Published Articles

2015

Arabinoxylan rice bran (MGN-3/Biobran) enhances natural killer cell — mediated cytotoxicity against neuroblastoma in vitro and in vivo

Authors: Anton Pérez-Martínez, Jaime Valentín, Lucía Fernández, Enrique Hernández-Jiménez, Eduardo López—Collazo, Petra Zerbes, Ellen Schworer,Fernando Nuňéz, Inmaculada Génesis Martín, Hannah Sallis, Miguel Ángel Díaz, Rupert Handgretinger & Matthias Manuel Pfeiffer
Journal: Cytotherapy, 2015; 0: 1-12 / International Society for Cellular Therapy

abstract
Abstract: Background aims. Natural killer cell (NK) cytotoxic activity plays a major role in natural immunologic defences against malignancies. NK cells are emerging as a tool for adoptive cancer immunotherapies. Arabinoxylan rice bran (MGN-3/Biobran) has been described as a biological response modifier that can enhance the cytotoxic activity of NK cells. This study evaluated the effect of MGN-3/Biobran on NK cell activation, expansion and cytotoxicity against neuroblastoma cells. Methods. NK cells were enriched with magnetic beads and stimulated with MGN-3/Biobran. NK cell activation was evaluated via analysis of their phenotype, and their expansion capability was tracked. The in vitro cytotoxic ability of the activated NK cells was tested against K562, Jurkat, A673, NB1691, A-204, RD and RH-30 cell lines and the in vivo cytotoxic ability against the NB1691 cell line. Results. MGN-3/Biobran stimulation of NK cells induced a higher expression of the activationassociated receptors CD25 and CD69 than in unstimulated cells (P < 0.05). The expression of NKG2D, DNAM, NCRs and TLRs remained unchanged. Overnight MGN-3/Biobran stimulation increased NK cell cytotoxic activity against all cell lines tested in vitro and decelerated neuroblastoma growth in vivo. The mechanism is not mediated by lipopolysaccharide contamination in MGN-3/Biobran. Furthermore, the addition of MGN-3/Biobran promoted NK cell expansion and decreased T cells in vitro. Conclusions. Our data show that MGN-3/Biobran upregulates NK cell activation markers, stimulates NK cell cytotoxic activity against neuroblastoma in vitro and in vivo and selectively augments the expansion of NK cells. These results may be useful for future NK cell therapeutic strategies of the treatment of neuroblastoma.
2014

MGN-3/BIOBRAN Enhances Generation of Cytotoxic CD8+ T Cells Via Upregulation of DEC-205 Expression on Dendritic Cells

Authors: M. Ghoneum and S. Agrawal
Journal:Journal of Immunopathology and Pharmacology, Vol.27, no.4, 523-530 (2014)

abstract
Abstract: Arabinoxylan rice bran (MGN—3/Biobran) has been shown to be a potent biological response modifier (BRM) that activates different arms of the immune system, including dendritic cells (DCs), which prime CD4+ helper T-cell responses. The present study explores the ability of MGN-3-activated DCs to prime CD8+ T cells and examines the mechanisms underlying its effect. Human monocyte-derived DCs were treated with MGN-3 (20 and 40 µg/ml). Results indicate that treatment with MGN-3 caused DCs to prime higher granzyme B-expressing CD8+ T cells. Tumor lysate-pulsed MGN-3 DC also increased tumor cell killing compared to DC-stimulated CD8+ T cells. This was associated with: i) increased expression of DEC-205 in MGN-3-activated DCs in a dose—dependent manner; and ii) MGN-3 induced significant production of Type III interferon, IL29, but not Type I IFNs on and B. These results suggest that MGN-3 is a potent natural adjuvant that efficiently activates DCs and may therefore be useful for mounting an efficient immune response against infections and cancer.
2014

Therapeutic Effects of Biobran, Modified Arabinoxylan Rice Bran, in Improving Symptoms of Diarrhea Predominant or Mixed Type Irritable Bowel Syndrome: A Pilot, Randomized Controlled Study

Authors: Takeshi Kamiya, Michiko Shikano, Mamoru Tanaka, Keiji Ozeki,Masahide Ebi, Takahito Katano, Shingo Hamano, Hirotaka Nishiwaki, Hironobu Tsukamoto, Tsutomu Mizoshita, Yoshinori Mori, Eiji Kubota, Satoshi Tanida, Hiromi Kataoka, Noriaki Okuda, and Takashi Joh
Journal: Evidence-Based Complementary and Alternative Medicine / Hindawi Publishing Corporation Volume 2014, Article ID 828137, 6 pages

abstract
Abstract: Recently, it was revealed that low grade mucosal inflammation and/or immune imbalance of the lower digestive tract is one of the mechanisms involved in symptom generation in patients with irritable bowel syndrome (IBS). Biobran, arabinoxylan compound derived from rice bran, has been reported to have several biological actions such as anti-inflammatory and immune modulatory effects. So we investigated the therapeutic effects of Biobran in patients with IBS. Method. Forty patientswith diarrhea predominant or mixed type IBS were randomly assigned to either a Biobran group for treatment with Biobran or a placebo group. Therapeutic efficacy and IBS symptoms were assessed subjectively by the patients after 4 weeks of administration. Results. The global assessment was effective in 63.2% of the Biobran group and in 30% of the placebo group (?? < 0.05, Biobran group versus placebo group). Biobran group showed a significant decrease in the score of diarrhea and constipation and in CRP value. However, no significant changes were observed in the placebo group. Conclusion.The administration of Biobran improved IBS symptoms. It is likely that anti-inflammatory and/or immune modulatory effects of Biobran might be useful in IBS patients.
2014

Modified Arabinoxylan from Rice Bran, MGN-3/Biobran, Sensitizes Metastatic Breast Cancer Cells to Paclitaxel In Vitro

Authors: Mamdooh Ghoneum, Nariman K. Badr El-Din, Doaa A. Ali and Mai Alaa El-Dein
Journal: Anticancer Research: International Journal of Cancer Research and Treatment 34: 81-88 (2014) – ISSN: 0250-7005

abstract
Abstract:There is an increased interest in alternative treatments that reduce the toxicity of chemotherapy by lowering the drug concentration, whilst maintaining potency against cancer cells. Previous studies have demonstrated that arabinoxylan from rice bran, MGN-3/Biobran, sensitizes human breast cancer cells (BCC) to daunorubicin (DNR). In the present study, we further evaluated the ability of MGN-3 to sensitize cells to another chemotherapy agent, paclitaxel. Materials and Methods: Non-metastatic MCF-7 (human BCC) and metastatic 4T1 (murine BCC) cells were cultured with different concentrations of paclitaxel in the presence or absence of MGN-3 . Cell survival, DNA damage, and cell proliferation were examined. Results: MGN-3 increased the susceptibility of both types of cancer cells to paclitaxel by over 100-fold. Mechanistically, MGN-3 works synergistically with paclitaxel by causing DNA damage, enhancing apoptosis, and inhibiting cell proliferation in 4T1 cells. Conclusion: Our data demonstrate that MGN-3 is an effective chemosensitizer and may represent a novel adjuvant for the treatment of metastatic breast cancer.
2014

Protective effect of low molecular fraction of MGN-3, a modified arabinoxylan from rice bran, on acute liver injury by inhibition of NF-kB and JNK/MAPK expression

Authors: Surina Zheng, Shunsuke Sugita, Shizuka Hirai, Yukari Egashira
Journal:International Immunopharmacology 14 (2012) 764–769

abstract
Abstract:D-Galactosamine (GaIN) induces acute hepatitis in experimental animals; this hepatitis has been shown to be suppressed by oral or intraperitoneal administration of modified arabinoxylan from rice bran (MGN—3), and active low molecular fraction isolated from MGN-3 (LMW). We previously reported that this protective mechanism is mediated in part by downregulation of interleukin-18 (IL-18), The present study shows for the Hrst time that nuclear factor- ?B (NF- ?B), mitogen-activated protein kinase (MAPK) and CD14 are involved in the suppressive action of LMW on GaIN-induced hepatitis Wistar rats (aged 4 weeks, SLC) were intraperitoneally treated with either MGN—3 or LMW. Then, rats were given GaIN at 400 mg/kg at 1 h after the initial treatment, The serum activity of transaminases (ALT and AST) was significantly higher after GaIN treatment: these changes were attenuated by MGN—3 and LMW. Furthermore, LMW abrogated inhibitor of ?B kinase (I ?B) degradation induced by GaIN, and this was associated with the inhibition of NF ?B activation. Moreover, phosphorylated stress-activated protein kinase/c-jun N-terminal kinase (JNK) protein expression in the liver after GaIN treatment was significantly higher, and LMW reduced this increase. We also found that GaIN treatment induced TLR4 and CD14 mRNA expression, and LMW significantly inhibited CD14 mRNA expression. These results suggest that the suppressive effects of LMW on GaIN—induced hepatitis are possibly related to inhibition of NF- ?B,NK phosphorylation and CD14 expression.
2013

Arabinoxylan rice bran (MGN-3/Biobran) provides protection against
whole-body γ-irradiation in mice via restoration of hematopoietic tissues

Authors: Mamdooh Ghoneum, Nariman K. Badr El-Din, Salma M. Abdel Fattah and Lucilene Tolentino
Journal: Journal of Radiation Research, 2013, 00, 1–11 doi: 10.1093/jrr/rrs119.

abstract
Abstract:The aim of the current study is to examine the protective effect of MGN-3 on overall maintenance of hematopoietic tissue after ƴ-irradiation. MGN-3 is an arabinoxylan from rice bran that has been shown to be a powerful antioxidant and immune modulator. Swiss albino mice were treated with MGN-3 prior to irradiation and continued to receive MGN-3 for 1 or 4 weeks, Results were compared with mice that received radiation (5 Gy rays) only, MGN-3 (40 mg/kg) only and control mice (receiving neither radiation nor MGN-3). At 1 and 4 weeks post-irradiation, different hematological, histopathological and biochemical parameters were examined. Mice exposed to irradiation alone showed significant depression in their complete blood count (CBC) except for neutrophilia. Additionally, histopathological studies showed hypocellularity of their bone marrow, as well as a remarkable decrease in splenic weight/relative size and in number of megakaryocytes. In contrast, pre-treatment with MGN-3 resulted in protection against irradiation-induced damage to the CBC parameters associated with complete bone marrow cellularity, as well as protection of the aforementioned splenic changes. Furthermore, MGN-3 exerted antioxidative activity in whole-body irradiated mice, and provided protection from irradiation-induced loss of body and organ weight. In conclusion, MGN-3 has the potential to protect progenitor cells in the bone marrow, which suggests the possible use of MGN-3/Biobran as an adjuvant treatment to counteract the severe adverse side effects associated with radiation therapy.
2013

Case Reports of Cancer Patients with Hepatic Metastases Treated by Standardized Plant Immunomodulatory Preparations

Authors: Tibor Hajto and Angelika Kirsch
Journal: Journal of Cancer Research Updates, 2013, 2, 000-000

abstract
Abstract:Background: Metastatic hepatocellular carcinoma often has a multifocal tumor pattern with markedly depressed hepatic function, Hepatic resection in many cases results in no long-term benefit. After a chemotherapy hepatic tumors rarely disappear completely and the duration of responses is short, ln the last decades growing evidence suggested that a disturbed balance in the innate system can also play a role in the poor prognosis of hepatic tumors.
Objectives: The aim of this article is to present and discuss several favorable clinical responses of patients with hepatic metastases who parallel to conventional oncologic therapy, were treated with immunologically effective and standardized plant extracts.
Course of Therapy and Results: In accordance with the bell-shaped dose-response relationship of mistletoe Iectins (MLs), the patients were treated with a fermented mistletoe extract (ME) preparation, standardized for the active sugar-binding lectin contents, Thus, an optimal dose between 0.5 and 1,0ng/kg MLs was given twice a week subcutaneously. In addition to ML therapy, a heteropolysaccharide rice bran preparation standardized for arabinoxylan (12-45mg/kg MGN-3/Biobran twice a week) and wheat germ extract (WGE) standardized for 2, 6-dimethoxy-p-benzoquinone (50-80mg/kg AvemarR four times a week) was also given. In these case reports the clinical progress of seven patients showed a complete or nearly complete remission of hepatic metastases.
Conclusion: ML, MGN-3 and WGE seem to be potent candidates to be regarded as a supportive therapy to surgery, hormone treatment or chemotherapy for patients with hepatic metastases. These case reports require further clinical studies.”
2013

Biobran MGN-3: Effect of reducing side effects of chemotherapy in breast cancer patients

Authors: Masood AI, Sheikh R, Anwer RA
Journal: Professional Med J Feb 2013;20(1):013-016.

2012

Protective effect of low molecular fraction of MGN-3, a modified arabinoxylan from rice bran, on acute liver injury by inhibition of NF-kB and JNK/MAPK expression

Authors: Surina Zheng, Shunsuke Sugita, Shizuka Hirai, Yukari Egashira
Journal: International Immunopharmacology 14 (2012) 764-769

abstract
Abstract:D-Galactosamine (GaIN) induces acute hepatitis in experimental animals; this hepatitis has been shown to be suppressed by oral or intraperitoneal administration of modified arabinoxylan from rice bran (MGN—3), and active low molecular fraction isolated from MGN-3 (LMW). We previously reported that this protective mechanism is mediated in part by downregulation of interleukin-18 (IL-18), The present study shows for the Hrst time that nuclear factor- ?B (NF- ?B), mitogen-activated protein kinase (MAPK) and CD14 are involved in the suppressive action of LMW on GaIN-induced hepatitis Wistar rats (aged 4 weeks, SLC) were intraperitoneally treated with either MGN—3 or LMW. Then, rats were given GaIN at 400 mg/kg at 1 h after the initial treatment, The serum activity of transaminases (ALT and AST) was significantly higher after GaIN treatment: these changes were attenuated by MGN—3 and LMW. Furthermore, LMW abrogated inhibitor of ?B kinase (I ?B) degradation induced by GaIN, and this was associated with the inhibition of NF ?B activation. Moreover, phosphorylated stress-activated protein kinase/c-jun N-terminal kinase (JNK) protein expression in the liver after GaIN treatment was significantly higher, and LMW reduced this increase. We also found that GaIN treatment induced TLR4 and CD14 mRNA expression, and LMW significantly inhibited CD14 mRNA expression. These results suggest that the suppressive effects of LMW on GaIN—induced hepatitis are possibly related to inhibition of NF- ?B,NK phosphorylation and CD14 expression.
2012

MGN-3 arabinoxylan rice bran modulates innate immunity in multiple myeloma patients

Authors: Danna Cholujova, Jana Jakubikova, Brarnislav Czako, Michaela Marisova, Luba Hunakova, Jozef Duraj, Martin Mistrik, Jan Sedlak.
Journal: Cancer Immunology, Immunotherapy DOI 10.1007/s00262-012-1344-z

2012

An Open-label, randomized clinical trial to assess the immunomodulatory activity of a novel olgosaccharide compound in healthy adult

Authors: K. H. Ali, A. B. Melillo, S. M. Leonard, D. Asthana, Judi M. Woolger, A. H. Wolfson, H. R. McDaniel, J. E. Lewis
Journal: Functional Foods in Health and Disease 2012, 2(7): 265-279

abstract
Abstract:Rice Bran Arabinoxylan Compound (RBAC) is a nutritional supplement produced by enzymatic hydrolysis of hemicellulose B derived from rice bran. Several in vitro studies and clinical reports have shown RBAC to possess promising immunomodulating effects, specifically with respect to natural killer cell and cytokine activity. The concept of a true immunomodulator is an agent possessing a broad range of activity dependent upon the existing state of health and immunity in the individual host. The present study investigated the immunomodulatory effect of RBAC in a healthy adult human population over 60 days by assessing changes in natural killer cell cytotoxicity (NKCC) and cytokines and growth factors. Subjects participated in a two-group, randomized intervention, where one group (n=10) consumed 1 gram/day and the other (n=10) consumed 3 gram/day. Safety and tolerability of RBAC were assessed with total bilirubin, total protein, creatinine, and liver function tests.
2012

Chemopreventive Properties of Dietary Rice Bran: Current Status and Future Prospects

Authors: Angela J. Henderson, Cadie A. Ollila, Ajay Kumar, Erica C. Borresen, Komal Raina, Rajesh Agarwal and Elizabeth P. Ryan.
Journal: Advances in Nutrition, Sept 2012, Vol 3: 643-653.

2012

Suppressive Effect of Modified Arabinoxylan from Rice Bran (MGN-3) on D-Galactosamine-Induced IL-18 Expression and Hepatitis in Rats

Authors: S. Zheng, H. Sanada, H. Dohi, S. Hirai and Y. Egashira
Journal: Bioscience / JSBA (Japan Society for Bioscience, Biotechnogy and Agrochem) 76 (5), 942-946, 2012

abstract
Abstract:We investigated in this study the effect of modified arabinoxylan from rice bran (MGN-3) and its fractions on D-galactosamine (D-GalN)-induced IL-18 expression and hepatitis in rats. Male Wistar rats were pretreated with MGN-3 or fractions of the MGN-3 hydrolysate, or with saline 1 h before administering D-GalN (400 mg/kg B.W.). The serum transaminase activities, IL-18 mRNA expression level in the liver and IL-18 concentration in the serum were determined 24h after injecting D-GalN. Both the oral and intraperitoneal administration of MGN-3 (20 mg/kg B.W.) alleviated D-GalN-induced hepatic injury under these experimental conditions. The low-molecular-weight fraction (LMW) of MGN-3 showed the strongest protective effect on D-GalN-induced liver injury, its main sugar component being glucose. Moreover, the D-GalN-induced IL-18 expression was significantly reduced by treating with MGN-3 and LMW. The results suggest that MGN-3 and LMW could provide significant protection against D-GalN liver injury, and that IL-18 might be involved in their protective influence.
2011

Synergistic apoptotic effect of Arabinoxylan rice bran (MGN-3/Biobran) and Curcumin (Turmeric) on human multiple myeloma cell line U266 invitro

Authors: M. Ghoneum, S. Gollapudi
Journal: Neoplasma 58, 2, 2011

abstract
Abstract:The present study was carried out to investigate the synergistic apoptotic potential of arabinoxylan rice bran (MGN-3/Biobran) and curcumin (turmeric) on human multiple myeloma (MM) cell line U266 , in vitro. U266 cells were cultured with MGN-3 (50 or 100µg/ml) and curcumin (2.5-10µM) for 3 days. The elfects of MGN-3 and curcumin on the growth and survival of the U266 cells were determined by trypan blue, MTT assay flow cytometry analysis of cancer cell cycle, and apoptosis. Expression of proapoptotic Bax, and antiapoptotic Bcl2 was determined by Western blot analysis. Treatment with MGN—3 alone or curcumin alone caused a dose-dependent inhibition in the proliferation ofU266 cells. However, a synergistic elfect was noticed post-treatment with both agents that maximized at 100µg/ml MGN-3 plus 10µM curcumin. This synergy was characterized by an 87% decrease in cell number and a 2.6 fold increase in the percentage of apoptotic U266 cells, Cell cycle analysis showed a 53% decrease in the percentage ofcells in the G0-G1 phase treated with MGN-3 and curcumin (from 36% to 17%). Analysis ofthe expression of the pro and antiapoptotic molecules Bax and Bcl-2 revealed synergistic effects of these agents, as the expression of Bcl-2 was decreased and Bax was increased. This resulted in a cellular microenvironment favorable for apoptosis. We conclude that MGN-3 and curcumin synergize in the induction of U266 cell apoptosis. This data may establish the foundation for in viva studies that could have therapeutic implications.
2011

The clinical effectiveness of BioBran in immunotherapy for patients with hepatitis B

Author: Dr. Tran Thi Minh Phuong

abstract
Abstract:Hepatitis B virus (HBV) infection is a serious global health problem with devastating consequences of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. More efficacious treatments, mass immunization programs, and safe injection techniques are essential for eliminating HBV infection and reducing global HBV-related morbidity and mortality. Antiviral therapy has been the primary treatments to date. However, conventional treatment has undesirable side-effects and continuous treatment can lead to the development of resistance. In addition, antiviral medicines are costly, thousands of dollars per year, and are not widely available in many countries, especially in the developing world. BioBran is a food supplement that is combined with conventional treatment to improve the outcome of the disease. There were 3 cases of viral B hepatitis patients who have treated by the combination of conventional antiviral therapy and BioBran were described. In these cases, blood samples were taken to measure liver function and immunopotency, and the results were compared with changes in clinical and image condition. Improvements were noted in most of the cases. Finally, some remarks were provided to enhance the effectiveness of treatment progress.
2011

Activation of Human Monocyte-Derived Dendritic Cells In Vitro by the Biological Response Modifier Arabinoxylan Rice Bran (MGN-3/Biobran)

Authors: M. Ghoneum and S. Agrawal
Journal: Journal of Immunopathology and Pharmacology, Vol.24, no.4, 941-948 (2011)

abstract
Abstract:Arabinoxylan rice bran (MGN—3/Biobran) is a potent biological response modifier (BRM) that activates natural killer (NK) cells, T cells and monocytes. Currently, little is known regarding the effects of MGN-3 on dendritic cells (DCs), the cell type that bridges innate and adaptive immunity. Therefore, we examined the stimulatory effects of MGN-3 on DCs. Human monocyte-derived DCs were treated with MGN-3 at different concentrations (5-20 µg/ml) for 24 hours in vitro. Activation of DCs was determined by assessing the expression of co-stimulatory and maturation markers (CD40, CD80, CD83, CD86 and HLA-DR) by flow cytometry, and production of cytokines by ELISA. DC function was determined by assessing their ability to activate naive T cells. Activation of T cells was assessed by measuring cell proliferation and cytokine production. MGN-3 treatment, in a dose-dependent manner, resulted in: 1) up-regulation of the surface expression of CD83 and CD86, on DCs; 2) an increase in the production ofpro-inflammatory and immuno—regulatory cytokines (IL-lß}, IL-6, IL-10, TNF-a, IL-12p40 and low levels of IL-12p70 and IL-2) by DCs; and 3) MGN-3 stimulated DC induced CD4T cell proliferation and their production of cytokines, IFN-7, lL-10, IL-17. Results suggest that MGN-3 functions as a natural adjuvant for DC activation and thus may be used in DC-based vaccine strategies against infections and cancer.
2010

Biobran-augmented maturation of human monocyte derived dendritic cells

Authors: Mai Hong Bang, Mamdooh Ghoneum
Journal: AntiCancer Research 30: 5145-5152 (2010)

2010

Arabinoxylan Rice Bran (MGN-3) Enhances the Effects of Interventional Therapies for the Treatment of Hepatocellular Carcinoma: A Three-year Randomized Clinical Trial

Authors: Mai Hong Bang, Tran Van Piep, Nguyen Tien Thinh, Le Huu Song, Trinh Tuan Dung, Le Van Truong, Le Van Don, Thai Doan Ky, Deyu Pan, Magda Shaheen and Mamdooh Ghoneum
Journal: Anticancer Research 30: 5145-5152 (2010).

abstract
Abstract:Background and Aims: This study examined the efficacy of arabinoxylan rice bran (MGN-3) in conjunction with an interventional therapy (IT) for the treatment of hepatocellular carcinoma patients. Patients and Methods: A total of sixty-eight patients with hepatocellular carcinoma (stages I and II) participated in the study. Patients were randomized to receive IT (30 patients, control group) or IT+MGN-3 (38 patients), and randomly divided into two groups using a computer-generated randomization list. Patients and investigators were blinded. IT included transarterial oily chernoembolization (TOCE) or a combination of TOCE and percutaneous ethanol injection treatment (PEIT). Results: Patients in the IT+MGN-3 group showed: (i) lower recurrence ofthe disease, 3l.6% (I2/38), as compared to 46.7% (I4/30) for the control; (ii) higher survival aher the second year, 35%, as compared to 6.7% for the control; (iii) significantly lower alpha-fetoprotein level, a 38% decrease (p=0,()001), as compared to baseline value, while the control showed no signficant change; and (iv) a significant decrease in tumor volume, in contrast to the control, which showed no significant change. When the results were analyzed according to each IT modality, MGN-3+IT sub-groups displayed a greater response to treatment, in every aspect examined, than the IT sub-groups alone, Howeven the patients in the MGN-3+TOCE+PEIT sub-group demonstrated greater reduction in AFP levels and longer survival time than the MGN-3+TOCE; sub-group. Conclusion: MGN-3 in conjunction with IT may be usefaljbr the treatment of hepatocellular carcinoma and warrants farther investigation in multiple clinical trials.
2009

Biobran-augmented maturation of human monocyte-derived dendritic cells

Authors: D. Cholujova, J. Jakugikova, J. Sedlak
Journal: Neoplasma 56, 2, 2009.

abstract
Abstract:BioBran, enzymatically modified arabinoxylan from rice bran was tested for its possible effects on in vitro matumtion of human dendritic cells (DC). lmmature DC (iDC) derived from plastic-adhered, lL-4 and GM-CSF treated peripheral monocytes (Mo) were further cultured with cytokine maturation mix l (CMMl; TNF-ot, lL-1[5 and 1L»6) or CMM2 (LPS a.nd IFN-Y) to induce their maturation into mature DC (matDCl or matDC2, respectively), Different concentrations of BioBran (10, 100, 400 and 1000 ttgml) were applied in the presence or absence of relevant CMM to assess the effects of BioBran on DC maturation processes. BioBran induced maturation of iDC, as these cells cultured with IL—4/GM—CSF/BioBran down-regulated CDI4 and CDla antigens on cell surface and significantly increased expression of maturation marker CD83. The increase of surface density of costimulatory molecules CD80 and CD86 on iDC in the presence of BioBran was also observed. In addition, BioBran induced functional maturation of iDC, confirmed by decreased endocytic activity of iDC, Furtheremore, BioBran enhanced maturation potential of cytokine mixes, as both matDC1 and matDC2 exposed to BioBran completely lost CD 14 and upregulated CD83, CDS0 and CD86 antigens. in comparison to DC matured with the relevant CMM alone. BioBran also increased CD123 antigen expression on all DC subsets. Interestingly, matDC2 matured in the presence of BioBran (400µg/ml) expressed higher levels of CD123 and lower levels of CD11c cell surface antigens, the phenotype represented by CD11c CD123 plasmacytoid DC population. These data demonstrate that BioBran is a potent enhancer of DC maturation and suggest that BioBran might be a useful agent to create the environment that favours DC maturation.
2008

Epigenetics and Immurmsenescence Reversal: An Evidence-Based Longevity Paradigm

Author: Karriem H. Ali, M.D.

abstract
Abstract:Humankind has long thought of aging as a gradual, time—dependent, deterioration in one‘s well-being and quality of life, with an increased incidence and severity of debilitating chronic diseases. However, current medical opinion argues for a fresh, and more enlightened perspective on aging. Indeed, until recently, clinical medicine has focused more upon mitigating the effects of aging rather than reversing the process itself. However, current developments in epigenetics and immunology mean that we are now ready to begin the greater challenge of halting or reversing the aging process. There is a vast body of scientific literature indicating that immune dysregulation — specifically of the innate immune system — may be the determinative factor for the seemingly inevitable functional decline of advancing age. This dysregulation is characterized by a continual, low—grade, over-reactive state of systemic immune processes, which promote, in whole or in part, the pathognomonic signs of many of the chronic diseases that we associate with aging (e.g., cardiovascular disease, Alzheimer’s disease, cancer, osteoarthritis, insulin—resistance, and diabetes).
2008

Comparative study of four flourescent probes for evaluation of natural killer cell cytotoxicity assays

Authors: Cholujova, Jakubikova, Kubes, Arendacka, Sapak, Robert, Sedlak
Journal: Immunobiology – 2008; 213(8):629-40.

2008

Modulation of the anticancer immunity by natural agents: inhibition of Tregulatory lymphocyte generation by arabinoxylan in patients with locally limited or metastatic solid tumors

Authors: P. Lissoni, G. Messina, F. Brivio, L. Fumagalli, L. Vigore, F. Rovelli, L.Maruelli, M. Miceli, P. Marchiori, G. Porro, M. Held, G. di Fede, T Uchiyamada
Journal: Cancer Therapy Vol 6, 1011-1016.

2008

MGN-3/Biobran, modified arabinoxylan from rice bran, sensitizes human breast cancer cells to chemotherapeutic agent, daunorubicin

Authors: S. Gollapudi and M. Ghoneum
Journal: Cancer Detection and Prevention 32 (2008) 1-6.

abstract
Abstract:MGN-3/Biobran, a modified form of arabinoxylan from rice bran, is a potent biological response modifier (BRM). Our previous studies demonstrated that MGN-3 sensitizes human leukemia cells to death receptor [CD95]-induced apoptosis [Ghoneum M, Gollapudi S. MGN-3 sen sitizes human T cell leukemia cells to death receptor (CD95)-induced apoptosis. Cancer Lett 2003;20l :41-9]. In this study, we evaluated the chemo-sensitizing activity of MGN-3 against human breast cancer cells (BCCs) in vitro. Methods: BCCs (MCF-7 and HCC70 cells) were cultured with different concentrations of daunorubicin (DNR) (from 1 x10?? to 1×10?6M) in the presence or absence of selected concentrations of MGN-3 (100—1000 µg/ml) for 3 days. Cancer cell survival was determined by MTT assay and drug accumulation was determined by flow cytometry. Results: Treatment with MGN-3 increased susceptibility of BCCs to DNR (5.5 –fold for MCF-7 and 2.5-fold for HCC70 cells) as compared to BCCs treated with DNR alone. The sensitizing effect of MGN-3 was associated with increased accumulation of DNR in cancer cells. Conclusions: Our data demonstrate that MGN-3 is an effective chemo-sensitizer and may represent a potential novel adjuvant for the treatment of breast cancer.
2008

Synergistic Role of Arabinoxylan Rice Bran (MGN-3/Biobran) in S. cerevisiae-induced Apoptosis of Monolayer Breast Cancer MCF-7 Cells

Authors: M. Ghoneum and S. Gollapudi
Journal: Anticancer Research 25: 4187-4196.

2008

Modified Arabinoxylan Rice Bran (MGN-3/Biobran) Enhances Intracellular Killing of Microbes by Human Phagocytic Cells In Vitro

Authors: M. Ghoneum, M. Matsuura and S. Gollapudi
Journal: International Journal of Immunopathology and Pharmacology Vol. 21,no. 1, 87-95

abstract
Abstract:Phagocytic cells, comprised of neutrophils and moncytyes/macrophages, play a key role in the innate immune response to infection. Our earlier study demonstrated that arabinoxylan rice bran (MGN-3/Biobran) activates murine peritoneal macrophage and macrophage cell lines. ln this study, we investigated whether MGN-3 can upregulate the phagocytic activity of human phagocytes in peripheral blood to phagocytize Escherichia coli (E. coli), trigger the oxidative burst and produce cytokines. Phagocytic cells were pre-labeled with dichlorofluorescin diacetate dye and were incubated with phycoerythrin-labeled. E. coli in thc presence or absence of MGN-3. Phagocytosis and oxidative burst were assessed by flow cytometry. Results showed that treatment with MGN-3 enhanced the phagocytosis of E. coli by neutrophils and moncytes. This was associated with an increased oxidative burst. ln addition, it caused a significant induction of cytokines (TNF-a, IL-6, IL-8 and lL—10); the effect was detected at 1 µg/ml and increased in a dose—dependent manner (P5 0.01). Notably, MGN-3 alone had no effect on the growth of 31 strains of bacteria suggesting that MGN-3 modulates phagocytic cellular function. These findings may have applications in the treatment of infections in the elderly and in immunocompromised patients.
2008

In Vivo Tumor Inhibitory Effects of Nutritional Rice Bran Supplement MGN-3/Biobran on Ehrlich Carcinoma-Bearing Mice

Authors: N. El-Din, E. Noaman and M. Ghoneum
Journal: Nutrition and Cancer, 60(2), 235-244

abstract
Abstract:This study was undertaken to investigate the in vivo anti-tumor activity of MGN-3/Biobran, a modified arabinoxylan rice bran. Swiss albino mice were inoculated intramuscularly in the right thigh with Ehrlich ascites carcinoma (EAC) cells. On Day 8, mice bearing a solid Ehrlich carcinoma (SEC) tumor were treated with MGN-3 via intraperitoneal injection. Tumor growth, cytokine pro-duction, and apoptotic effect of MGN-3 were examined. MGN-3 caused a highly significant delay in both tumor volume (63.27%) and tumor weight (45.2%) as compared to controls (P < 0.01). The mechanisms by which MGN-3 exerts its antitumor effect seem to involve its ability to induce apoptosis and immune modulation. MGN-3 induced a 1.8-fold increase in the percentage of apoptotic SEC cells as determined by flow cytometry and the histopathological examination. In addition, MGN-3 influenced plasma cytokine production by increasing the levels of tumor necrosis factor-az and interferon-? , while downregulating levels of the immune suppressing cytokine interleukin-10. Data also showed that non-tumor-bearing mice intramuscularly injected with MGN-3 resulted in a twofold increase in natural killer activity. No adverse side effects due to MGN-3 treatment were observed; all animals displayed normal feeding/drinking and life activity patterns. These data may have clinical implications for the treatment of solid cancers.
2007

Yeast Therapy For the Treatment of Cancer and its Enhancement by MGN-3/Biobran, an Arabinoxylan Rice Bran

Authors: M. Ghoneum, J. Brown and S. Gollapudi
Journal: Cellular Signaling and Apoptosis Research pp 185-200 / Chapter VI

abstract
Abstract:Apoptosis constitutes a strictly programmed device for the removal of aged, damaged and abnormal cells. Research in the last decade has revealed a promising future for apoptosis-based cancer therapies. However, chemotherapeutic agents exhibit an indiscriminative killing that involves both cancer cells and many normal cells. It is therefore of particular interest to find agents that have the ability to induce apoptotic activity specifically in cancer cells and with minimal side-effects. Interest in microbe-based approaches to cancer therapy has recently reemerged. The use of S. cerevisiae, the baker’s yeast, as a novel approach for the treatment of cancer is based on the concept that tumor cells undergo apoptosis upon phagocytosis of yeast. Our data shows that: 1) Heat killed yeast induces apoptosis in multiple human cancers [e.g. breast, tongue and colon] in vitro, 2) yeast has no toxicity against normal cells, 3) induction of apoptosis is yeast-specific, 4) apoptotic activity of yeast in cancer cells is enhanced by MGN-3/biobran, a biological response modifier, and importantly, 5) the phenomenon of yeast induced apoptosis was observed in vivo in athymic nude mice model. Electron microscopic studies of tissue samples obtained from in vivo yeast—treated tumors clearly show tumor cells phagocytize yeast and then undergo apoptosis. The molecular mechanism underlying this phenomenon is currently under investigtion in our laboratory. Further investigation into this area may present clinical implications for the treatment of cancer.
2006

Apoptosis of Breast Cancer MCF-7 Cells In Vitro is Induced Specifically by Yeast and Not by Fungal Myceli

Authors: M. Ghoneum and S. Gollapudi
Journal: Anticancer Research 26: 2013-202

abstract
Abstract:lt was recently demonstrated that breast cancer cell lines undergo apoptosis following phagocytosis of S. cerevisiae. The present study was undertaken to determine whether other strains of fungi also induce apoptosis in cancer cells. Eight strains of yeast: C. albicans, C. krusei, C. glabrata, C. kefyr, C. neoformans, Y lipolytica, S. cerevisiae and R. rubra, were evaluated at different developmental stages (small yeast cells, large yeast cells and pseudohyphae). In addition, conidia from I four strains of fungal mycelia: Aspergillus, Aspergillus sp., T rubrum and T tonsurans were evaluated. Breast cancer MCF-7 cells in monolayer were cultured with fungi at a ratio of 1:10, respectively, after which phagocytosis and fungi-induced apoptosis of MCF-7 cells were examined. The MCF-7 cells were found to phagocytize all strains of heat-/cilled yeast, regardless of their evelopmental stage. Phagocytosis followed a graduated series: C. krusei > C. glabrata > R. rubra > S. cerevisiae > C. kefyr > C. neoformans > C. albicans > Y. lipolytica. Yeast-induced apoptosis also followed a graded pattern: S. cerevisiae > C. kefyr > C. krusei > C. neofonmans > R. rubra > C. albicans > C. glabrata > Y. lipolytica, as examined by flow cytometry. In contrast, MCF-7 did not phagocytize or undergo apoptosis post-culture with conidia. This data may have clinical implications for the treatment of breast cancer.
2006

Metastatic Hemangiopericytoma of the Skin Treated with Wide Local Excision and MGN-3

Authors: J Markus, A. Miller, M. Smith, I. Orengo
Journal: Dermatological Surgery 32:1:January

abstract
Abstract:This case report describes an uncommon tumor treated with an unproven medication found by the patient during an Internet search. MGN-3 is an arabinoxylane derived from rice bran that has been enzymatically modified by an extract of the mushroom Hypbomycetes mycelicz. ln vivo murine studies have reported increased natural killer cell activity with MGN-3 supplementation. An in vitro investigation revealed increased tumor necrosis factor or and interferon-y production by peripheral blood lymphocytes treated with MGN-3. In addition, MGN-3 was found to enhance anti-CD95 antibody-induced apoptosis in a human leukemic cell line. This biologic response modifier has been studied in a limited number of patients With human immunodeficiency virus (HIV) disease or cancer, with improvement in natural killer cell function and disease activity over time. Further studies are needed, however, to ascertain the therapeutic benefits of this relatively novel compound.
2005

A case where immunomodularity food and anti-oxidant therapy ws effective in a case of advanced prostate cancer

Author: Dr. Serge Jurasunas of the Holiterapias Institute in Portugal.

2005

Synergistic Role of Arabinoxylan Rice Bran (MGN-3/Biobran) in S.cerevisiae-induced Apoptosis of Monolayer Breast Cancer MCF-7 Cells

Authors: M. Ghoneum and S. Gollapudi
Journal: Anticancer Research vol25: 4187-4196

abstract
Abstract:We have recently demonstrated that breast cancer cell (BCC) lines undergo apoptosis following phagocytosis of S. cerevisiae. Arabinoxylan rice bran extract (MGN-3/Biobran) has been shown to enhance this effect. Since previous data were obtained using cells in suspension, the present study was undertaken to examine monolayer BCC that more closely model cancer cell growth. Monolayers of both breast cancer (MCF-7) and non-tumorgenic breast epithelial (MCF-10A) cells grown on glass coverslips were cultured with heat-killed S. cerevisiae at a ratio of 1:10, respectively. MCF-7 cells phagocytized yeast in a time-dependent manner, 6.9% to 14.3% from 1 h to 4 h, respectively, with a 2-fold increase in the presence of MGN-3. On the other hand, there was virtually no phagocytosis of yeast by MCF-10A cells. Similarly, yeast-induced apoptosis of MCF-7 cells occurred in a time-dependent manner from 11.5% after 1 h to 21. 7% after 4 h, and was enhanced in the presence of MGN-3. These data may have implications in the treatment of breast cancer.
2005

Human Squamous Cell Carcinoma of the Tongue and Colon Undergoes Apoptosis upon Phagocytosis of Saccharomyces Cerevisiae, the Baker’s Yeast, In Vitro

Authors: M. Ghoneum, J. Hamilton, J. Brown, S. Gollapudi
Journal: Anticancer Research vol 25: 981-990

2005

Modified Arabinoxylan Rice Bran (MGN-3/Biobran) Enhances Yeast-induced Apoptosis in Human Breast Cancer Cells In Vitro

Authors: M. Ghoneum and S. Gollapudi
Journal: Anticancer Research vol 25: 859-870

abstract
Abstract:We have recently reported that phagocytosis of killed Saccharomyces cerevisiae, baker’s yeast, induced apoptosis in human breast cancer cell lines MCF-Z, ZR- 75-1 and HCC70. In this study we have evaluated the ejfect of treatment with MGN-3, a modified arabinoxylan from rice bran, on phagocytosis and yeast-induced apoptosis in breast cancer cells. Cancer cells were cultured with yeast at a ratio of 1:10 in the absence or presence of MGN-3, and the percentages of phagocytic and apoptotic cancer cells were examined by flow cytometry and by cytospin preparations. Cancer cells treated with MGN-3 exhibited increased percentages of attachment (200%) and uptake of yeast (313%) by MCF-7 cells at 0.5 hr, as compared with cells without MGN-3. In addition, treatment with MGN-3 resulted in a 2 fold increase in the percentage of apoptotic MCF-7 cells, 2.5 fold for ZR-75 cells and 1.8 fold for HCC70 cells. MGN-3 effect was dose-dependent and associated with increased activation of caspases 8 and 9 in MCF-7 cells, and caspases 8, 9 and 3 in HCC70 cells. This data demonstrates that MGN-3 accelerates phagocytosis-induced apoptosis of cancer cells, which may represent a novel therapeutic strategy for the treatment of breast cancer.
2004

Induction of apoptosis in breat cancer cells by Saccharomyces Cerevisiae, the Baker’s Yeast, in vitro

Authors: M. Ghoneum and S. Gollapudi
Journal: Anticancer Research vol 24: 1455-1464.

abstract
Abstract:The present study was undertaken to evaluate the effect of phagocytosis of killed yeast on the induction of appoptosis in human metastatic breast cancer cells (MCF-7 and ZR-75-1) and non-metastastatic breast cancer cells (HCC70). Heat-killed Saccharomyces cerevisiae, baker’s yeast and brewer’s yeast, was cultured with cancer cells at a ratio of yeast to cancer cells = 10:1, and the percent apoptotic cancer cells was determined by flow cytometry and cytospin preparation. Upon phagocytosis of yeas, breast cancer cells underwent apoptosis. Induction of apoptosis was time and dose- dependent. Apoptosis was detected as early as 0.5 h (13%), increased to 19% at 2 h and peaked (38%) at 4 h. Metastatic cancer cells were found to be more susceptible to yeast-induced apoptosis than non-metastatic cells; 629% increase for MCF-7 as compared to cells alone, 258% for ZR-75 cells, while HCC70 cells showed a 178% increase. Phagocytosis is associated with the disruption of mitochondrial membrane potential and activation of initiator and effector caspases 8, 9 and 3. However, inhibitors of these caspases did not inhibit yeast-induced apoptosis in cancer cells by a mechanism that is independent of caspase activation. This data may have clinical implications.
2004

Enhancement of natural killer cell activity of aged mice by modified arabinoxylan rice bran (MGN-3 /Biobran)

Authors: M. Ghoneum and S. Abedi
Journal: Journal of Pharmacy and Pharmacology (56: 1581-1588).

abstract
Abstract:The present study is aimed to examine the possibility of enhancement of natural killer (NK) cell activity in aged C57BL/6 and C3H mice using MGN-3, a modified arabinoxylan from rice bran. Intraperitoneal injection of MGN-3 (10 mg kg¯¹ per day) caused a remarkable increase in the perito-neal NK activity as early as 2 days (35.2 lytic units), and the level remained elevated through day 14. The control aged mice had a level of 5.8 lytic units. Enhancement in NK activity was associated with an increase in both the binding capacity of NK cells to tumour targets and in the granular content as measured by BLT-esterase activity. Treatment did not alter the percentage of peritoneal NK cells. Data showed that peritoneal macrophages inhibit NK activity. In conclusion, MGN-3 enhances murine NK activity of aged mice and may be useful for enhancing NK function in aged humans.
2004

Experience with Administration of Biobran in Patients with Chronic Rheumatism

Author: Kenichi Ichihashi (Ichihashi Clinic)
Journal: Clinical Pharmacology and Therapy Vol. 14/No.4

abstract
Abstract:The functional food, rice bran arabinoxylan derivative (BioBran), was administered for a long period to patients with chronic rheumatism given mainly symptomatic treatments with steroids, to evaluate its supplementary effect with representative treatments for rheumatism, such as steroids, analgesics, and themiotherapy. Steroids are essential for treatment of rheumatism, but it is desirable to minimize the dose, because they may cause adverse reactions. In recent years, there have been many reports on the functions of food ingredients, including superoxide scavenging and biophylaxis improving actions. This study evaluated the efficacy of BioBran, a functional food material. BioBran has been reported to have the effects of activating natural killer cells (NK cells) and inhibiting inflammation. The author confirmed and reported that it relieved cold symptoms in the elderly. The present study, where 8 patients with chronic rheumatism were given BioBran for 6 to 12 months, demonstrated the improvements of symptoms and QOL, suggesting its effectiveness.
2004

Oral administration of hydrolyzed rice bran prevents the common cold syndrome in the elderly based on its immunomodulatory action

Authors: H. Maeda, K. lchihashi, T. Fujii, K. Omura, X. Zhu, M. Anazawa and K. Tazawa
Journal: BioFactors 21 (2004) 185-187

abstract
Abstract:The preventive effect of Hydrolyzed Rice Bran against the common cold syndrome was examined in elderly people. Arabinoxylan derivatives of Hydrolyzed Rice Bran (HRB) were prepared from water-soluble rice bran through partial processing using a carbohydrate complex. Using the water-soluble Rice Bran (RB) as a control, a cross over double-blind study was conducted on both substances over a 6-week administration period. Fifty elderly people aged from 70 to 95 years participated in the study and the comparative data from 36 participants were analyzed. There were no withdrawals from in the study due to the side effects of the experimental foods. Symptoms were observed and scored. The total symptom score for the RB treatment group was three times higher than that for the HRB treatment group. The average duration of symptoms was 2.6 days for RB whereas it was only 1.2 days for HRB. Furthermore, some immunomodulatory action was observed in laboratory tests. HRB was shown to be useful in reducing the physical stress associated with acute respiratory tract infection.
2005

Hyrolyzed rice bran reduces the aggravation of protein metabolism in streptozotocin-induced diabetic rats

Presenters: Kitamura N., Ohara I., (Aichi Gakusen University) and Maeda H. (Daiwa Pharmaceutical)
Event: 45th Annual Meeting of the American College of Nutrition in California.

2004

Chemical structure of immunostimulating substances from rice bran

Presenters: Miura T., Chiba M., Miyazaki Y., Kato Y. (Hirosaki University) and Maeda H. (Daiwa Pharmaceutical)
Events: 2004 Annual Meeting of the Japanese Society of Applied Glycoscience and the 12th Symposium on Amylases and Related Enzymes, Kagoshima.

2004

Augmentation of Macrophage Phagocytosis by Modified Arabinoxylan from Rice Bran (BioBran/MGN-3)

Authors: M. Ghoneum, M. Matsuura
Journal: International Journal of Immnopathology and Pharmacology, Vol.17,No.3, pp.283-292

abstract
Abstract:MGN-3/Biobran, modified arabinoxylan rice bran, has been shown to be a potent biological response modifier (BRM) as manifested by stimulation of different arms of the immune system such as NK, T and B cells; however, its effect on macrophages has not yet been studied. The effects of MGN-3 on macrophage function was examined in vitro using 3 models: human macrophage cell line U937, murine macrophage cell line RAW264.7, and murine peritoneal macrophages (P-Mf). Treatment with MGN-3 resulted in an increase in the percentages of attachment and phagocytosis of yeast by macrophages. The effect depends on the type of macrophage and the dose of MGN-3 applied. Macrophages also demonstrated enhancement in their spreading ability, post treatment with MGN-3. Results also showed that MGN-3, in a dose-dependent manner (1, 10,100 µg/ml), significantly induced high levels of production of cytokines: TNF-a and IL-6. In addition, MGN-3 significantly increased nitric oxide (NO) production. This data demonstrates that MGN-3 is a potent inducer of phagocytic function by macrophage, and may suggest that MGN-3 is a useful agent for fighting microbial infection.
2004

Evaluation of the effect of hyrolyzed rice bran on reducing respiratory symptoms in smokers

Authors: Kudo M., Maeda H. (Daiwa) and Nakamichi N. (Jikei University, N.S. Clinic) at the 21st Symposium of Medical and Pharmaceutical Society for Wakan-Yaku.

2004

A Case Where an Immunomodulatory Food was Effective in Conservative Therapy for Progressive Terminal Pancreatic Cancer

Authors: Kazutoshi Kaketani, Hanzomon Gastrointestinal Clinic
Journal: Clinical Pharmacology and Therapy Vol. 14/No.3

abstract
Abstract:A patient with terminal pancreatic cancer accompanied by distant metastasis who was unfit for radical surgical treatment was subjected to treatment with the rice bran arabinoxylan derivative, which is reported to have biological defense action, and it water, which can enhance blood circulation and transportation of nutrients and drugs (Vehicle action), in addition to low toxic chemotherapeutic agents in order to maintain biological functions and QOL. As a result, satisfactory therapeutic effects were obtained, such as improvements in biological functions and spontaneous cure power.
2004

Effect of Long-term Administration of Immunomodulatory Food on Cancer Patients Completing Conventional Treatments

Authors: Hiroshi Tsunekawa, Tsunekawa Gastrointestinal Clinic, published in
Journal: Clinical Pharmacology and Therapy Vol. 14/No.3

abstract
“Abstract:A study was conducted to investigate the effects of long-term administration of the immunomodulatory food BioBran, rice bran arabinoxylan derivative, on 16 cancer patients, mainly in stage IV with various conventional lesions, who had just undergone conventional cancer treatments, such as surgery, chemotherapy and radiotherapy. The main clinical observations were the safety and eifect of BioBran on the nutritional state of the patients, who were exhausted due to treatment. During the administration period, no decreases in body weight and leukocyte count or significant changes in leukogram were observed. Rather, the leukocyte count increased. ln addition, most patients showed an increase in NK cell activity and a remarkable decrease in tumor markers.
2004

The Life Prolongation and QOL Improvement Effect of Rice Bran Arabinoxylan Derivative (MGN-3, Biobran) for Progressive Cancer

Authors: Kihachiro Takahara and Kamataro Sano, Sano Surgery Clinic

Journal: Clinical Pharmacology and Therapy Vol. 14/No.3

abstract
“Abstract: The present study was designed to determine whether or not the administration of MGN-3 could have its apothanasia effect and improve the QOL for 205 progressive and partially nretastasized cancer patients in late III—IV stages after surgery. MGN-3 is a rice bran arabinoxylan derivative and known to have immtmomodulation activity. The participants in this clinical study are hospitalized patients in our clinic treated with complementary alternative medicines (we call it “Non-Conventional Therapy”) and anticancer medicines with lesser side effects. The 205 patients hospitalized for 6 months were grouped into two groups, viz, 109 patients (control group) treated with our standard complementary alternative medicines, and 96 patients who were further given MGN-3 (MGN-3 group) for one year and a half.
All the patients were measured for natural killer activity as an indication for the variation of immunoparameters. Simultaneously, the QOL of the patients was also checked. The NK cell activities ofthe patients alter surgery were low on average; however, by the administration of MGN-3, NK activity was observed to increase and the apothanasia ratio also increased; the higher the patient NK activity is, the higher the apothanasia ratio was observed to rise. The above Endings indicate that NK activity can be used as a pathological index of progressive cancers. QOL improvement was also observed with the administration of MGN-3.”
2004

One Case of a Patient with Umbilical Metastasis of Recurrental Cancer (Sister Mary Joseph’s Nodule, SMJN) Who has Survived for a Long Time under Immunomodulatory Supplement Therapy

Authors: Tomonori Kawai, Shinkurashiki icho komon geka
Journal: Clinical Pharmacology and Therapy Vol. 14/No.3

abstract
Abstract: A 64—year-old female patient with umbilical metastasis of recurrent colorectal cancer (SMJN) was subjected to complementary medicine using the rice bran arabinoxylan derivative), a food component of BRM activity in addition to chemotherapy in order to maintain the QOL and prolong life. Although the umbilical metastasis is tending to grow, the patient is in a good nutritional condition and has survived for more than two years from diagnosis. SMJN is a distant metastasis, and even if it is the first occurrence, radical treatment may not be possible in most cases. This case suggests that the maintenance of the QOL and physiological function may lead to a prolongation of life even in patients with terminal cancer with extremely poor prognosis like this. And this case presents the benefit of supplementary therapy using functional foods.
2004

The Clinical Significance of Biobran in the Immunotherapy for Cancer

Authors: Yasushi Okamura, Director of the Insitute of Life Science, Japan
Journal: Clinical Pharmacology and Therapy Vol. 14/No.3

abstract
“Abstract: The clinical treatments for cancer were (1) surgery, (2) radiotherapy, and (3) chemotherapy with anticancer drugs. For surgery, even if the procedure used is highly sophisticated, cancer cells may be transported to other organs via the vascular or lymph system. For radiotherapy, although it destroys cancer tissues it may also damage the surrounding functioning tissues. Anticancer drugs may destroy cancer cells as well as normally functioning cells of other organs.
Consequently, these drawbacks of the three types of treatments must be recognized when addressing cancer patients. This is where immunotherapy counts. The author has been working with immunotherapy for 25 years, and this time chose combination therapy with BioBran (rice bran arabinoxylan derivative), and BRP (Bio-Reproducing Protein) intravenously.
Case 1. K. M. 67-year-old, M. Liver cancer with intestinal metastasis
Case 2. M. O. 65—year-old, M. Liver cancer
Case 3. F. M. 71—year-old, F . Liver cancer
Case 4. H. H. 76-year-old, F . Lung cancer
Case 5. T. O. 58-year-old, M. Colorectal cancer with liver metastasis
Above five cases, blood samples were taken once a month to measure tumor markers and immunopotency, and the results were compared with the change in clinical conditions. As a result, improvements were noted in all the cases.”
2004

Modified arabinoxylan rice bran (MGN-3 /Biobran) potentiates apoptosis in cancer cells induced by multiple anti-cancer agents in vitro

Authors: Ghoneum M. and Gollapudi S.
Event: 7th International Symposium on Predictive Oncology & intervention Strategies in Nice.

2003

Effect of rice bran arabinoxylan and shark lipid extract on complementary and alternative therapy

Presenter: Omori T. (Ginza San Espero Omori Clinic)
Event: 7th Conference of the Japanese Assoc. for Alternative, Complementary and Traditional Medicine (JACT) at Kobe.

2003

The effect in the physiological function of a modified arabinoxylan rice bran

Authors:Masada M., Maeda H. and Tazawa K., Chiba University, Daiwa Pharmaceutical Co. Ltd., Toyama Medical University.
Event: Japan Society for Biological Therapy

2003

The oral administration of the hydrolysis rice bran prevents a common cold syndrom for elderly perople based on immunomodulatory function

Presenters: Maeda H., Omura K. and Zhu K., Daiwa Pharmaceutical Co. Ltd.
Event: Medical and Pharmaceutical Society, Wakan Yaku

2003

Modified arabinoxylan rice bran (MGN-3 /Biobran) sensitizes human T cell leukemia cells to death receptor (CD95)-induced apoptosis

Authors: Mamdooh Ghoneum and Sastry Gollapudi
Journal: Cancer Letters 201 (2003) 41-49 / Elsevier.

abstract
Abstract: MGN-3, an arabinoxylan extracted from rice bran that is treated enzymatically with an extract from Shiitaki mushrooms, is an effective biological response modifier that increases NK cell activity, and potentiates the activity of conventional chemotherapeutic agents. In this study, we investigated the effect of MGN-3 on death receptor-induced apoptosis in the human leukemic HUT 78 cell line. HUT 78 cells were pre-treated with MGN-3, and then were incubated with the agonistic antibody against death receptor (Fas, CD95). Apoptosis was determined by the propidium iodide technique using FACScan. Activation of caspase 3, caspase 8, and caspase 9 was determined by flow cytometry. Mitochondrial membrane potential was measured with DIOC6 dye using FACScan. Expression of CD95 and Bcl-2 were measured by iiow cytometry. In a dose-dependent manner, MGN-3 enhanced anti-CD95 antibody-induced apoptosis. Increased cell death was correlated with increased depolarization of mitochondrial membrane potential and increased activation of caspase 3, caspase 8, and caspase 9. MGN-3 treatment had no effect on the level of expression of CD95, but it caused down regulation of Bcl-2 expression. These results suggest that MGN -3 increases the susceptibility of cancer cells to undergo apoptosis mediated by death ligands, which may be relevant for anti—cancer activities.
2003

Immunoactivation therapy for various prograssive cancers using rice bran arabinoxylan derivative (Biobran)

Presenters: Tsunekawa H. and Maeda H.
Event: The Japanese Society for Complementary and Alternative Medicine

2003

A novel approach to breast cancer therapy: modified arabinoxylan rice bran (MGN-3/Biobran) enhances apoptosis of human breast cancer cells following phagocytosis of saccharomyces cerevisiae, the baker’s yest, invitro

Presenters: Ghoneum M. (UCLA) and Gollapudi S. (University of California Irvine)
Event: The Japanese Society for Complementary and Alternative Medicine,Sendai American Association for Cancer Research Speicial Conference in California.

2003

Effect of Biobran proved by Scientific Studies

Presenter: Maeda H., Daiwa Pharmaceutical Co. Ltd.
Event: Japanese Academy for Clinical Complementary & Alternative Medicine

2003

Oral administration of Hydrolysed Rice Bran prevents common cold syndrome in the elderly based on immunomodulatory function

Presenters: Omura K. (Dokkyo University School of Medicine), Ichihashi K. (Ichihashi Clinic), Maeda H. (Daiwa Pharmaceutical) and Tazawa K. (Toyama Medical and Pharmaceutical University) at the Event: 4th Conference of the Japanese Society of Anti-Aging Medicine in Tokyo.

abstract
Abstract: The preventive effect of RIBEX against the common cold syndrome was examined on elderly people. RIBEX, containing arabinoxylan derivatives Hydrolysis Rice Bran (HRB), was prepared from the water soluble dietary fiber fraction from rice bran through partial processing by carbohydrate complex of Lentinus Edodes mycelia (shiitake). Using the non-chemical and non-biological treated water soluble fraction of Rice Bran (RB) as control, the examination was conducted by the cross-over double blind manner through the administration term of 6 weeks for each material. Fifty elderly people who stayed in a care institution under Japan’s Long-term Care Insurance participated in this study. The results of thirty-six participants who showed comparative data in both terms were analyzed statistically. The most popular reason for withdrawal from the study was “leaving from the institution by a care contract”. There was no withdrawal due to the side effects of test foods. We observed symptoms such as “cough”, “fatigue”, “fever”, “sore throat”, “sputum”, “nasal signs”, and “sore breast”, and calculated them, based on the judgments of the medical staff. Although thirteen participants (36.1%) experienced at least one symptom in the both terms, the total scores were of significantly high value (p<0.05) in the term of R.B. The average duration in which the participants experienced symptoms was 2.6 days in the term of RB whereas 1.2 days in that of HRB, which was not statistically significant. While there are many reports that HRB increases NK cell activity, no significant data was observed in this study because the participants had enough NK cell activities from the start.
HRB shortened the duration of the symptoms, reduced the worse and the necessity of symptomatic therapy, and was useful for the reduction of physical burden of acute respiratory tract infection.”
2003

Modified Arabinoxylan from Rice Bran (Biobran/MGN-3) Beneficial for Weight Loss of Mice as a Major and Acute Adverse Effect of Cisplatin

Authors: Yuzo Endo and Hiroshi Kanbayashi from McMaster University in Ontario
Journal: Pharmacology & Toxicity, Vol. 92, pp.300-303, 2003

abstract
Abstract: Alkylating agents and antimetabolites remain prominent in a wide variety of cancer chemotherapy protocols on the basis of more selective effects on the faster than normal mitotic cycles of malignant cells. Among new platinum—containing anticancer molecules, the lead compound cisplatin (Cis-platinum (II) diammine dichloride) has been known to possess beneficial anticancer properties in terms of specific interaction of cisplatin and DNA strands. Cisplatin (Rosenberg ez al. 1969) has been encouraged for treatment of head and neck, bladder, and cervical cancers (Loehrer & Einhorn 1984), as well as breast cancer (Smith & Talbot 1992). Although the prevalent incidence of lung, gastric, breast, colorectal and prostate cancers place them in top ranks of the most common cancers in the civilized countries, many of these advanced cancers are unresponsive to chemotherapy. Platinum-based drugs would be a potent choice in these situations, but they frequently cause substantial side effects, such as nausea, vomiting, nephropathy and hypomagnesaemia due to damage of renal tubules (Lajer & Daugaard 1999). Furthermore, in addition to hearing loss and peripheral neuropathy, myelosuppression is one of the most devastating suppressive side-effects (Prestayko et al. 1979) leading to immunocompromized states. Therefore, any reduction of the side effects of cisplatin would be valuable.
2002

Evaluation of the effects of asthma prevention and symptom reduction by enzymatically modified rice-bran foods in asthmatic model mice

Presenters: Kanbayashi H. and Endo Y., Department of Pathological Molecular Medicine, McMaster University
Event: 52nd Conference of Japanese Society of Allergology, Jokohama, Japan

2002

Effect of enzyme-processed rice bran hemicellulose (MGN-3) on experimental liver dysfunction in rats

Presenters: Yamada T., Daizou A., Poindoglun K., Egashira K., Maeda H. and Sanada H. Graduate School of Science and Technology, Chiba University, Department of Bioresources Chemistry, Chiba University and Daiwa Pharmaceutical Co. Ltd.
Event: Presented at the 7th Conference of Japanese Association for Dietary Fiber Research, Tokyo, Japan

2002

A basic study on protective effects of Biobran against myelogenetic death by radiation exposure

Presenter: Dr. S. Nakatugawa of Nagoya University Medical School Hospital in Japan
Event: American Association for Cancer Research meeting in Boston, MA.

2002

MGN-3 potentiates death receptor-induced apoptosis in cancer cells Presenters: M. Ghoneum and S. Gollapudi, Drew University of Medicine and Science, Los Angeles, CA, UC Irvine, Division of Basic and Clinical Immunology, Irvine CA

Event: 93rd Annual Meeting 2003 of American Association for Cancer Research, Boston, USA

2002

Normalization of the lymphocyte system in peripheric blood reaction by arabinoxylan from rice bran (MGN-3)

Presenters: Ueda Y., Masada M. and H. Maeda. Department of Bioresources Chemistry, Faculty of Horticulature, Chiba University and Daiwa Pharmaceutical Co. Ltd.
Event: Presented at the 43rd Annual Meeting at the American Clooege of Nutrition, San Antonio, Texas

2002

Effects of rice bran arabinoxylan on induced hepatitis in rats Author: Maeda H. et al.

Journal: Journal of Japanese Association for Dietary Fiber Research (Vol 6, No2)

2002

Effects of modified rice-bran arabinoxylan on NK activity of human peripheral blood lymphocytes

Presenters: Shimomura C., Ueda Y., Kodama H., Maeda H. and M. Masada, Department of Bioresources Chemistry, Faculty of Horticulture, Chiba University and Daiwa Pharmaceutical Co., Ltd.
Event: Paper presented at the 46th Japan Society for Bioscience,Biotechnology and Agrochemistry, Sendai, Japan

2002

Study on the growth inhibiting component of cancerous cells in culture cell lines derived from modified rice-bran arabinoxylan

Presenters: Miyazaki F., Hashizume T., Kodama H., Maeda H. and M. Masada.Technology Department, Kazami Co., Ltd.,Department of Biresources Chemistry, Faculty of Horticulautre, Chiba University and Daiwa Pharmaceutical Co., Ltd.
Event: 46th Japan Society for Bioscience, Biotechnology and Agrochemistry

2002

Modified Rice Bran Improves Glucose Tolerance in NIDDM Adult Rats Given Streptozotocin as Neonates

Authors: Ohara, K. Onai and H. Maeda

abstract
Abstract: The effect of modified rice bran on glucose tolerance was studied in adult non-insulin dependent diabetes mellitus (NIDDM) rats that had been caused by intraperitoneal injection of 100 mg per kg streptozotocin (STZ) at 1. 5 days of age. Following weaning, the animals were divided into 3 groups, 5 control rats fed a 1.7% cellulose diet, 7 diabetic rats fed a 1. 7% cellulose diet and 8 diabetic rats fed a 1% modified rice bran (+0. 7% cellulose) diet. Rats had free access to one of experimental diets and water for 60 days. Oral glucose tolerance tests were performed at 8 weeks of age. Trunk blood was collected and plasma levels of insulin, glucose, triglycerides, total cholesterol, HDL-cholesterol, total protein, albumin and urea nitrogen were measured. Plasma glucose levels in diabetic rats fed the 1.7% cellulose diet increased significantly faster and to higher levels than those of the normal control in an oral glucose tolerance test. In the NIDDM rats fed the modified rice bran diets, the rapid rise of plasma glucose levels was depressed. Among the various other biochemical measurements only the plasma total cholesterol levels were significantly reduced by the administration of modified rice bran. Modified rice bran holds promise as a dietary fiber supplement for the treatment of diabetes.
2001

A Descriptive Questionnaire-Based Study on the Use of Biobran (MGN-3) in Chronic Fatigue Syndrome

Author: Dr. J. Kenyon
Journal: Townsend Letter, November 2001.

2001

Inhibitory effect of MGN-3 on the progress of atopic dermatitis in NC mice Presenters: S. Nonoyama and L. Lin

Event: 11th International Congress of Immunology and written up in the Scandinavian Journal of Immunology — Volume 54, Supplement 1, July /August 2001.

2001

MGN-3, a novel antitumor agent

Presenters: K. Uyemura, K. Tachiki, M. Ghoneum, T. Makinodan, N. Makhijani and D. Yamaguchi
Event: 92nd Annual Meeting, American Association for Cancer Research. The research team found that MGN-3 not only increased NK cell activity, but also the production and secretion of cytokines such as IL-10 and IL-12 by cancer cells such as MCF-7. Treatment of cultures of MCF-7 cells with MGN-3 also can arrest cell growth.

2001

Application of the alterantive medicine of a new physiological active substance “arabinoxylan derivative” (MGN-3, Biobran)

Presenters: Maeda H., Daiwa Pharmaceutical Co. Ltd.
Event: 7th Conference of Japan Mibyou System Association, Nagoya, Japan

2001

The basic study of arabinoxylan compound (MGN-3) on the activation of vital defence

Authors: N. Sudo, K. Tatoe, N. Koyama, H. Kanna, K. Hirayama, and C. Kubo

abstract
Abstract: Arabinoxylan (hereafter called MGN-3) is a plant polysaccharide processed food with a biophylactic action, which mainly contains polysaccharides such as hemicellulose and arabinoxylan and glycoprotein. MGN-3 is known to have various biophylactic actions such as in vitro NK cell activity stimulation and anti-HIV effect. In the present study, the vital defense activating effect of MGN-3 was studied in 3 animal experiments: Experiment 1 examined its effect on the survival in a lipopolysaccharide-induced lethal sepsis model, Experiment 2 studied the anti-stress effect on restraint stress, and Experiment 3 examined its effect on the survival of autoimmune disease-prone (NZB x NZW) F1 mice.
2001

The Effect of Modified Arabinoxylan from Rice Bran (Biobran/MGN-3) on Cisplatin and Doxorubicin Induced Toxity in the Rat

Authors: Jacoby, Wnorowski, Sakata and Maeda
Journal: Journal of Neutraceuticals, Function & Medical Foods, Vol.3 (4), pp.3-11, 2001.(MGN-3 protects rates given an acutely toxic dose of cisplatin or adriamcyin. This indicates that the MGN-3 may well be good at improving the quality of life in patients receiving chemotherapy and may be a useful adjunct, therefore, to cancer chemotherapy.)

abstract
Abstract: MGN-3 (BioBran) is derived from rice bran and is produced by the partial hydrolysis of the water soluble hemicellulose fraction of rice bran by carbohydrases derived from Lentius eclarles mycelia.It is a biological response modifier producing an increase in natural killer cell activity in immunocompromised patient. The aim ofthe study was to evaluate orally administered MGN-3 against gross pathological changes and weight loss produced by a single intraperitoneal dose of cisplatin or doxorubicin by daily oral dosing of 5 or 50 mg/kg MGN-3. Male Sprague-Dawley rats received either vehicle or MGN-3 prior to and after a single dose of cis-platinum or doxorubicin. Rats were observed for clinical signs daily for 11 days and body weights were recorded every other day. All animals were euthanized and necropsied on Day 11. Lethality was observed only in rats receiving cisplatin (50% with cisplatin alone reduced to 10% in rats receiving MGN-3 5 mg/kg, and 40% after MGN-3 50 mg/kg). Rats receiving MGN-3 at 5 or 50 mg plus cis-platinum or doxorubicin had a statistically significant greater weight gain than that observed with the chemotherapeutic agent alone. Rats receiving MGN-3 appeared healthier; gained weight and had a lower incidence of diarrhea and gross intestinal pathology. MGN-3 was effective at maintaining body weight after a toxic dose ofeither chemotherapeutic agent and protected against gross gastrointestinal pathological changes and diarrhea. MGN-3 may have potential for improving “quality of life” of patients receiving chemotherapy.
2000

Natural biological response modifier (MGN-3) shown to be effective against tumor cell growth

Presenters: M. Ghoneum, K. Tachiki, K. Ueyama, T. Makinodan, N. Makhijani and D. Yamaguchi
Event: 8th International Congress on Anti-Aging & Biomedical Technologies, December 14-17, 2000, Las Vegas, NV.

2000

Evaluation of immune (arabinoxylan) therapy seen from NK cell activity and the CD4/CD8 ration on cancer patients

Event: The 3rd Annual Meeting of the Japanese Society for Complementary & Alternative Medicine & Treatment, Tokyo, Japan.

2000

Inhibitory effects of MGN-3 (modified Arabinoxylan from rice bran) on free radical

Presenters: T. Saito, H. Ohkami, K. Tsukada, K. Tazawa, H. Namikawa, S.Oida, J. Koike, M. Yatsuzuka, M. Masada, and H. Maeda
Event: 59th Annual Meeting of the Japanese Cancer Association, Yokohama Japan. Toyama Medical University, Chiba University and Daiwa Pharmaceutical.

2000

The Effect of MGN-3 on cisplatin and adriamycin induced toxicity in the rat

Authors: Jacoby, Wnorowski, Sakata and Maeda
Journal: American Society for Pharmacology and Experimental Therapeutics,Boston, USA.
(MGN-3 protects rates given an acutely toxic dose of cisplatin or adriamcyin.This indicates that the MGN-3 may well be good at improving the quality of life in patients receiving chemotherapy and may be a useful adjunct, therefore, to cancer chemotherapy.)

2000

Effects of modified rice bran on serum lipids and taste preference in streptozotocin-induced diabetic rats

Authors: Ohara, Agr, Tabuchi, Onai and Econ from Kobe Women’s University in Kobe Japan
Journal: Journal Of Nutritional Research, Vol. 20, No. 1, pp.59-68, 2000
(The study was to determine whether the administration of MGN-3 could improve streptozotocin-induced diabetes. Results: serum triglycerides and total cholesterol decreased, and polyuria and taste was improved.)

abstract
Abstract: The present study was designed to determine whether or not the administration of modified rice bran could improve streptozotocin (STZ)-induced diabetes. Taste preferences were also compared in diabetic and control rats. Male Sprague-Dawley rats were divided into control and diabetic groups. A single STZ injection, 65 mg per kg body mass i.p., induced diabetes. Rats were given free access to commercial diet and water for 2 months and modified rice bran (0.5 g per kg body mass) was administered daily by stomach tube. Two-bottle-choice preference tests between aqueous solutions of either 5 mM citric acid, 27 mM monosodium glutamate, 0.016 mM quinine, or 0.82 mM saccharin in deionized water were conducted in the experimental period. Blood was collected and serum levels of glucose, insulin, triglycerides, total cholesterol, HDL-cholesterol, urea nitrogen, total protein, albumin, and zinc were measured. Serum triglycerides and total cholesterol decreased with the administration of modified rice bran, although serum insulin and glucose remained low and high, respectively. Water intake was also reduced by the modified rice bran, which suggests that polyuria induced by STZ improved. Diabetic rats showed significant aversion to citric acid and quinine when compared with control rats. Modified rice bran can be useful as a dietary fiber supplement for the treatment of diabetes. In addition, high taste sensitivity for sourness and/or bitterness is a characteristic of STZ-induced diabetes.
2000

Production of Tumor Necrosis Factor-α and Interferon-γ from Human Peripheral Blood Lymphocytes by a Modified Arabinoxylan from Rice Bran (Biobran/MGN-3), and Its Synergy with Interleukin-2 In Vitro

Authors: Ghoneum and Jewett
Journal: Cancer Detection and Prevention, 24 (4): 314-324 (2000).
(This study showed that MGN-3 is a potent TNF-a producer and that it induces the TNF-a secretion in a dose dependent manner. Also, a combination of MGN-3 and IL-2 resulted in a synergistic induction of TNF-a and IFN-g secretion.MGN-3 appears to increase the expression of CD69 activation antigen.)

abstract
Abstract: Recently, we presented evidence for the role of MGN-3, an enzymatically modified arabinoxylan extracted from rice bran, in potent activation of human natural killer (NK) cell function in vivo and in vitro. In the current study, we examined the mechanism by which MGN-3 elevated NK cytotoxic activity. We did this by testing the action of MGN-3 on the levels of both tumor necrosis factor-a (TNF-a) and interferon-? (IFN-?) secretions and MGN-3 function on the expression of key cell surface receptors. Peripheral blood lymphocytes were treated with MGN-3 at concentrations of 0.1 mg/ml and 1 mg/ml, and supematants were subjected to enzyme-linked immunosorbent assay. Results showed that MGN-3 is a potent TNF-a inducer. The effect was dose-depen-dent. MGN -3 concentration at 0.1 and l mg/ml increased TNF-a production by 22.8- and 47.1-fold, respectively. MGN-3 also increased production of IFN-? but at lower levels as compared to TNF-a. With respect to key cell surface receptors, MGN-3 increases the expression of CD69, an early activation antigen at 16 hours after treatment, Furthermore, the interleukin-2 receptor CD25 and the adhesion molecule ICAM-1 (CD54) were upregulated after treatment with MGN -3. Treating highly purified NK cells with MGN-3 also resulted in increased levels of TNF-a and IFN-? secretion in conjunction with augmentation of NK cell cytotoxic function. Furthermore, addition of MGN-3 to interleukin-2-activated NK cells resulted in a synergistic induction of TNF-a and IFN-? secretion. Overall, our data suggest that MGN-3, a novel biological response modifier, can be used as a safe alternative or as an adjuvant to the existing immunotherapeutic modalities.
2000

Physiological Activator, Oryza Sativa L. Arabinoxylan Derivative (MGN-3)

Presenter: H. Maeda
Event: 6th Japanese Congress on Mibyo System, Hiroshima Japan. Daiwa Pharmaceutical Co. Ltd.

2000

Scavenging Activity of Modified Arabinoxylan from Rice Bran (Biobran/MGN-3) with Natural Killer Cell Activity on Free Radicals

Presenters: K. Tazawa, H. Namikawa, S. Oida, K. Ito, M. Yatsuzuka, J. Koike, M. Masada and H. Maeda
Event: 12th Japanese Conference on Bio Therapy, Yokohama Japan. Toyama Medical University, Chiba University and Daiwa Pharmaceutical.

abstract
Abstract: MGN-3, which produces a remarkable increase in natural killer cell activity, showed a high scavenging rate on hypoxanthine-xanthine oxidase generated superoxide anion radicals, and on ferrous sulfate-hydrogen peroxide and UV light reaction system generated hydroxyl radicals. The S-group of MGN-3 fractions (L>10,000 molecular, 10.000>M>3.000 molecular and 3.000 molecular>S) showed the highest scavenging rate on superoxide anion radicals and the UV light reaction system. There was no difference in the scavenging rate for hydroxyl radicals by the Fenton reaction.
1999

One Sizeable Step for Immunology, One Giant Leap for Cancer Patients

Author: M. Ghoneum
Journal: Townsent Letter / January 2000 / #198

abstract
Abstract:
1999

Immunostimulation and Cancer Prevention

Presenter: M. Ghoneum
Event: 7th International Congress on Anti-Aging & Biomedical Technologies,Las Vegas, USA. Drew University.

1999

Application of modified rice bran dietary fiber to diabetes and taste preference in streptozotocin-included diabetic rats

Presenters: I. Ohara, K. Onai and H. Maeda
Event: 2nd International Conference on Food Factors, Kyoto, Japan. Laboratory of Nutrition, Kobe Women’s University, and Daiwa Pharmaceutical.

1999

Modified rice bran improves glucose tolerance in NIDDM adult rats given streptozocin as neonates

Presenters: Ohara I., Onai K. (Kobe Women’s University) and Maeda H.(Daiwa)
Event:40th meeting of the American College of Nutrition in Washington DC.

1999

Evaluation of MGN-3 (Biobran) on superoxide scavenging activity Presenters: K. Tazawa, H. Namikawa, S. Oida, K. Ito, M. Yatsuzuka, J. Koike, H. Maeda

Event: 6th Japanese Conference on Cancer Prevention, Tokyo Japan. Toyama Medical University.

1999

A case study of supplementary application of rice bran Arabinoxylan (MGN-3) to bone metastasis from lung cancer

Presenters: T. Sobajima and H. Maeda
Event: 2nd Conference of Japanese Association for Alternative,Complementary and Traditional Medicine (JACT), Tokyo Japan. Sobajima T.,Hoshigaoka Welfare Annuity Hospital and Maeda H., Daiwa Pharmaceutical Co.Ltd., Tokyo.

1999

NK immunorestoration of cancer patients by MGN-3, a modified arabinoxylan rice bran (study of 32 patients up to 4 years)

Author: M. Ghoneum
Event: 6th International Congress on Anti-Aging & Bio-Medical Technologies and published in Anti-Aging Medical Therapeutics, Vol.3.(MGN-3 is a potent biological response modifier in its ability to significantly increasing the activity of NK cells in both animals and humans. The mechanism by which it does this is firstly that it increases the granularity of the NK cells andsecondly it elevates cytokine production.)

abstract
Abstract: NK cells have been characterized as non-B cells or non-T cells lacking the characteristics of mature macrophages which develop from the bone marrow independently of thymic influence. NK cells play a crucial role in tumor rejection, immune surveillance, resistance to infections, and immune regulation. NK cell destruction of cancer cells involves a sequence of events. First, the NK cell recognizes and binds to the cancer cell. This process requires receptor-to-receptor interaction. Next, the NK cell releases granules which penetrate the cancer cell and ultimately kill it. The NK cell is then free to bind to another cancer cell and repeat the same process. However, cancer cells know how to fight back in a sort of cell war. We found for the first time in our laboratory that cancer cells can destroy WBCs through the phenomenon of phagocytosis. We have observed three ways in which this is done. The cancer cell can extend two arms around the WBC or it can develop a cup-shaped opening where the WBC is drawn inside. A third way is for the cancer cell to extend a long arm to capture the WBC and finally draw it inside the cancer cell where it is digested. In addition, extensive work by others has shown that cancer cells secrete immune-suppressive substances which inhibit the function of the immune system. Many attempts have been made in the last 25 years to strengthen the power of the immune system using different biological response modifiers (BRMs). These are substances originating from bacteria and fungi which possess immunoaugmentory properties. In addition, some kinds of cytokines serve as BRMS such as interferons, interleukin-2 and interleukin-12. There are two problems associated with these BRMS: 1st) toxicity and 2nd) the development of hyporesponsiveness in which a single administration of the BRM can significantly enhance NK cell activity, but that repeated administration of the same BRM results in depression of NK cell activity. It is interesting to note that MGN-3 has advantages over other BRMs. It is nontoxic and has not shown hyporesponsiveness in the four years that the patients have been followed. This work was undertaken in order to investigate the augmentory effect of a new BRM known as MGN-3 on NK cell function and T and B cell proliferation in 32 patients. Tumor-associated antigens were reported for selected patients.
1999

Active oxygen radical scavenging activity of the plant polysaccharide processed foodstuff Biobran

Presenter: K. Tazawa, Toyama Medical and Pharmaceutical University, and H.Maeda, Daiwa Pharmaceutical Co. Ltd.
Event: 3rd JsoFF Conference.

1999

Immunopotentiation by utilization of MGN-3 tissue

Presenter: M. Ghoneum
Event: Congress on Anti-Aging Medicine in Nevada.

1999

NK cell activity by MGN-3

Presenter: M. Ghoneum
Event: 26th Academy of Alternative Medicine of Cancer in Los Angeles.

1999

Synergistic effect of modified arabinosylan (MGN-3) and low dose of recombinant IL-2 human NK cell activity and TNF-α production

Presenters: M. Ghoneum and A. Jewett
Event: Conference of Anti-Aging Mechanism run by the American Academy of Anti-Aging Medicine in NJ

1998

MGN-3 immunotherapy for the treatment of cancer

Presenter: M. Ghoneum
Event: First International Symposium on Disease Prevention by IP6 and Other Rice Components in Japan. (The 10 cancer patients in the study showed large increases in NK cell activity and elevated T and B cell function by its ability to produce cytokines such as TNF-α and IFN-γ.)

1998

Enhancement of human natural killer cell activity by modified arabinoxylan from rice bran (MGN-3)

Author: M. Ghoneum
Journal: International Journal of Immunotherapy XIV (2) 89-99 (1998) (Study involved 24 individuals taking MGN-3 at 3 different concentrations. NK cell activity was significantly increased after 1 week and peaked at 2 months. Also measured was a significant increase in interferon-γ.)

abstract
Abstract: Arabinoxylane from rice bran (MGN-3) was examined for its augmentory effect on human NK (NK) cell activity in vivo and in vitro. Twenty-four individuals were given MGN-3 orally at three different concentrations: 15, 30 and 45 mg/kg/day for 2 months. Peripheral blood lymphocyte—NK cell activity was tested by Cr release assay against K562 and Raji tumor cells at 1 week, 1 month and 2 months post-treatment and results were compared with baseline NK activity Treatment with MGN-3 enhanced NK activity against K562 tumor cells at all concentrations used. ln a dose-dependent manner MGN-3 at 15 mg/kg/day increased NK activity after 1 month posttreatment (twofold over control value), while significant induction of NK activity at 30 mg/kg/day was detected as early as 1 week posttreatment (three times control value). NK cell activity continued to increase with continuation of treatment and peaked (fivefold) at 2 months (end of treatment period). Increasing the concentration to 45 mg/kg/day showed similar trends in NK activity however the magnitude in values was higher than for 30 mg/kg/day After discontinuation of treatment, NK activity declined and returned to baseline value (14 lytic units) at 1 month. Enhanced NK activity was associated with an increase in the cytotoxic reactivity against the resistant Haji cell line. MGN-3 at 45 mg/kg/day showed a significant increase in NK activity after 1 week (eightfold) and peaked at 2 months posttreatment (27 times that of baseline). Culture of peripheral blood lymphocytes (PBL) with MGN-3 for 16 h demonstrated a 1.3 to 1.5 times increase in NK activity over control value. The mechanism by which MGN-3 increases NK activity was examined and showed no change in cluster of differentiation (CD) 16+ and CD56+ CD3¯ of MGN-3-activated NK cells as compared with baseline value; a fourfold increase in the binding capacity of NK to tumor cell targets as compared with baseline value; and a significant increase in the production of interferon-? (340-580 pg/ml) postculture of PBL with MGN-3 at concentrations of 25-100 µg/ml. Thus, MGN-3 seems to act as a potent immunomodulator causing augmentation of NK cell activity and with the absence of notable side-effects, MGN-3 could be used as a new biological response modifier (BRM) having possible therapeutic effects against cancer.
1998

Anti-HIV activity in vitro of MGN-3, an activated arabinoxylan from rice bran

Author: M. Ghoneum
Journal: Biochemical and Biophysical Research Communications Journal 243, 25-29 (1998), Article No. RC978047. (This is a detailed write up of the abstract Ghoneum presented in July 1996 at the International Conference on AIDS in Vancouver.)

abstract
Abstract: MGN-3, an arabinoxylane from rice bran that has been enzymatically modified with extract from Hyphomycetes mycelia, was tested for anti-HIV activity in vitro. MGN-3 activity against HIV -1 (SF strain) was examined in primary cultures of peripheral blood mononuclear cells. MGN-3 inhibited HIV-1 replication by: (1) inhibition of HIV-1 p24 antigen production in a dose dependent manner-MGN-3 at concentrations of 12.5, 25, 50, and 100 µg/ml showed 18.3, 42.8, 59, and 75% reduction in p24 antigen, respectively; and (2) inhibition of syncytia formation maximized (75%) at concentrations of 100 µg/ml. Further studies showed that ingestion of MGN-3 at concentration of 15 mg/kg/day resulted in a significant increase in T and B cell mitogen response at 2 months after treatment: 146% for PHA, 140% for Con A, and 136.6% for PWM mitogen. We conclude that MGN-3 possesses potent anti-HIV activity and in the absence of any notable side effects, MGN-3 shows promise as an agent for treating patients with AIDS.
1997

The effect of MGN-3, an arabinoxylan compound, on serum lipids and taste preference in streptozotocin-induced diabetic rats

Presenters: Ohara, Tabuchi and Maeda (Japan)
Event: 38th Annual Meeting of The American College of Nutrition ( MGN-3 was shown to reduce the rise in serum triglyceride and total cholesterol in diabetic rats indicating that it may be useful in the treatment of diabetes.)

1996

Anti-HIV activity by MGN-3 in vitro Presenter: M. Ghoneum

Event: 11th International Conference on AIDS in Vancouver (MGN-3 possesses a potent effect against syncytia formation by HIV and may be of potential value in therapy for HIV infection.)

1996

Effect of MGN-3 on human natural killer cell activity and interferon-gsynthesis in vitro

Presenter: M. Ghoneum
Event: ASBMB/ASIP/AAI joint meeting in New Orleans entitled.(MGN-3 is a potent Biological Response Modifier (BRM) as indicated by the significant increases in human NK cell activity at 16 hours post exposure through the production of IFN-G. MGN-3 also had direct anti-cancer activity in vitro.)

1996

Acute Oral Toxicity Test

Test: LD50
Lab: AMA Laboratories, New York, USA (Ref: WP96-BERN1/LD504881.DP).(Animal Experiment involving rats to determine any potential toxicity of MGN-3. Above material can be classified as non-toxic according to the reference. LD50 > 36.0g / kg.)

1996

NK immunomodulatory function in 27 cancer patients by MGN-3, a modified arabinoxylan from rice bran

Presenter: M. Ghoneum of UCLA/Drew University
Event: 87th Annual Meeting of the American Association for Cancer Research.(7 patients had breast cancer, prostate; 8 multiple myeloma (MM); 3 leukemia and 2 cervical. All patients taking conventional treatments as well as 3g MGN-3per day. All patients had significant rises in NK cell activity when taking MGN-3(100 – 537% increases.)

1995

Immunomodulatory and anti-cancer properties of MGN-3, a modified xylose from rice bran, in 5 patients with breast cancer

Presenter: M. Ghoneum of UCLA/Drew University
Event: American Association for Cancer Research at Baltimore, Maryland, USA. NK cell activity substantially increased within just a couple of weeks taking MGN-3 at a dose of 3g /day. Two patients who participated early in the study (6-8 months) went into complete remission.

1995

H. Maeda successfully develops commercially viable Biobran MGN-3

Event: Using special extraction methods on rice bran at Daiwa Pharmaceutical in Japan, Maeda develops Biobran. This proves much more potent than the AHCC he developed a few years earlier. Clinical trials with this new generation arabinoxylan compound begin.

1992

Enhancement of NK cell activity in cancer patients by AHCC

Presenter: M. Ghoneum
Event: The Adjuvant Nutrition in Cancer Treatment conference in Tulsa Oklahoma.

1992

Enhancement of human NK cell activity in vivo by AHCC

Presenter: M. Ghoneum
Event: 7th Annual Conference on clinical Immunology in Philadelphia.

1992

Active hemicellulous compound (AHCC) enhance NK cell activity of aged mice in vivo

Presenter: M. Ghoneum
Event: FASEB meeting in Anaheim, California.This compound was developed by H. Maeda as a precursor to MGN-3.

1989

A basic study of activation of host defence mechanism by food

Author: M. Yamazaki at the Faculty of Pharmaceutical Science at Teikyo University.