epiglucan and Breast-Neoplasms

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

To reduce the seroma formation following mastectomy and axillary dissection, many different techniques and drugs have been investigated. The aim of this study is to evaluate the effects of oral β-glucan on drain fluid and efficacy of daily drainage and drain removal day in mastectomy patients.. One hundred and thirty breast cancer patients of Ankara Oncology Training and Research Hospital were divided into 2 groups by consecutive randomization (n = 65 each). β-glucan 10 mg capsules were administered to Group 1 twice a day for 10 days. Group 2 took placebos in the same manner. Age, menarche age, menopause, parity, history of oral contraceptives, comorbidities, postoperative daily drainage volumes and drain removal days were recorded and compared. Seroma samples during the first and second day of drainage were taken for analysis of Interleukin-6 (IL-6) and Tumor Necrosis Factor (TNF-α).. There was no difference between groups in terms of age, menarche age, menopause period, parity, oral contraceptive use and comorbidities. Group 1 showed significantly lower daily drainage volumes between days 2 and 8. Mean drain removal day was 7.16 ± 1.72 in Group 1 and 8.59 ± 2.27 in Group 2. The difference was significant (p < 0.001). TNF-α and IL-6 levels on days 1 and 2 in Group 1 were significantly lower (p < 0.001). In addition, β-glucan significantly shortened the number of days required for the drain removal in patients who have comorbidities (p = 0.018). The earliest removal was in patients without comorbidity and who received β-glucan (p = 0.002).. β-glucan decreased drain discharges after mastectomy. The drains were removed earlier in β-glucan administered patients.

Topics: Administration, Oral; Adult; beta-Glucans; Breast Neoplasms; Carcinoma; Double-Blind Method; Drainage; Female; Humans; Interleukin-6; Logistic Models; Mastectomy, Modified Radical; Middle Aged; Seroma; Treatment Outcome; Tumor Necrosis Factor-alpha; Wound Healing

Breast cancer is the most common female malignancy in the world. Beta glucan can be a hematopoietic and an immune modulator agent in cancer patients. The aim of this trial was to determine the effect of beta glucan on white blood cell counts and serum levels of IL-4 and IL-12 in women with breast cancer undergoing chemotherapy.. This randomized double-blind placebo-controlled clinical trial was conducted on 30 women with breast carcinoma aged 28-65 years. The eligible participants were randomly assigned to intervention (n=15) or placebo (n=15) groups using a block randomization procedure with matching based on age, course of chemotherapy and menopause status. Patients in the intervention group received two 10-mg capsules of soluble 1-3, 1-6, D-beta glucan daily and the control group receiving placebo during 21 days, the interval between two courses of chemotherapy. White blood cells, neuthrophil, lymphocyte and monocyte counts as well as serum levels of IL-4 and IL-12 were measured at baseline and at the end of the study as primary outcomes of the study.. In both groups white blood cell counts decreased after 21 days of the intervention, however in the beta glucan group, WBC was less decreased non significantly than the placebo group. At the end of the study, the change in the serum level of IL-4 in the beta glucan group in comparison with the placebo group was statistically significant (p=0.001). The serum level of IL-12 in the beta glucan group statistically increased (p=0.03) and comparison between two groups at the end of the study was significant after adjusting for baseline values and covariates (p=0.007).. The findings suggest that beta glucan can be useful as a complementary or adjuvant therapy and immunomodulary agent in breast cancer patients in combination with cancer therapies, but further studies are needed for confirmation.

Topics: Adult; Aged; Antineoplastic Agents; beta-Glucans; Body Weight; Breast Neoplasms; Dietary Supplements; Double-Blind Method; Eating; Female; Humans; Interleukin-12; Interleukin-4; Lymphocyte Count; Middle Aged; Monocytes; Neutrophils; Placebos

Glucans are glucose polymers that constitute a structural part of fungal cell wall. They can stimulate the innate immunity by activation of monocytes/macrophages. In human studies it has been shown that beta glucan has an immunomodulatory effect and can increase the efficacy of the biological therapies in cancer patients. In this prospective clinical trial we assessed in vivo effects of short term oral beta glucan administration on peripheral blood monocytes and their expression of activation markers in patients with advanced breast cancer.. 23 female patients with advanced breast cancer were included in the study. Median age of the patients was 52 years. Sixteen healthy females with a median age of 48 years served as the control group for comparing the initial blood samples. Peripheral blood samples were drawn on day zero and patients started receiving oral 1-3, 1-6, D-beta glucan daily. Blood samples were recollected on the 15th day. In the initial samples mean lymphocyte count was significantly lower in the patients with breast cancer (1281+/-306/mm(3) versus 1930+/-573/mm(3), p=0.04). In the patients with breast cancer, mean monocyte count which was 326+124/mm(3) at the beginning, was increased to 496+194/mm(3) at the 15th day (p=0.015). Expression of CD95 (Apo1/Fas) on CD14 positive monocytes was 48.17% at the beginning, which was increased to 69.23 % at the 15th day (p=0.002). Expression of CD45RA on CD14 positive monocytes was 49.9% at the beginning; it was increased significantly to 61.52% on day 15 (p=0.001).. Oral beta glucan administration seems to stimulate proliferation and activation of peripheral blood monocytes in vivo in patients with advanced breast cancer.

Topics: Adult; Aged; Breast Neoplasms; Cell Proliferation; fas Receptor; Female; Glucans; Humans; Leukocyte Common Antigens; Lipopolysaccharide Receptors; Middle Aged; Monocytes

Most current strategies of drug delivery systems face momentous challenges owing to obvious biological barriers. It is urgently necessary to develop artificial nanocarriers with biological and physical properties to reduce the severe system cytotoxicity of chemical drugs. Herein, triggered by the stiffness and amphiphilicity of the triple helix β-glucan (LNT), we developed a novel nanocarrier with the hydrophobic cavity for delivering the anti-cancer drug of doxorubicin. In our findings, based on the law of minimum surface energy, LNT with considerable chain stiffness self-assembled into nanotubes (LNT-NT) with the controlled hydrophobic nanotube diameter at the nanometer level positively depending on the molecular weight through hydrogen bonding and hydrophobic interaction in manners of "shoulder-to-shoulder" and "head-to-head" arrangements. The hydrophobic drug of doxorubicin was then demonstrated to be entrapped into LNT-NT through hydrophobic interaction. Doxorubicin loaded into LNT-NT nanocarriers significantly inhibited tumor growth in vitro and in vivo by promoting tumor cell apoptosis and blocking cell proliferation, showing a higher therapeutic efficacy of 74.5 % and less adverse effects than the free doxorubicin, which was ascribed to the enhanced targetability by LNT-NT. In conclusion, this work proposes an alternative strategy for delivering hydrophobic drugs to reduce cytotoxicity and enhance therapeutic effectiveness by constructing β-glucan-based nanotubes as a promising nanocarrier.

Topics: beta-Glucans; Breast Neoplasms; Doxorubicin; Drug Carriers; Female; Humans; Nanotubes; Polysaccharides

Breast cancer is one of the most threatening cancers that poses a great risk to women's health. The anti-tumor drug doxorubicin (DOX) is one of commonly used drugs in the treatment of breast cancer. However, the cytotoxicity of DOX has always been an urgent challenge to be solved. In this study, we report an alternative drug delivery system delivering DOX for reducing its physiological toxicity by using the yeast β-glucan particle (YGP) with a hollow and porous vesicle structure. Briefly, amino groups were grafted onto the surface of YGP with the silane coupling agent, then the oxidized hyaluronic acid (OHA) was attached by Schiff base reaction to get HA-modified YGP (YGP@N=C-HA), finally DOX was encapsulated into YGP@N=C-HA to get DOX-loaded YGP@N=C-HA (YGP@N=C-HA/DOX). In vitro release experiments exhibited the pH-responsive DOX release from YGP@N=C-HA/DOX. Cell experiments displayed that YGP@N=C-HA/DOX had good killing effect on both MCF-7 and 4T1 cells and could be internalized into these cells through CD44 receptors, showing targetability to cancer cells. Furthermore, YGP@N=C-HA/DOX could effectively inhibit tumor growth and reduce the physiological toxicity of DOX. Thus, the YGP-based vesicle provides an alternative strategy for lowering the physiological toxicity of DOX in the medical treatment of breast cancer.

Topics: beta-Glucans; Breast Neoplasms; Doxorubicin; Drug Delivery Systems; Female; Humans; Hyaluronic Acid; MCF-7 Cells; Nanoparticles; Saccharomyces cerevisiae

Lay abstract We aimed to evaluate the effect of pleuran (β-glucan from oyster mushroom) on the selected immune parameters of patients with breast cancer in remission. We studied antitumor cellular immune parameters of 195 patients (49 in the pleuran group and 146 in the control group) by means of flow cytometry. After 12 months, we measured a significant increase of cytotoxic T lymphocytes in the pleuran group compared with a significant decrease in the control group. Our results suggest potential benefit of long-term administration of pleuran on antitumor cellular immunity and better prognosis in breast cancer patients in remission.

Topics: beta-Glucans; Breast Neoplasms; Female; Humans; Immunomodulation; Middle Aged; Pleurotus

β-glucan from Lentinus edodes (LNT) is a plant-derived medicinal fungus possessing significant bioactivities on anti-tumor. Both hypoxia-induced factor-1α (HIF)-1α and Nur77 have been shown to be involved in the development of breast cancer. However, there is yet no proof of Nur77/HIF-1α involvement in the process of LNT-mediated tumor-inhibition effect.. Immunohistochemistry, immunofluorescence and Hematoxylin-Eosin staining were used to investigate tumor growth and metastasis in MMTV-PyMT transgenic mice. Proliferation and metastasis-associated molecules were determined by Western blotting and reverse transcription-quantitative PCR. Hypoxic cellular model was established under the exposure of CoCl2. Small interference RNA was transfected using Lipofectamine reagent. The ubiquitin proteasome pathway was blunted by adding the proteasome inhibitor MG132.. LNT inhibited the growth of breast tumors and the development of lung metastases from breast cancer, accompanied by a decreased expression of HIF-1α in the tumor tissues. In in vitro experiments, hypoxia induced the expression of HIF-1α and Nur77 in breast cancer cells, while LNT addition down-regulated HIF-1α expression in an oxygen-free environment, and this process was in a manner of Nur77 dependent. Mechanistically, LNT evoked the down-regulation of HIF-1α involved the Nur77-mediated ubiquitin proteasome pathway. A strong positive correlation between Nur77 and HIF-1α expression in human breast cancer specimens was also confirmed.. Therefore, LNT appears to inhibit the progression of breast cancer partly through the Nur77/HIF-1α signaling axis. The findings of the present study may provide a theoretical basis for targeting HIFs in the treatment of breast cancer.

Topics: Adult; Aged; Animals; Antineoplastic Agents; beta-Glucans; Breast Neoplasms; Disease Progression; Female; Fungal Polysaccharides; Gene Expression Regulation, Neoplastic; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Lung Neoplasms; MCF-7 Cells; Mice, Transgenic; Middle Aged; Nuclear Receptor Subfamily 4, Group A, Member 1; Proteasome Endopeptidase Complex; Shiitake Mushrooms; Signal Transduction; Tumor Burden; Ubiquitination

We fabricated a targeted delivery system for doxorubicin (Dox) using β-1,3-glucan (Glu) as a carrier and decorated by trastuzumab antibody having the status of targeting agent against Her2+ breast tumors. Glu-Dox conjugates were also functionalized with polyethylenimine (PEI) intended for increasing specific cellular uptake of prepared nanoparticles. The self-assembled nanoparticles were prepared through conjugation of Dox- [Glu-Dox-] using succinic anhydride (Sa) in place of a linker. Nanoparticles had spherical morphology with positive zeta potential. In-vitro cell viability assay on two breast cancer cell lines demonstrated acceptable toxicity against tested cell lines. Confocal microscopic images demonstrated the remarkable cytoplasmic uptake of the nanoparticles in Her2-overexpressing 4T1 cells. A controlled release of Dox from Glu-Dox nanoparticles was investigated. In-vivo studies were performed on female Balb/C mice. The volume of the induced tumors was calculated following intravenous administration of nanoparticles. The tumor volume diminished efficiently and more rapidly after administration of nanoparticles containing Dox. Based on survival results, the formulation of Dox targeted nanoparticles appeared very promising for the treatment of tumors. It could be concluded that Glu-Dox targeted nanoparticles have potential advantages for delivering anticancer drugs to the target tissue.

Topics: Animals; Antineoplastic Agents; beta-Glucans; Breast Neoplasms; Cell Line, Tumor; Cell Survival; Doxorubicin; Drug Carriers; Drug Liberation; Female; MCF-7 Cells; Mice; Mice, Inbred BALB C; Nanoparticles; Polyethyleneimine; Receptor, ErbB-2; Succinates; Trastuzumab; Tumor Burden

Our studies showed that tumor-infiltrating dendritic cells (DC) in breast cancer drive inflammatory Th2 (iTh2) cells and protumor inflammation. Here, we show that intratumoral delivery of the β-glucan curdlan, a ligand of dectin-1, blocks the generation of iTh2 cells and prevents breast cancer progression in vivo. Curdlan reprograms tumor-infiltrating DCs via the ligation of dectin-1, enabling the DCs to become resistant to cancer-derived thymic stromal lymphopoietin (TSLP), to produce IL-12p70, and to favor the generation of Th1 cells. DCs activated via dectin-1, but not those activated with TLR-7/8 ligand or poly I:C, induce CD8+ T cells to express CD103 (αE integrin), a ligand for cancer cells, E-cadherin. Generation of these mucosal CD8+ T cells is regulated by DC-derived integrin αvβ8 and TGF-β activation in a dectin-1-dependent fashion. These CD103+ CD8+ mucosal T cells accumulate in the tumors, thereby increasing cancer necrosis and inhibiting cancer progression in vivo in a humanized mouse model of breast cancer. Importantly, CD103+ CD8+ mucosal T cells elicited by reprogrammed DCs can reject established cancer. Thus, reprogramming tumor-infiltrating DCs represents a new strategy for cancer rejection.

Topics: Animals; beta-Glucans; Breast Neoplasms; CD8-Positive T-Lymphocytes; Cell Differentiation; Cell Line, Tumor; Cell Transformation, Neoplastic; Dendritic Cells; Disease Models, Animal; Female; Humans; Lectins, C-Type; Mice; Mucous Membrane; Signal Transduction; T-Lymphocyte Subsets; Th2 Cells; Transforming Growth Factor beta

Because of the reported immune-enhancing and anti-tumor activities of some mushroom polysaccharides, their applications as biological response modifiers have attracted significant attention. We have purified a water-soluble beta-glucan PCM3-II, comprising mainly 1right curved arrow 3 and 1right curved arrow 4 linkages, from the mycelia of Poria cocos (Schw.) Wolf (Fu-ling). In this study, the growth-inhibitory effect of PCM3-II was further explored on the human breast carcinoma MCF-7 cells in vitro. The dose effect of PCM3-II was studied by incubating the breast cancer cells with 12.5-400 microg/ml of the glucan for 72 h. The MTT study showed that PCM3-II reduced proliferation and viability of the MCF-7 cells dose-dependently, so that the cancer-cell growth was decreased by 50% of the control level at 400 microg/ml of the glucan. The time effect of PCM3-II was then investigated by treating the breast cancer cells with 400 microg/ml of the glucan for 24, 48 and 72 h, respectively. Results from the flow cytometry study demonstrated that PCM3-II induced cell-cycle G1 arrest time-dependently and about 90% of the cells in cell cycle were accumulated at G1 phase after 72 h of treatment. The G1 arrest was associated with downregulations of the unscheduled cyclin D1 and cyclin E expressions in the breast cancer cells. Apoptosis was also induced by PCM3-II in the MCF-7 cells, so that the subG1 cells in DNA histogram of the flow cytometry were elevated by 5-fold of the control level at 48 h and by 24-fold at 72 h of treatment. The immunoblot study also showed that the glucan induced depletion of the antiapoptotic Bcl-2 protein, but not the proapoptotic Bax protein, so that the Bax/Bcl-2 ratio was elevated in the breast cancer cells at the time when the most prominent apoptosis was also observed. In conclusion, although the detailed mechanism for the anti-tumor activity of the P. cocos beta-glucan still needs further investigation, this study provides preliminary insights into its mode of action and perspectives of its development as a water-soluble anti-tumor agent.

Topics: Apoptosis; bcl-2-Associated X Protein; beta-Glucans; Breast Neoplasms; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cyclin D1; Cyclin E; Dose-Response Relationship, Drug; Down-Regulation; Female; Flow Cytometry; Growth Inhibitors; Humans; Immunoblotting; Mycelium; Polyporales; Proto-Oncogene Proteins c-bcl-2; Time Factors