epiglucan and Colorectal-Neoplasms

β-Glucan, an essential natural polysaccharide widely distributed in cereals and microorganisms, exhibits extensive biological activities, including immunoregulation, anti-inflammatory, antioxidant, antitumor properties, and flora regulation. Recently, increasing evidence has shown that β-glucan has activities that may be useful for treating intestinal diseases, such as inflammatory bowel disease (IBD), and colorectal cancer. The advantages of β-glucan, which include its multiple roles, safety, abundant sources, good encapsulation capacity, economic development costs, and clinical evidence, indicate that β-glucan is a promising polysaccharide that could be developed as a health product or medicine for the treatment of intestinal disease. Unfortunately, few reports have summarized the progress of studies investigating natural β-glucan in intestinal diseases. This review comprehensively summarizes the structure-activity relationship of β-glucan, its pharmacological mechanism in IBD and colorectal cancer, its absorption and transportation mechanisms, and its application in food, medicine, and drug delivery, which will be beneficial to further understand the role of β-glucan in intestinal diseases.

Topics: Anti-Inflammatory Agents; Antioxidants; beta-Glucans; Colorectal Neoplasms; Dietary Carbohydrates; Humans; Inflammatory Bowel Diseases; Polysaccharides

The previous reports have established a strong link between diet, lifestyle, and gut microbiota population with the onset of the colorectal cancer (CRC). Administration of probiotics has become a particular interest in prevention and treatment of CRC. As potential dietary complements, probiotics might be able to lower the risk of CRC and manage the safety of traditional cancer therapies such as surgery, radiation therapy, and chemotherapy. This review investigates the promising effects of probiotics as biotherapeutics, with due attention to possible clinical application of yeast probiotics in prevention and treatment of CRC. In addition, various underlying anti-cancer mechanisms are covered here based on scientific evidence and findings from numerous experimental studies. Application of probiotics as biotherapeutics in CRC, however, needs to be approved by human clinical trials. It is of prime concern, to find potential probiotic strains, effective doses for administrations and regimes, and molecular mechanisms involved in prevention and treatment.

Topics: Antineoplastic Agents; beta-Glucans; Clinical Trials as Topic; Colorectal Neoplasms; Databases, Factual; Disease Progression; Folic Acid; Gastrointestinal Microbiome; Humans; Inflammation; MAP Kinase Signaling System; Probiotics; Saccharomyces boulardii; Saccharomyces cerevisiae; Signal Transduction; Yeasts

Imprime PGG (β(1,6)-[poly-(1,3)-D-glucopyranosyl]-poly-β(1,3)-D-glucopyranose) is an innate immune cell modulator that primes neutrophils and monocytes/macrophages to exert antitumor activity against complement opsonized tumor cells. In patients with KRAS-mutant colorectal cancer (CRC), cetuximab alone is ineffective; however, it can bind to tumor cells and induce opsonization for recognition by Imprime PGG-bound innate immune cells. The primary objective of this study was to determine the antitumor activity of Imprime PGG in combination with cetuximab in patients with KRAS-mutant metastatic CRC.. The study had a 2-stage Simon optimal design with 80% power to detect a target objective response rate (ORR) of ≥10% at a 10% significance level. Patients received weekly Imprime PGG (4 mg/kg) and cetuximab (loading dose, 400 mg/m(2), then 250 mg/m(2)) intravenously. The primary end point was ORR; secondary end points included duration of response (DOR), time to progression (TTP), overall survival (OS), disease control rate, progression-free survival, and safety. Stage 1 of the study was to enroll 17 evaluable patients.. One partial response (5.6%) was observed among 18 patients enrolled into stage 1. Median DOR was 4.2 months, TTP 2.7 months, and OS 6.6 months. Overall, observed toxicity was as expected from cetuximab alone. The most common (≥20%) adverse events related to Imprime PGG were fatigue (7 patients; 38.9%), infusion reaction (4 patients; 22.2%), and headache (4 patients; 22.2%). There was no Grade 4 toxicity nor treatment-related deaths.. Imprime PGG in combination with cetuximab treatment in patients with KRAS-mutant CRC showed compelling, albeit modest, clinical activity. This study provides proof of principle that Imprime PGG, in combination with complement-activating antibodies, is associated with clinical activity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Colorectal Neoplasms; Disease-Free Survival; Female; Glucans; Humans; Immunotherapy; Kaplan-Meier Estimate; Male; Middle Aged; Mutation; Neoplasm Staging; Proto-Oncogene Proteins p21(ras); Treatment Outcome

The present study aims to evaluate the antioxidant effect of beta-glucan on oxidative DNA damage by comet assay.. A total of 19 adult females and males diagnosed with stage 3-4 colorectal cancer and a control group of 20 age-matched healthy subjects were enrolled in the study. Blood samples of the participants were analyzed using Comet Assay for the parameters of DNA damage.. Significantly increased DNA damage was observed in patients versus the control group as indicated by greater values of tail moment, tail percent DNA and tail length. Following incubation with β-glucan, a substantial reduction was found in the aforementioned parameters of DNA damage. Comet assay revealed significant levels of endogenous DNA damage in patients as shown by remarkable increases in the tail moment, the percentage of DNA in the tail and the tail length values, in comparison with the control group. Following treatment of fresh whole blood with β-glucan incubation, DNA damages were significantly reduced, but lower values were observed after β-glucan incubation in the patient group versus control group.. β-Glucan was found to reduce DNA damage substantially in colorectal cancer patients and show antimutagenic effects. Our results suggested that dietary β-glucan intake might be important in the genesis of colorectal cancer tumors.

Topics: Adult; Antioxidants; beta-Glucans; Colorectal Neoplasms; Comet Assay; DNA; DNA Damage; Female; Humans; Male; Oxidative Stress

BTH1677 is a beta-glucan pathogen-associated molecular pattern (PAMP) being evaluated as a novel immunotherapy of cancer. We previously described that the presence of antibodies against beta-glucan (ABA) in serum is necessary for BTH1677 antitumoral activity. We hypothesized that infusion of immunoglobulin can reinstate responses to BTH1677 in individuals with low ABA levels.. We report two single-patient studies: one in a patient with metastatic colorectal cancer who received BTH1677, combined with tumor targeting antibody cetuximab; and a second in a patient with metastatic neuroendocrine tumor who received BTH1677 combined with immune checkpoint inhibitor pembrolizumab.. The patients had low serum titers of ABA and low innate immune effector functionality induced by BTH1677. Addition of intravenous immunoglobulins restored innate immune activity of BTH1677 and induced clinically meaningful anti-tumoral activity, with long-term disease control.. Infusion of immunoglobulin can restore activity of BTH1677 in individuals with low serum ABA level.

Topics: Aged, 80 and over; Antibodies; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; beta-Glucans; Cetuximab; Colorectal Neoplasms; Female; Glucans; Humans; Immunoglobulins; Immunotherapy; Middle Aged; Neuroendocrine Tumors

An 86-year-old woman with Borrmann type III colorectal cancer (Union for International Cancer Control pT4aN2bM1c, pStage IVc) had received dexamethasone for the last 6 months as palliative care. She presented with a low-grade fever, chest pain and cough. Chest radiography on admission showed cavities and consolidations bilaterally in the upper lobes. A blood examination on admission revealed highly elevated serum β-d-glucan levels. The diagnosis by bronchoscopy was pulmonary nocardiosis. With trimethoprim/sulfamethoxazole and imipenem/cilastatin, the β-d-glucan levels were decreased, and chest X-ray showed improvement after 1 month. β-d-glucan is known to be a biomarker of fungal infection. It is possible that β-d-glucan levels also indicate a pulmonary infection by

Topics: Aged, 80 and over; Anti-Bacterial Agents; Antineoplastic Agents; beta-Glucans; Cilastatin, Imipenem Drug Combination; Colorectal Neoplasms; Dexamethasone; Female; Humans; Nocardia Infections; Proteoglycans; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Colorectal cancer (CRC) is the third most common tumor worldwide, and recent epidemiological studies have indicated that obesity contributes to the morbidity and mortality of CRC. Furthermore, obesity-related adipokines have been shown to be closely related to the incidence of CRC, but the underlying mechanisms are unclear. Here, we investigated the effects of high-fat diet-induced adipokines and cytokines on the development of CRC in vitro and in vivo. For the in vivo assays, we divided 2-week-old C57BL/6J-ApcMin/J male mice into three groups: normal-fat diet (ND), high-fat and high-sugar feed (HFHS), and high-fat and low-sugar feed (HFLS). After 1 week, all mice were injected with 20 mg·kg

Topics: Adipokines; Animals; beta-Glucans; Cell Line, Tumor; Cell Movement; Cell Proliferation; Colorectal Neoplasms; Cytokines; Diet, High-Fat; Dimethylhydrazines; Disease Progression; Male; Mice; Neoplasm Invasiveness; Obesity

The World Health Organization (WHO) reported that colorectal cancer (CRC) was the third most common cancer in men and the second in women, worldwide. Our previous meta-analysis found Sophora flavescens increased tumour response rate in randomised controlled trials of CRC. We hypothesised that its principal constituent matrine had exerted anti-tumour effects.. To elucidate its mechanisms of action we investigated the dose-related anti-tumour effects of matrine on four human CRC cell-lines: LS174T, Caco-2, SW1116 and RKO. In a LS174T xenografted tumour model in nude mice we assessed the effects of matrine and oxaliplatin on tumour volume, weight and morphology. Computer simulated dockings for target proteins were also conducted.. Cell viability, cell cycle and apoptosis were measured by Cell Counting Kit-8 and flow cytometry, and Annexin V-FITC/PI double staining assay respectively. Western blot was performed to examine the expression of Bax, Bcl-2 and caspase-3 in the cells. The xenograft model and immunohistochemistry were used to investigate the effect of matrine in vivo. Oxaliplatin was set as positive control. Molecular docking was performed to predict the binding modes of matrine and oxaliplatin with target proteins using CDOCKER algorithm.. Matrine inhibited proliferation of cancer cells in a dose- and time-dependent manner. Matrine induced cell-cycle arrest at G1/G0 phase, induced apoptosis and reduced expression of Bcl-2 and caspase-3 while up-regulating Bax and cleaved caspase-3 in the four CRC cells. In vivo, matrine significantly inhibited tumour growth without side effects on physical health compared to the negative (vehicle) control group. Mice in the oxaliplatin group lost vigour, became frail and lost weight. Expression of Bcl-2 in tumour tissue was lower and Bax expression was higher in the matrine-treated groups compared to the negative control. In computer-simulated docking, matrine successfully docked into active sites of Bcl-2 and caspase-3.. Matrine inhibited growth of colorectal cancer cells in vitro and in vivo. A molecular mechanism was apoptosis induction via effects on Bcl-2, Bax and caspase-3. Moreover, matrine showed minimum side effects and may provide a candidate for the development of new therapies for colorectal cancer.

Topics: Alkaloids; Animals; Apoptosis; bcl-2-Associated X Protein; beta-Glucans; Caco-2 Cells; Caspase 3; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; Humans; Male; Matrines; Mice; Mice, Nude; Molecular Docking Simulation; Proto-Oncogene Proteins c-bcl-2; Quinolizines; Sophora; Xenograft Model Antitumor Assays

The present study aimed to determine the effect of oral β-glucan on mucositis and leukopenia in 62 consecutive patients with colorectal cancer treated with an adjuvant FOLFOX-4 regimen. The patients were retrospectively evaluated in 2 groups: one group received β-glucan and the other did not (control group). Leucocytes, neutrophils, and platelets were evaluated before and 1 week after chemotherapy and oral mucositis and diarrhea were noted. Leucocyte and neutrophil counts after chemotherapy in the β-glucan group were 7,300/mm3 and 3,800/mm3, respectively, and the reductions, as compared to baseline, were not significant (p=0.673 and 0.784). The median platelet count was 264,000/mm3 after chemotherapy in the β-glucan group and the reduction, as compared to baseline, was borderline significant (p=0.048). In the control group, reduction in leucocyte, neutrophil, and platelet counts was statistically significant. Oral mucositis and diarrhea were less common in the β-glucan group. We conclude that β-glucan can be used to reduce the adverse effects of chemotherapy.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; beta-Glucans; Chemotherapy, Adjuvant; Cohort Studies; Colorectal Neoplasms; Diarrhea; Female; Fluorouracil; Humans; Leucovorin; Leukocyte Count; Leukopenia; Male; Middle Aged; Mucositis; Organoplatinum Compounds; Platelet Count; Retrospective Studies; Stomatitis; Treatment Outcome

Cisplatin is broadly used clinically as an anticancer drug. Despite its significant anticancer activity, cisplatin-induced nephrotoxicity and myelosuppression limit its use. MD-Fraction is glucan purified from maitake (Grifola frondosa), which has beta-1, 6-main chain with beta-1, 3-branches, has been reported to exhibit antitumor and antimetastatic activities by enhancing the immune system. In this study, we demonstrate that MD-Fraction in combination with cisplatin significantly enhanced antitumor and antimetastatic activity compared to cisplatin alone. MD-Fraction reduced decreases in body weight, spleen weight and the number of immunocompetent cells such as macrophages, DCs and NK cells in cisplatin-treated mice. MD-Fraction also induced IL-12p70 production by splenocytes, resulting in increased NK cell activity in cisplatin-treated mice. MD-Fraction significantly increased the mRNA expression of GM-CSF, G-CSF, M-CSF, IFN-gamma, IL-12 p40 in splenocytes and reduced the decrease in the number of CFU-GM colonies in cisplatin-treated bone marrow. These facts suggest that MD-Fraction can reduce cisplatin-induced myelosuppression. Moreover, treatment with MD-Fraction significantly reduced cisplatin-induced nephrotoxicity accompanied by increases in serum creatinine level, necrosis and apoptosis of renal tubular cells. These results suggest that MD-Fraction in combination with cisplatin cannot only enhance antitumor and antimentastatic acitivity, but also reduce cisplatin-induced myelotoxicity and nephrotoxicity.

Topics: Animals; Antigens, Fungal; Antineoplastic Agents; Apoptosis; beta-Glucans; Bone Marrow; Cell Line, Tumor; Cisplatin; Colony-Forming Units Assay; Colorectal Neoplasms; Creatinine; Drug Synergism; Female; Grifola; Interferon-gamma; Interleukin-12; Kidney; Killer Cells, Natural; Lung Neoplasms; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Organ Size; Phytotherapy

Complement (C) regulatory proteins decrease the effectiveness of immunotherapeutic anti-cancer antibodies. Bispecific mAb (bi-mAb) that target a tumor antigen and simultaneously inhibit a C regulator increase the effectiveness of such a therapy. Here we investigated the mechanism by which bi-mAb increase tumor cell lysis. Apart from C-dependent cytotoxicity, C activation can lead to complement receptor 3 (CR3)-dependent cellular cytotoxicity (CR3-DCC) by CR3-positive effector cells in the presence of beta-glucan. Here we show that an anti-Ep-CAM*anti-CD55 bi-mAb induced more than threefold higher CR3-DCC (71%) of human colorectal cancer cells compared with anti-Ep-CAM alone (20%). This CR3-DCC was dependent on the binding of the anti-CD55 arm of tumor-bound anti-Ep-CAM*anti-CD55 bi-mAb to effector cell CD55, CR3 priming by beta-glucan and the presence of iC3b on the target cell. Comparable lysis could be obtained in the absence of iC3b, when CR3 and CD55 were cross-linked on the effector cells, suggesting cooperation between CD55 and CR3 in signal transduction. Tumor cells with low antigen expression were effectively lysed via this mechanism in contrast to direct C-dependent cytotoxicity. These data imply that the effectiveness of mAb immunotherapy can be improved using anti-tumor antigen*anti-CD55 bi-mAb and beta-glucan, thereby initiating CR3-DCC as an additional effector mechanism that is efficient for eradication of tumor cells with lower antigen expression.

Topics: Antibodies, Bispecific; Antigens, Neoplasm; beta-Glucans; CD55 Antigens; Cell Adhesion Molecules; Cell Communication; Cell Line, Tumor; Colorectal Neoplasms; Cross-Linking Reagents; Cytotoxicity, Immunologic; Epithelial Cell Adhesion Molecule; Flow Cytometry; Humans; Macrophage-1 Antigen