there are some hurdles during this treatment, but it will start a new era of safer and effective medicine based on mushroom polysaccharides.

Topics: Agaricales; Animals; Antineoplastic Agents; beta-Glucans; Humans; Immunologic Factors; Immunotherapy; Lentinan; Neoplasms; Polysaccharides; Proteoglycans

Serum (1,3)-beta-D glucan (BDG) is increasingly used to guide the management of suspected Pneumocystis pneumonia (PCP). BDG lacks specificity for PCP, and its clinical performance in high-risk cancer patients has not been fully assessed. Polymerase chain reaction (PCR) for PCP detection is highly sensitive, but cannot differentiate between colonization and infection. We evaluated the diagnostic performance of serum BDG in conjunction with PCP PCR on respiratory samples in patients with cancer and unexplained lung infiltrates.. We performed a retrospective analysis of adult patients evaluated for PCP at our institution from 2012 to 2015, using serum BDG and PCP PCR. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the serum BDG at different thresholds were evaluated using PCP PCR alone or in conjunction with clinical presentation in PCP PCR-positive patients.. With PCP PCR alone as the reference method, BDG (≥80 pg/mL) had a sensitivity of 69.8%, specificity of 81.2%, PPV of 34.6%, and NPV of 95.2% for PCP. At ≥200 pg/mL in patients with a positive PCR and a compatible PCP clinical syndrome, BDG had a sensitivity of 70%, specificity of 100%, PPV of 100%, and NPV of 52.0% for PCP.. Patients negative by both BDG and PCR were unlikely to have PCP. In patients with a compatible clinical syndrome for PCP, higher BDG values (>200 pg/mL) were consistently associated with clinically-significant PCP infections among PCP PCR-positive oncology patients.

Topics: beta-Glucans; DNA, Fungal; Female; Humans; Male; Middle Aged; Neoplasms; Pneumocystis carinii; Pneumonia, Pneumocystis; Real-Time Polymerase Chain Reaction; Reproducibility of Results; Retrospective Studies; Sensitivity and Specificity

Topics: beta-Glucans; Humans; Neoplasms; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction

β-glucans trigger the proinflammatory responses of innate immune cells to enhance the host defense. A variety of β-glucans were identified as strong immune stimulator and exerted antitumor activities. Our previous work indicates that a β-1,3/1,6-glucan (BG136) derived from marina alga Durvillaea antarctica promotes the proinflammatory responses in macrophage cell line RAW264.7. In the present study, we further explored its antitumor effects in vivo as an immune stimulator. The data shows that BG136 alone decreases the tumor burdens in DLD1 xenograft and AOM-DSS induced tumor models. BG136 also augments the antitumor effects of PD-1 antibody in B16 syngeneic tumor model. BG136 increases macrophage phagocytosis, enhances cytokine/chemokine secretion and modulates the systemic and intratumoral immune cell composition. Collectively, these data suggest that BG136 might act as an immune stimulator to exert antitumor effects in vivo.

Topics: Adjuvants, Immunologic; Animals; Cell Line, Tumor; Cytokines; Glucans; Humans; Macrophages; Mice; Mice, Inbred C57BL; Neoplasms; Phaeophyceae; Phagocytosis; Programmed Cell Death 1 Receptor; Xenograft Model Antitumor Assays

In this study, negatively charged carboxylic curdlan (Cc) bearing a β-1,3-polyglucuronic acid structure was employed to fabricate nanosized polyelectrolyte complexes (PECs) with positively charged chitosan (CS) in aqueous solution as potential carriers for 5-fluorouracil (5Fu) delivery. Nanosized CS/Cc PECs were formed by the addition of 0.5mg/mL solutions of CS and Cc with a mixing ratio of 1:1 (w/w) at pH 3.0. Under optimized conditions, the prepared CS/Cc PECs showed spherical morphology with an average size of about 180nm and a zeta potential of around 41mV. The 5Fu drug was incorporated into the nanosized CS/Cc PECs and showed excellent encapsulation efficiency (86.47%) and loading content (10.81%). The drug release data in vitro indicated that the nanosized CS/Cc PECs are promising carriers for the sustained release of 5Fu with an anomalous transport mechanism following the Ritger-Peppas model. Besides, the CS/Cc PECs exhibited low cytotoxic activity against SPCA-1 and HeLa cell lines in vitro. This finding suggested that the development of the nanosized CS/Cc PECs offered great promise as an antitumor drug platform.

Topics: beta-Glucans; Chitosan; Drug Carriers; Fluorouracil; HeLa Cells; Humans; Nanoparticles; Neoplasms; Polyelectrolytes

Cancer incidence continues to be a major health problem possibly because cancer is a complex system comprising many agents that interact in a non-linear manner resulting in many possible outcomes. The degree of complexity of a cancer system could be vast involving multiple endogenous and exogenous agents interacting with the over 10 trillion cells comprising the body. It is hypothesized that the practical management of this complexity may be a key to cancer prevention and possibly treatment. But the management and resolution of such an immensely complex system is difficult and may require a multidisciplinary approach including physics, biology, biochemistry and medical science. Research such as in systems biology involving large data sets may offer resolution in time, but the scale of the task is daunting. In evaluating the hypothesis, this paper proposes a method of resolution of the complex cancer system through a proxy in the form of the vital body system, energy balance, involved in several cancer processes. Although I suggest that the energy balance system is itself complex, it may permit access to factors that may be used in limiting cancer initiation. Meta-analysis related to factors of blood sugar, inflammation, stress and immune response reveal that they could be likely candidates for management. Analysis also reveals certain devices that may give practical effect to these management options. Due to the inherent complexity of a cancer system, multiple devices may need to be applied in a combination. The analysis suggests that the low-risk and low-cost devices metformin, vitamin D and vitamin C, may prove to be suitable for use as a practical cancer prevention strategy. If the presented hypothesis is correct, a practical method for prevention or management of cancer may be possible. A trial to test the hypothesis is proposed.

Topics: beta-Glucans; Decision Support Techniques; Diet; Drug Synergism; Energy Metabolism; Exercise; Glucose; Homeostasis; Humans; Inflammation; Melatonin; Meta-Analysis as Topic; Metformin; Models, Biological; Neoplasms; Stress, Physiological; Systems Theory; Vitamins

Water-soluble β-1,3-glucan (w-glucan) prepared from curdlan is reported to possess various bioactive and medicinal properties. To develop an efficient and cost-effective microbial fermentation method for the direct production of w-glucan, a coupled fermentation system of Agrobacterium sp. and Trichoderma harzianum (CFS-AT) was established. The effects of Tween-80, glucose flow rate, and the use of a dissolved oxygen (DO) control strategy on w-glucan production were assessed. The addition of 10 g L

Topics: Agrobacterium; Antineoplastic Agents; beta-Glucans; Cell Line, Tumor; Fermentation; Glucose; Humans; Hydrolysis; Industrial Microbiology; Neoplasms; Oxygen; Polysorbates; Solubility; Trichoderma; Water

In this work, a nano-in-micro carrier was constructed by loading polymer-lipid hybrid nanoparticles (NPs) into porous and hollow yeast cell wall microparticles (YPs) for macrophage-targeted oral delivery of cabazitaxel (CTX). The YPs, primarily composed of natural β-1,3-d-glucan, can be recognized by the apical membrane receptor, dectin-1, which has a high expression on macrophages and intestinal M cells. By combining electrostatic force-driven self-deposition with solvent hydration/lyophilization methods, the positively charged NPs loaded with CTX or fluorescence probes were efficiently packaged into YPs, as verified by scanning electron microscope (SEM), atomic force mircoscope (AFM), and confocal laser scanning microscopy (CLSM) images. NP-loaded YPs (NYPs) showed a slower in vitro drug release and higher drug stability compared with NPs in a simulated gastrointestinal environment. Biodistribution experiments confirmed a widespread distribution and extended retention time of NYPs in the intestinal tract after oral administration. Importantly, a large amount of NYPs were primarily accumulated and transported in the intestinal Peyer's patches as visualized in distribution and absorption site studies, implying that NYPs were mainly absorbed through the lymphatic pathway. In vitro cell evaluation further demonstrated that NYPs were rapidly and efficiently taken up by macrophages via receptor dectin-1-mediated endocytosis using a mouse macrophage RAW 264.7 cell line. As expected, in the study of in vivo pharmacokinetics, the oral bioavailability of CTX was improved to 32.1% when loaded in NYPs, which is approximately 5.7 times higher than that of the CTX solution, indicating the NYPs are efficient for oral targeted delivery. Hence, this nano-in-micro carrier is believed to become a hopeful alternative strategy for increasing the oral absorption of small molecule drugs.

Topics: Administration, Oral; Animals; Antineoplastic Agents; beta-Glucans; Biological Availability; Cell Wall; Delayed-Action Preparations; Drug Carriers; Drug Liberation; Drug Screening Assays, Antitumor; Intestinal Absorption; Macrophages; Male; Mice; Models, Animal; Nanoparticles; Neoplasms; Particle Size; Proteoglycans; Rats; Rats, Sprague-Dawley; RAW 264.7 Cells; Saccharomyces cerevisiae; Taxoids; Tissue Distribution

The development of environmentally responsive drug delivery systems for the treatment of cancer has attracted particular interest in recent years. However, the enhancement of drug loading capacity and realization of pH-responsive drug delivery remain challenging. Herein, we employ carboxymethyl curdlan as a hydrophilic carrier to wrap doxorubicin (DOX) directly via electrostatic interaction. The sizes of the formed nanoparticles can be simply tuned by changing their feeding ratios. In particular, the nanoparticles are highly stable in aqueous solution without size variation. In vitro drug release and cytotoxicity assays illustrate that this delivery system can release DOX differentially under various environmental conditions and transport it into cell nuclei efficiently, with comparable therapeutic effect to the free drug. These results suggest that the carrying of antitumor drugs by polysaccharide via electrostatic interaction is a simple but effective way to construct a pH-dependent drug delivery platform.

Topics: beta-Glucans; Delayed-Action Preparations; Doxorubicin; HeLa Cells; Humans; Hydrogen-Ion Concentration; Neoplasms; Static Electricity

Naturally occurring β-glucans have been widely regarded as a natural source for functional foods and pharmaceuticals due to their immunomodulatory property and antitumor activity. However, physicochemically stable and biocompatible β-glucans are rarely explored as a carrier for nanomaterials to overcome the problems of aggregation and nanotoxicity. Here, we developed highly stable and biocompatible mushroom β-glucan coated gold nanorods (AuNR-Glu) for cancer photothermal therapy by integrating Pleurotus tuber-regium sclerotial β-glucan (Glu) and plasmonic gold nanorods (AuNRs) possessing photothermal property in the second near-infrared (NIR-II) window. AuNR-Glu showed high colloidal stability in various biological media, even in simulated gastric fluid. Moreover, AuNR-Glu had low cytotoxicity and high photothermal stability, which are excellent characteristics for photothermal agents for cancer therapy. In vitro experiments showed that AuNR-Glu nanohybrid was effective against MCF-7 (only 4.5 ± 0.9% viability) at a low dose of 20 μg/mL under NIR-II at a safe laser power density (0.75 W/cm

Topics: beta-Glucans; Cell Line, Tumor; Cell Survival; Gold; Humans; Nanotubes; Neoplasms; Phytotherapy; Plant Extracts; Pleurotus

Limited specific data and investigations are available for the diagnosis of Invasive Fungal Infection (IFI) in paediatrics cancer patients. Three non-invasive tests; Platelia Aspergillus EIA for galactomannan (GM), β-D-glucan (BDG) assay and pan-fungal real-time PCR for fungal DNA in blood were evaluated. One hundred twenty-five paediatrics cancer patients at the high risk of IFI were enrolled. Single blood and serum samples were evaluated by all the three methods. Patients were classified into 10 proven, 52 probable and 63 no IFI cases in accordance with EORTC MSG 2008 revised guidelines. The sensitivity, specificity, PPV and NPV of all the three tests in proven, probable and no IFIs cases were analysed singly and in combination. The sensitivity, specificity, PPV and NPV of GM, BDG and pan-fungal real-time PCR were: 87%, 61%, 81%, 69.5% for GM, 88%, 59.5%, 81%, 71.4% for BDG and 89%, 69.2%, 85%, 67.5% for PCR (95% CI). Among different combinations, best combination was found to be GM and PCR with sensitivity, specificity, PPV and NPV of 98.2%, 89.3%, 97.1% and 90% respectively. Single samples must be evaluated by combination of tests.

Topics: Adolescent; Antigens, Fungal; beta-Glucans; Child; Child, Preschool; DNA, Fungal; Fungi; Galactose; Humans; Immunoassay; Infant; Invasive Fungal Infections; Male; Mannans; Neoplasms; Patients; Real-Time Polymerase Chain Reaction; Sensitivity and Specificity

Cancer vaccine has the ability to directly eradicate tumor cells by creating and activating cytotoxic T lymphocytes (CTLs). To achieve efficient CTL activity and to induce Th1 responses, it is essential to administer an appropriate adjuvant as well as an antigen. CpG-ODN is known as a ligand of Toll-like receptor 9 (TLR9) and strongly induces Th1 responses. In our previous study, we developed a CpG-ODN delivery system by use of the formation of complexes between ODN and a β-glucan SPG, denoted as CpG/SPG, and demonstrated that CpG/SPG induces high Th1 responses. In this study, we created a nanogel made from CpG/SPG complexes through DNA-DNA hybridization (cross-linked (CL)-CpG). Immunization with CL-CpG induced much stronger antigen-specific Th1 responses in combination with the antigenic protein ovalbumin (OVA) than that with CpG/SPG. Mice preimmunized with CL-CpG and OVA exhibited a long delay in tumor growth and an improved survival rate after tumor inoculation. These immune inductions can be attributed to the improvement of cellular uptake by the combination of increased size and the cluster effect of the β-glucan recognition site in the nanogel structure. In other words, the particle nature of CL-CpG, instead of the semiflexible rod conformation of CpG/SPG, enhanced the efficacy of a cancer vaccine. The present results indicate that CL-CpG can be used as a potent vaccine adjuvant for the treatment of cancers and infectious diseases.

Topics: Adjuvants, Immunologic; Animals; beta-Glucans; Cancer Vaccines; Cross-Linking Reagents; Cytokines; Drug Delivery Systems; Gels; Immunization; Mice; Neoplasms; Oligodeoxyribonucleotides; Ovalbumin; RAW 264.7 Cells; Toll-Like Receptor 9

Tumors can induce the generation and accumulation of immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs) in a tumor microenvironment, contributing to tumor escape from immunological attack. Although dendritic cell-based cancer vaccines can initiate antitumor immune responses, tumor-educated dendritic cells (TEDCs) involved in the tolerance induction have attracted much attention recently. In this study, we investigated the effect of β-glucan on TEDCs and found that β-glucan treatment could promote the maturation and migration of TEDCs and that the suppressive function of TEDCs was significantly decreased. Treatment with β-glucan drastically decreased the levels of regulatory T (Treg) cells but increased the infiltration of macrophages, granulocytes and DCs in tumor masses, thus elicited Th1 differentiation and cytotoxic T-lymphocyte responses and led to a delay in tumor progression. These findings reveal that β-glucan can inhibit the regulatory function of TEDCs, therefore revealing a novel function for β-glucan in immunotherapy and suggesting its potential clinical benefit. β-Glucan directly abrogated tumor-educated dendritic cells-associated immune suppression, promoted Th1 differentiation and cytotoxic T-lymphocyte priming and improved antitumor responses.

Topics: beta-Glucans; Cancer Vaccines; Cell Differentiation; Dendritic Cells; Humans; Immunity, Cellular; Immunotherapy; Macrophages; Myeloid Cells; Neoplasms; T-Lymphocytes, Cytotoxic; T-Lymphocytes, Regulatory; Tumor Microenvironment

Invasive pulmonary aspergillosis (IPA) is an important cause of morbidity/mortality in immunocompromised critically ill patients. New diagnostic strategies for early detection of IPA include the noninvasive biomarkers 1,3-β-d-glucan (BDG), serum, and bronchoalveolar (BAL) fluid galactomannan (GM). The aim of this study was to compare these markers for early detection of IPA in immunosuppressed critically ill patients.. Between December 2014 and December 2015, 49 immunosuppressed patients with respiratory failure were treated at our intensive care unit (ICU). We compared the BDG Fungitell assay with GM Platelia assay in serum and BAL for early detection of IPA. All tests were performed initially after admission at the ICU.. In our study with 49 patients, 13 (26%) had probable IPA. These patients had a higher Acute Physiology And Chronic Health Evaluation II score (28 vs 23, P<.001), Sequential Organ Failure Assessment score (16 vs 14, P<.001), more neutropenia (77% vs 30%, P<.001), worse Horowitz Index (99 vs 73 P<.020), a longer ICU stay (26 vs 17 days, P<.044), and a higher mortality rate (77% vs 58%, P<.001) as compared with patients without probable IPA. The used biomarker BDG presented in patients with probable IPA showed significantly higher levels as compared with patients without probable IPA (375 [103-1000 pg/mL; P<.001] vs 64 [30-105 pg/mL; P < .001]). Comparison of BDG with GM showed that positive serum GM could be detected in only 4 (30%), whereas positive BAL GM could be detected in 12 (92%; mean optical density index, 3.7) of 13 probable IPA cases. These results can be expressed as an overall sensitivity of 88% and a specificity of 82% for probable IPA using the BDG Fungitell assay, a sensitivity of 35% and a specificity of 70% using the serum GM Platelia assay, and a sensitivity of 70% and a specificity of 94% using the BAL GM Platelia assay. The negative predictive values of the used tests were 94% for the BDG Fungitell assay, 94% for the serum GM Platelia assay, and 90% for the BAL GM Platelia assay.. 1,3-β-d-Glucan may be a useful marker for patients under surveillance at risk for IPA. In critically ill patients with immunosuppression, early diagnosis of IPA may be improved by BDG as compared with serum GM. However, diagnostic performance and accuracy increase when BDG is run in parallel with GM from BAL; moreover, the association of the 2 parameters has also the advantage of detecting early and reliable IPA.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; APACHE; Aspergillus; Autoimmune Diseases; beta-Glucans; Biomarkers; Bronchoalveolar Lavage Fluid; Critical Illness; Early Diagnosis; Female; Galactose; Graft Rejection; Humans; Immunocompromised Host; Immunosuppressive Agents; Intensive Care Units; Invasive Pulmonary Aspergillosis; Length of Stay; Male; Mannans; Middle Aged; Mortality; Neoplasms; Neutropenia; Organ Dysfunction Scores; Organ Transplantation; Respiration, Artificial; Respiratory Insufficiency; Retrospective Studies; Sensitivity and Specificity; Young Adult

Dectin-1 signalling in dendritic cells (DCs) has an important role in triggering protective antifungal Th17 responses. However, whether dectin-1 directs DCs to prime antitumour Th9 cells remains unclear. Here, we show that DCs activated by dectin-1 agonists potently promote naive CD4(+) T cells to differentiate into Th9 cells. Abrogation of dectin-1 in DCs completely abolishes their Th9-polarizing capability in response to dectin-1 agonist curdlan. Notably, dectin-1 stimulation of DCs upregulates TNFSF15 and OX40L, which are essential for dectin-1-activated DC-induced Th9 cell priming. Mechanistically, dectin-1 activates Syk, Raf1 and NF-κB signalling pathways, resulting in increased p50 and RelB nuclear translocation and TNFSF15 and OX40L expression. Furthermore, immunization of tumour-bearing mice with dectin-1-activated DCs induces potent antitumour response that depends on Th9 cells and IL-9 induced by dectin-1-activated DCs in vivo. Our results identify dectin-1-activated DCs as a powerful inducer of Th9 cells and antitumour immunity and may have important clinical implications.

Topics: Animals; beta-Glucans; Cell Differentiation; Chemokines; Cross-Priming; Dendritic Cells; Humans; Immunity; Lectins, C-Type; Mice, Inbred C57BL; Neoplasms; NF-kappa B; OX40 Ligand; Proto-Oncogene Proteins c-raf; Signal Transduction; Syk Kinase; T-Lymphocytes, Helper-Inducer; Tumor Necrosis Factor Ligand Superfamily Member 15

In this study, a new non-toxic, biodegradable, biocompatible and water-soluble carboxylic curdlan bearing the dissociable COOH group in 100% purity, which was prepared by 4-acetamido-TEMPO-mediated oxidation, was hydrophobically modified by deoxycholic acid (DOCA) to attain novel amphiphilic curdlan derivatives (CCDs) for the preparation of nano-carriers for antitumor drug doxorubicin (DOX). Under the effect of ultrasonication, the carboxylic curdlan derivatives in water were self-aggregated into spherical nanoparticles with diameters ranging from 214 nm to 380 nm. The critical aggregation concentrations decreased from 0.047 mg/mL to 0.016 mg/mL with increasing DS of DOCA. DOX-loaded CCD nanoparticles were prepared in an aqueous medium with dialysis method. The DOX-CCD nanoparticles exhibited pH- and dose-dependent drug release profiles during in vitro release experiments. Moreover, the drug transport mechanism was Fickian diffusion according to the Ritger-Peppas model. The CCD nanoparticles might be explored as potential carriers for hydrophobic drugs with controlled release and delivery functions.

Topics: Antineoplastic Agents; beta-Glucans; Cell Line, Tumor; Chitosan; Deoxycholic Acid; Doxorubicin; Drug Carriers; Humans; Hydrophobic and Hydrophilic Interactions; Nanoparticles; Neoplasms

A water soluble β-1,3-glucan schizophyllan (SPG) can be recognized by an immunocyte receptor called dectin-1. When we introduced naphthalene into the side chain of SPG (nSPG), it formed nanogel by physical cross-link and gained capability to ingest hydrophobic compounds such as doxorubicin. Our in vitro assay revealed that this nanogel can be used as specific delivery of anti-cancer drugs to immunocytes.

Topics: Antigen-Presenting Cells; Antineoplastic Agents; beta-Glucans; Doxorubicin; Drug Delivery Systems; Humans; Hydrophobic and Hydrophilic Interactions; Models, Biological; Molecular Structure; Nanogels; Naphthalenes; Neoplasms; Polyethylene Glycols; Polyethyleneimine

Topics: Agaricales; Antineoplastic Agents, Phytogenic; beta-Glucans; Humans; Neoplasms; Plant Extracts

β-glucans have been reported to function as a potent adjuvant to stimulate innate and adaptive immune responses. However, β-glucans from different sources are differential in their structure, conformation, and thus biologic activity. Different preparations of β-glucans, soluble versus particulate, further complicate their mechanism of action. Here we show that yeast-derived particulate β-glucan activated dendritic cells (DCs) and macrophages via a C-type lectin receptor dectin-1 pathway. Activated DCs by particulate β-glucan promoted Th1 and cytotoxic T-lymphocyte priming and differentiation in vitro. Treatment of orally administered yeast-derived particulate β-glucan elicited potent antitumor immune responses and drastically down-regulated immunosuppressive cells, leading to the delayed tumor progression. Deficiency of the dectin-1 receptor completely abrogated particulate β-glucan-mediated antitumor effects. In contrast, yeast-derived soluble β-glucan bound to DCs and macrophages independent of the dectin-1 receptor and did not activate DCs. Soluble β-glucan alone had no therapeutic effect but significantly augmented antitumor monoclonal antibody-mediated therapeutic efficacy via a complement activation pathway but independent of dectin-1 receptor. These findings reveal the importance of different preparations of β-glucans in the adjuvant therapy and allow for the rational design of immunotherapeutic protocols usable in clinical trials.

Topics: Adaptive Immunity; Adjuvants, Immunologic; Animals; beta-Glucans; Cell Line, Tumor; Cells, Cultured; Dendritic Cells; Humans; Immunity, Innate; Lectins, C-Type; Macrophages; Membrane Proteins; Mice; Mice, Inbred C57BL; Neoplasms; Nerve Tissue Proteins; Phagocytosis; Saccharomyces cerevisiae; T-Lymphocytes, Cytotoxic; Th1 Cells

Photodynamic therapy (PDT) combines a drug or photosensitizer with a specific type of light to kill cancer cells. The cellular damage induced by PDT leads to activation of the DNA damage repair, which is an important factor for modulating tumor sensitivity to this treatment. beta-Glucans are natural polysaccharides that bind complement receptor 3 on the effector cells, thereby activating them to kill tumor cells during PDT. The hypothesis of the present study was that adjuvant therapy with beta-glucans would increase the efficacy of PDT. C57BL/6 female mice were subcutaneously implanted with Lewis lung carcinoma cells. Ten days after implantation, the mice were administered intravenously sodium porfimer (10 mg/kg) 24 h prior to laser irradiation, with or without oral administration of beta-glucan (400 microg/d/mouse, 5 days) from either barley, baker's yeast, or marine brown algae that contains the storage glucan, laminarin. Tumor volume and necrotic area in excised tumors were measured. The expression of proliferating cell nuclear antigen (PCNA) was determined as an indicator of the activity of the DNA damage repair system. PDT in combination with each beta-glucan significantly reduced tumor growth (P < 0.05, n = 10) and expression of PCNA (P < 0.001, n = 9), and increased necrosis in tumor tissues (P < 0.001, n = 9). Furthermore, each structurally different

Topics: Animals; beta-Glucans; Combined Modality Therapy; Female; Lasers; Mice; Mice, Inbred C57BL; Neoplasms; Photochemotherapy; Xenograft Model Antitumor Assays

The purpose of this study was to develop nanoparticles made of cholesterol-conjugated carboxymethyl curdlan (CCMC) entrapping epirubicin (EPB) and establish their in vitro and in vivo potential. CCMC was synthesized and characterized by Fourier transform infrared spectra (FT-IR) and proton nuclear magnetic resonance spectra ((1)H NMR). The degrees of substitution (DS) of the cholesterol moiety were 2.3, 3.5 and 6.4, respectively. EPB-loaded CCMC-3.5 nanoparticles were prepared by the remote loading method. The physicochemical characteristics, drug loading efficiency and drug release kinetics of EPB-loaded CCMC-3.5 nanoparticles were characterized. The in vitro release profiles revealed that EPB release was sensitive to the pH as well as the drug loading contents. The cellular cytotoxicity and cellular uptake were accessed by using human cervical carcinoma (HeLa) cells. The EPB-loaded CCMC-3.5 nanoparticles were found to be more cytotoxic and have a broader distribution within the cells than the free EPB. The in vivo pharmacokinetics and biodistribution were investigated after intravenous injection in rats. Promisingly, a 4.0-fold increase in the mean residence time (MRT), a 4.31-fold increase in the half-life time and a 6.69-fold increase in the area under the curve (AUC 0-->infinity) of EPB were achieved for the EPB-loaded CCMC-3.5 self-assembled nanoparticles compared with the free EPB. The drug level was significantly increased in liver at 24 and 72 h; however, it decreased in heart at 8 and 24 h compared with the free EPB. The in vivo anti-tumor study indicated that the EPB-loaded CCMC-3.5 self-assembled nanoparticles showed greater anti-tumor efficacy than the free EPB. Taken together, the novel CCMC self-assembled nanoparticles might have potential application as anti-cancer drug carriers in a drug delivery system due to good results in vitro and in vivo.

Topics: Animals; beta-Glucans; Cell Death; Cell Proliferation; Cell Survival; Cholesterol; Drug Carriers; Epirubicin; HeLa Cells; Humans; Injections, Intravenous; Male; Mice; Microscopy, Confocal; Nanoparticles; Neoplasms; Particle Size; Rats; Rats, Wistar; Spectrophotometry, Infrared; Tissue Distribution

The beneficial properties of β-glucans have been recognized for centuries. Their proposed mechanisms of action in cancer therapy occur via stimulation of macrophages and priming of innate neutrophil complement receptor 3 for eliciting complement receptor 3-dependent cellular cytotoxicity of iC3b-opsonized tumor cells. The current study is to investigate whether β-glucan therapy has any effect on antitumor adaptive T-cell responses.. We first examined the trafficking of orally administered particulate yeast-derived β-glucan and its interaction with dendritic cells (DC) that captured tumor materials. Antigen-specific T cells were adoptively transferred into recipient mice to determine whether oral β-glucan therapy induces augmented T-cell responses. Lewis lung carcinoma and RAM-S lymphoma models were used to test oral β-glucan therapeutic effect. Further mechanistic studies including tumor-infiltrating T cells and cytokine profiles within the tumor milieu were determined.. Orally administered particulate β-glucan trafficked into spleen and lymph nodes and activated DCs that captured dying tumor cells in vivo, leading to the expansion and activation of antigen-specific CD4 and CD8 T cells. In addition, IFN-γ production of tumor-infiltrating T cells and CTL responses were significantly enhanced on β-glucan treatment, which ultimately resulted in significantly reduced tumor burden. Moreover, β-glucan-treated tumors had significantly more DC infiltration with the activated phenotype and significant levels of Th1-biased cytokines within the tumor microenvironment.. These data highlight the ability of yeast-derived β-glucan to bridge innate and adaptive antitumor immunity and suggest that it can be used as an adjuvant for tumor immunotherapy.

Topics: Adjuvants, Immunologic; Administration, Oral; Animals; beta-Glucans; Carcinoma, Lewis Lung; Cells, Cultured; Dendritic Cells; Dosage Forms; Drug Evaluation, Preclinical; Immunity, Cellular; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neoplasms; Phagocytosis; Powders; T-Lymphocytes

Invasive fungal infections (IFIs) remain a major cause of infectious morality in neutropenic patients receiving chemotherapy or hematopoietic stem cell transplantation (HSCT). Micafungin exhibits broad antifungal activity against both Aspergillus and Candida species. We performed a retrospective study to determine the efficacy and safety of prophylactic micafungin against IFI in pediatric neutropenic patients during chemotherapy or HSCT.. Forty patients were given micafungin (3 mg/kg/day) intravenously for neutropenia: 131 patient-cycles (39 patients) after chemotherapy and 15 patient-cycles (14 patients) after HSCT. Median duration of neutropenia and micafungin prophylaxis was 13 and 23 days after chemotherapy and HSCT, respectively.. Treatment success rate, defined as absence of proven, probable, possible, or suspected IFIs, was 93.9% (121/131) and 80.0% (12/15) for chemotherapy and HSCT, respectively. Proven or probable IFI was documented in only one patient after HSCT. No adverse events were observed that could be related to micafungin prophylaxis.. These results suggest that prophylactic micafungin is well tolerated and may prevent IFIs in pediatric patients with neutropenia receiving chemotherapy or HSCT.

Topics: Adolescent; Antifungal Agents; Antineoplastic Agents; beta-Glucans; Child; Child, Preschool; Echinocandins; Hematopoietic Stem Cell Transplantation; Humans; Infant; Lipopeptides; Micafungin; Mycoses; Neoplasms; Neutropenia; Retrospective Studies

We recently elucidated the structure of a highly branched 1,3-beta-D-glucan with 6-monoglucopyranosyl side chains, extracted from Aureobasidium pullulans (AP-FBG). Although the biological effects of beta-D-glucans are known to depend on their structures, the effects of a highly branched 1,3-beta-D-glucan on the production of cytokines by leukocytes in mice have not yet been elucidated. In this study, we found that AP-FBG strongly induced the production of various cytokines, especially Th1 cytokines (e.g., IFN-gamma and IL-12p70) and Th17 cytokines (e.g., IL-17A), but did not induce the production of IL-4, IL-10, and TNF-alpha in DBA/2 mouse-derived splenocytes in vitro.

Topics: Animals; beta-Glucans; Cells, Cultured; Cytokines; Fungi; Immunization; Infections; Male; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Neoplasms; Spleen; Th1 Cells

Topics: Antineoplastic Agents, Phytogenic; beta-Glucans; Complementary Therapies; Grifola; Humans; Neoplasms; Phytotherapy; Plant Extracts

Invasive fungal infection (IFI) is a leading cause of infection-related mortality among patients with cancer and prolonged neutropenia and among allogeneic hematopoietic stem cell transplant recipients with graft-versus-host disease. Invasive candidiasis was the principal IFI in the period predating fluconazole prophylaxis, whereas today, invasive aspergillosis and other mold infections cause the majority of deaths from fungal infection in this patient population. The changing epidemiology of IFI, in addition to advances made in antifungal therapeutics and early diagnosis of IFI, warrant a reevaluation of earlier strategies aimed at prevention and early treatment of IFI that were developed several years ago. Here, we propose that persistent neutropenic fever is nonspecific for an IFI and should not be used as the sole criterion for empirical modification in the antifungal regimen in a patient receiving mold-active prophylaxis. We explore the potential benefits and gaps in knowledge associated with employing chest CT scans and laboratory markers as diagnostic adjuncts for IFI. Finally, we discuss the implications of newer antifungal agents and diagnostic adjuncts in the design of future clinical trials to evaluate prophylaxis and early prevention strategies.

Topics: Antifungal Agents; beta-Glucans; Biomarkers; Evaluation Studies as Topic; Fever; Fungi; Galactose; Hematopoietic Stem Cell Transplantation; Humans; Mannans; Mycoses; Neoplasms; Neutropenia; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Tomography, X-Ray Computed; Yeasts

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.

Topics: Adjuvants, Immunologic; Animals; Antibodies, Monoclonal; beta-Glucans; Complement C3; Glucans; Lymphoid Tissue; Macrophage-1 Antigen; Macrophages; Mice; Neoplasms

The postulated anticancer effect of D-fraction, the bioactive extract of maitake mushroom, on three types (CF33, CF21, and CL-1) of canine cancer cells was evaluated. The effect of D-fraction on several human cancer cells was also investigated. The effect of other beta-glucan products was likewise examined. D-fraction was highly effective on the canine cancer cells, either potently inhibiting cell growth or directly killing cells. Similar effects were also demonstrated in certain human cancer cells. However, other beta-glucan products relevant to D-fraction had no such effects on canine cancer cells. Therefore, D-fraction is a potent natural agent that could be useful in treating canine cancers as well as other veterinary cancers.

Topics: Animals; Antineoplastic Agents; beta-Glucans; Cell Division; Cell Survival; Dog Diseases; Dogs; Grifola; Humans; Killer Cells, Natural; Neoplasms; Tumor Cells, Cultured

ICR mice were treated with a carcinogen, N-butyl-N'-butanolnitrosoamine BBN), every day for 8 consecutive weeks and the effects of oral administration of edible mushrooms on the induction of urinary bladder carcinoma and on the activities of macrophages and lymphocytes were studied. Bladder carcinoma were found in all 10 mice (100%) treated with BBN alone, while we observed carcinoma only in 9 of 17 mice (52.9%), in 7 of 15 mice (46.7%) and 13 of 20 mice (65.0%) treated with Lentinus edodes, Grifola frondosa and Pleurotus ostreatus, respectively. Chemotactic activity of macrophages was suppressed in mice treated with BBN alone but maintained almost the normal level in mice treated with BBN plus Lentinus, Grifola or Pleurotus. Lymphocytes collected from mice treated with BBN plus each mushroom showed almost normal blastogenic response against concanavalin A, although those from mice treated with BBN alone completely retarded their response. Cytotoxic activity of lymphocytes against Yac-1 cells was also maintained at a normal level in mice treated with BBN plus each mushroom. Whereas in mice treated with BBN alone significant depression of NK cell activity occurred. Significantly higher cytotoxic activity against P-815 cells was observed in lymphocytes from mice treated with BBN plus each mushroom than that in lymphocytes from normal mice or mice treated with BBN alone.

Topics: Animals; Antibiotics, Antineoplastic; Basidiomycota; beta-Glucans; Butylhydroxybutylnitrosamine; Carcinogens; Cells, Cultured; Chemotaxis; Concanavalin A; Cytotoxicity, Immunologic; Disease Outbreaks; Eating; Female; Glucans; Lentinan; Lymphocyte Activation; Lymphocytes; Macrophages; Medicine, Traditional; Mice; Mice, Inbred ICR; Neoplasms; Polyporaceae; Polysaccharides; Spleen; Urinary Bladder Neoplasms