"Les études sont à la base de la qualité d'ImunoBran"

Nos recherches - Unsere Forschung - Our research

ImunoBran® = BioBran®

Études sélectionnées par type de cancerAusgewählte Studien nach Krebsart - Selected studies by cancer type

Nouveau rapport de cas - Neuer Fallbericht - New case report

Enhancing effect of streptozotocin-induced insulin deficit on antitumor innate immune defense in rats.

  • Hajto Tibor, Péczely László, Kuzma Monika, Hormay Edina, Ollmann Tamás, Jaksó Pál, Baranyai Lilla and Karádi Zoltán


Background: There are conflicting data about the relationship between diabetes mellitus and cancer risk in that growing evidence suggest a possible role of endogenous elevated insulin level which is often found in Non-Insulin-Dependent-Diabetes-Mellitus or an exogenous hyperinsulinemia observed often in Insulin-Dependent-Diabetes-Mellitus. In the last years higher attention focused on the role of immunoregulation both in the insulin production by β-cell of Langerhans-islets and in the insulin sensitivity (resistance) of insulin receptors. Interestingly, cytokines from type-2 innate immune cells, such as M2 macrophages or D2 dendritic cells exhibit a protective effect on both types of diabetes. However, the effect of insulin on the balance between type-1 and type-2 natural immune mechanisms, which is important for the tumour defence, was poorly investigated. 

Material and methods: Streptozotocin (STX)-treated Wister rats was treated per oral with a non-optimal single dose of an evidence based and standardized plant immunomodulator, namely Rice Bran Arabinoxylan Concentrate (RBAC) which has been shown to activate type-1 innate immune cells (such as M1, D1 and NK cells). 24h after a single dose of RBAC (45mg/kg) four parameters of NK cells were determined with flow cytometry using stained CD161-APC and CD314-PE monoclonal antibodies and by haematological examinations. The results were compared with negative controls (without STX or RBAC treatment).

Results: Since STX caused a significantly reduced lymphocyte production in bone marrow, only the RBAC-induced relative increases in number of NKR-P1+ and LGL cells among the all lymphocyte population parallel with the frequency and intensity of the most important Killing Activator Receptor, namely NKG2D among the total NK cell population were determined. In the STX-untreated group RBAC induced only not significant increases compared with negative control values. However, in STX-treated groups all four NK parameters revealed RBAC-induced significant increases (p<0.05) compared to the negative controls.

Conclusion: These results suggest the hypothesis that insulin deficit can increase the immunomodulator-induced activation of type-1 innate immune cells indicating that insulin takes part on regulation of the natural immune balance inhibiting the type-1 innate antitumor defence.

BioBran/ImunoBran-augmented maturation of human monocyte-derived dendritic cells

  • D.Cholujova, J.Jakubikova, J.Sedlak, (edited by Chris Gutch PhD.)

Abstract: BioBran, enzymatically modified arabinoxylan from rice bran was tested for its possible effects on in vitro maturation of human dendritic cells (DC). Immature DC (iDC) derived from plastic-adhered, IL-4 and GM-CSF treated peripheral monocytes (Mo) were further cultured with cytokine maturation mix 1 (CMM1; TNF-α, IL-1β and IL-6) or CMM2 (LPS and IFN-γ) to induce their maturation into mature DC (matDC1 or matDC2, respectively). Different concentrations of BioBran (10, 100, 400 and 1000 μg/ml) 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/GMCSF/BioBran down-regulated CD14 and CD1a 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 CD14 and upregulated CD83, CD80 and CD86 antigens, in comparison to DC matured with the relevant CMM alone. BioBran also increased CD123 antigen on all DC subsets. Intristingly, 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 CD11cdim CD123bright 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.

RBAC and Its Role with the Immune System

  • Fred Pescatore, MD, MPH; Carmelo Prestano, LPN; Malka Kichikova

ABSTRACT: Context • Rice Bran Arabinoxylan Compound (RBAC) is a trusted and proven immunomodulator made from a rice bran extract that has been enzymatically modified with an enzyme complex from the shiitake mushroom. Objective • The study's primary objective was to identify the role of RBAC in supporting cancer therapies. Design • The author designed an open study. Participants • Participants were 14 patients who are suffering from various type of malignancies. Intervention • BRM4 capsules-a commercially available, proprietary RBAC supplement-were administered. Outcome Measures • The study measured circulating tumor cells (CTC) and tumor markers-the prostate-specific antigen (PSA) and cancer antigens 125 (CA125) 15-3 (CA15-3), and 27-29 (CA27-29) for the relevant malignancy. Results • Twelve out of 14 participants completed the protocol, and two participants died during the study. Of the 12 participants completing the study, the CTC levels were reduced in 10, with a statistically significant difference between the testing at baseline and postintervention (P = .0047). The tumor markers of various malignancies decreased for nine out the 12 participants, and one participant experienced remission. Conclusions • The results suggest that the product can be an effective immunomodulator that can complement conventional cancer treatment. (Altern Ther Health Med. 2022;28(1):8-10).


Dietary Supplementation with Biobran/ImunoBran/MGN-3 Increases Innate Resistance and Reduces the Incidence of Influenza-like Illnesses in Elderly Subjects: A Randomized, Double-Blind, Placebo-Controlled Pilot Clinical Trial

  • Ahmed F. Elsaid , Sudhanshu Agrawal , Anshu Agrawal and Mamdooh Ghoneum, (edited by Chris Gutch PhD.), 2021

Abstract: Influenza-like illness (ILI) remains a major cause of severe mortality and morbidity in the elderly. Aging is associated with a decreased ability to sense pathogens and mount effective innate and adaptive immune responses, thus mandating the development of protective nutraceuticals. Biobran/MGN-3, an arabinoxylan from rice bran, has potent anti-aging and immunomodulatory effects, suggesting that it may be effective against ILI. The objective of the current study was to investigate the effect of Biobran/MGN-3 on ILI incidence, natural killer (NK) cell activity, and the expressions of RIG-1 (retinoic acid-inducible gene 1), MDA5 (melanoma differentiation-associated protein 5), and their downstream signaling genes ISG-15 (interferon-stimulated genes 15) and MX1 (myxovirus (influenza) resistance 1, interferon-inducible). A double-blind, placebo-controlled clinical trial included eighty healthy older adults over 55 years old, 40 males and 40 females, who received either a placebo or Biobran/MGN-3 (500 mg/day) for 3 months during known ILI seasonality (peak incidence) in Egypt. The incidence of ILI was confirmed clinically according to the WHO case definition criteria. Hematological, hepatic, and renal parameters were assessed in all subjects, while the activity of NK and NKT (natural killer T) cells was assessed in six randomly chosen subjects in each group by the degranulation assay. The effect of Biobran/MGN-3 on RIG-1 and MDA5, as well as downstream ISG15 and MX1, was assessed in BEAS-2B pulmonary epithelial cells using flow cytometry. The incidence rate and incidence density of ILI in the Biobran/MGN-3 group were 5.0% and 0.57 cases per 1000 person-days, respectively, compared to 22.5% and 2.95 cases per 1000 person-days in the placebo group. Furthermore, Biobran/MGN-3 ingestion significantly enhanced NK activity compared to the basal levels and to the placebo group. In addition, Biobran/MGN-3 significantly upregulated the expression levels of RIG-1, MDA5, ISG15, and MX1 in the human pulmonary epithelial BEAS-2B cell lines. No side effects were observed. Taken together, Biobran/MGN-3 supplementation enhanced the innate immune response of elderly subjects by upregulating the NK activity associated with reduction of ILI incidence. It also upregulated the intracellular RIG-1, MDA5, ISG15, and MX1 expression in pulmonary epithelial tissue cultures. Biobran/MGN-3 could be a novel agent with prophylactic effects against a wide spectrum of respiratory viral infections that warrants further investigation.


Arabinoxylan rice bran (MGN-3/Biobran) alleviates radiation-induced intestinal barrier dysfunction of mice in a mitochondrion-dependent manner                        PEER REVIEWED

  • Zhenguo Zhao , Wei Chengb, Wei Qu , Kai Wang, (edited by Chris Gutch PhD.), 2020

Abstract: MGN-3 is an arabinoxylan from rice bran that has been shown to be an excellent antioxidant and radioprotector.  This study examined the protective effects of MGN-3 on radiation-induced intestinal injury. Mice were treated with MGN-3 prior to irradiation, then continued to receive MGN-3 for 4 weeks thereafter. MGN-3 increased the activity of mitochondrial respiratory chain complexes Ⅰ, Ⅲ, Ⅳ and Ⅴ, the intercellular ATP content, the mitochondria-encoded gene expression and mitochondrial copy numbers in the jejunal and colonic mucosa. MGN-3 reduced the oxidative stress levels and inflammatory response indicators in the serum and jejunal and colonic mucosa. Antioxidant indicators such as superoxide dismutase, glutathione peroxidase, catalase and total antioxidant capacity were significantly increased in the serum and jejunal and colonic mucosa in the MGN-3 group. Moreover, MGN-3 decreased the gene abundances and enzymatic activities of caspase-3, 8, 9 and 10 in the jejunal and colonic mucosa. The endotoxin, diamine peroxidase, D-lactate and zonulin levels were significantly reduced in the serum and jejunal and colonic mucosa in the MGN-3 group. MGN-3 also markedly upregulated the gene abundances of ZO-1, occludin, claudin-1 and mucin 2. MGN-3 effectively attenuated radiation-induced changes in the intestinal epithelial mitochondrial function, oxidative stress, inflammatory response, apoptosis, intestinal permeability and barrier function in mice. These findings add to our understanding of the potential mechanisms by which MGN-3 alleviates radioactive intestinal injury.

Chemopreventive role of arabinoxylan rice bran, MGN-3/Biobran, on liver carcinogenesis in rats                                                                                                                     PEER REVIEWED

  • Nariman K. Badr El-Din, Doaa A. Ali, Reem Othman, Samuel W. French, Mamdooh Ghoneum, (edited by Chris Gutch PhD.), 2020

 Abstract: Hepatocellular carcinoma (HCC) is one of the most common cancers in the world and one of the most lethal. MGN-3/Biobran is a natural product derived from rice bran hemicelluloses and has been reported to possess a potent anticancer effect in a clinical study of patients with HCC. The current study examines the mechanisms by which Biobran protects against chemically induced hepatocarcinogenesis in rats. The chemical carcinogen used in this study is N-nitrosodiethylamine (NDEA) plus carbon tetrachloride (CCl4). Rats were treated with this carcinogen, and the animals were pretreated or posttreated with Biobran via intraperitoneal injections until the end of the experiment. Treatment with Biobran resulted in: 1) significant alleviation of liver preneoplastic lesions towards normal hepatocellular architecture in association with inhibition of collagen fiber deposition; 2) arrest of cancer cells in the sub-G1 phase of the cell cycle; 3) increased DNA fragmentation in cancer cells; 4) down-regulated expression of Bcl-2 and up-regulated expression of p53, Bax, and caspase-3; and 5) protection against carcinogen-induced suppression of IkappaB-alpha (IκB-α) mRNA expression and inhibition of nuclear factor kappa-B (NF-κB/p65) expression. Additionally, the effect of Biobran treatment was found to be more significant when supplemented prior to carcinogen-induced hepatocarcinogenesis as compared to posttreatment. We conclude that Biobran inhibits hepatocarcinogenesis in rats by mechanisms that include induction of apoptosis, inhibition of inflammation, and suppression of cancer cell proliferation. Biobran may be a promising chemopreventive and chemotherapeutic agent for liver carcinogenesis

The Immunomodulating Effects of Arabinoxylan Rice Bran (Lentin) on Hematologic Profile, Nutritional Status and Quality of Life among Head and Neck Carcinoma Patients Undergoing Radiation Therapy: A Double Blind Randomized Control Trial


  • Dorothy Faye S. Tan, MD; Jerickson Abbie S. Flores, MD, (edited by Chris Gutch PhD.), 2020

Abstract: Immunostimulants have been explored to reduce the complications of radiation/chemotherapy. This double blind randomized trial aimed to determine the immunomodulating effects of Lentin among head and neck cancer patients in addressing radiation treatment complications such as anemia, leukopenia, weight loss and improvement of quality of life. Sixty-five (65) patients were enrolled and given either Lentin or placebo - 2 weeks prior, during radiation/chemoradiotherapy and 2 months after. Complete Blood Count, Body Mass Index, percent weight loss and EORTC Quality of Life questionnaires QLQ H&N35 were used to assess the degree of anemia, weight loss and quality of life. Overall CBC results revealed higher values on all parameters in Lentin arm. Upon completion of radiochemotherapy, the Lentin arm showed significantly higher mean hemoglobin by 1.30 g/dL (p=0.010), hematocrit (p=0.001), RBC (p=0.001) and platelets (p=0.017). Also, higher overall BMI (22.69 versus 21.52) and a lower percent weight loss (6.10% versus 6.91%) for Lentin compared to placebo were noted with p-values of 0.199 and 0.571, respectively. Treatment related toxicity using the RTOG grading showed lower severity scores on all parameters (p-values: >0.05) and better QoL scores for patients taking Lentin (p-value: 0.019). Results from this study showed better clinical outcomes for patients taking Lentin. These have led to fewer blood transfusions, treatment delays and hospital admissions, avoidance of treatment mortalities and morbidities, and improved quality of life among head and neck cancer patients undergoing chemoradiotherapy.

Arabinoxylan rice bran (MGN-3/Biobran) enhances radiotherapy in animals bearing Ehrlich ascites carcinoma

  • Nariman K. Badr El-Din,*, Said K. Areida , Kvan O. Ahmed and Mamdooh Ghoneum, (edited by Chris Gutch PhD.), 2019

Abstract: This study examines the ability of arabinoxylan rice bran (MGN-3/Biobran) to enhance the anti-cancer effects of fractionated X-ray irradiation of Ehrlich solid tumor-bearing mice. Swiss albino mice bearing tumors were exposed to the following: (i) Biobran treatment (40 mg/kg/day, intraperitoneal injections) beginning on day 11 post-tumor cell inoculation until day 30; (ii) ionizing radiation (Rad) 2 Gy at three consecutive doses on days 12, 14 and 16; or (iii) Biobran + Rad. Final tumor weight was suppressed by 46% for Biobran, 31% for Rad and 57% for the combined treatment (Biobran + Rad) relative to control untreated mice. Biobran and Rad also arrested the hypodiploid cells in the sub-G1-phase, signifying apoptosis by +102% and +85%, respectively, while the combined treatment induced apoptosis by +123%, with similar results in the degree of DNA fragmentation. Furthermore, Biobran + Rad upregulated the relative gene expression and protein level of p53 and Bax in tumor cells, down-regulated Bcl-2 expression, and increased the Bax/Bcl-2 ratio and caspase-3 activity, with the combined treatment greater than for either treatment alone. Additionally, the combined treatment modulated the decrease in body weight, the increase in liver and spleen weight, and the elevation of liver enzymes aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transferase to be within normal values. We conclude that Biobran enhances radiation therapy-induced tumor regression by potentiating apoptosis and minimizing toxicities related to radiation therapy, suggesting that Biobran may be useful in human cancer patients undergoing radiotherapy and warranting clinical trials.

The Novel Effects of a Hydrolyzed Polysaccharide Dietary Supplement on Immune, Hepatic, and Renal Function in Adults with HIV in a Randomized, Double-Blind Placebo-Control Trial

  • John E. Lewis, Steven E. Atlas, Muhammad H. Abbas, Ammar Rasul, Ashar Farooqi, Laura A. Lantigua, Frederick Michaud, Sharon Goldberg, Lucas C. Lages, Oscar L. Higuera, Andrea Fiallo, Eduard Tiozzo, Judi M. Woolger, Stephanie Ciraula, Armando Mendez, Allan Rodriguez & Janet Konefal, (edited by Chris Gutch PhD.), 2018

Abstract: The primary objective of the study was to evaluate the effects of a hydrolyzed polysaccharide, rice bran arabinoxylan compound (RBAC), on immune, hepatic, and renal function in HIV þ individuals. A six-month randomized double-blind placebo-controlled trial was utilized to conduct the intervention. Forty-seven HIV þ participants on stable antiretroviral therapy were enrolled and randomly assigned to one of the two study conditions (n 1⁄4 22 RBAC and n 1⁄4 25 placebo) and consumed 3 gram/day of either compound for six months. Participants were assessed at baseline and 3 and 6 months follow-up for CD4þ and CD8þ, liver enzymes, and kidney function. No side effects were reported, and liver and kidney markers nearly remained completely within normal limits. The percentage change in CD4þ was similar for the placebo (þ2.2%) and RBAC (þ3.1%) groups at 6 months follow-up. The percentage change in CD8þ count significantly decreased from baseline to 6 months in the RBAC group(-5.2%), whereas it increased in the placebo group (þ57.8%; p 1⁄4 0.04). The CD4þ/CD8þ ratio improved clinically in the RBAC group from 0.95 (SD 1⁄40.62) at baseline to 1.07 (SD 1⁄40.11) at 6 months, whereas it declined in the placebo group from 0.96 (SD 1⁄40.80) at baseline to 0.72 (SD 1⁄40.59) at 6 months. Our results showed a statistically significant decrease in CD8þ count and a clinically significant increase in CD4þ/CD8þ ratio for the RBAC group compared to the placebo group. Thus, the results of this study suggest that the immunomodulatory and antisenescent activities of RBAC are promising for the HIV population.

New Perspectives to Improve the MHC-I Unrestricted Immune Mechanisms against Malignant Tumors

  • Tibor Hajto, (edited by Chris Gutch PhD.), 2018

Abstract: Since malignant tumors parallel with their progression can lose their sensitivity against the MHC-I restricted T lymphocytes because of their escape in tumor antigen presenting, we need immunomodulators which are able to activate MHC-I unrestricted tumoricidal mechanisms of innate immune system. In contrast to the adaptive system, the innate immune cells have regularly a basic activity (priming) which can determine their function ability and render possible a polarity similar to neuroendocrine system. Namely, innate immune cells are committed in two directions. Type-1 cells involve tumoricidal cascade mechanisms which activate the MHC-I unrestricted killer cells (such as NK-cells) and Type-2 cells activate cell proliferation by production of Growth Factors (GFs), affect chronic inflammation, stimulate the angiogenesis and inhibit the type-1 system. As shown in this paper the activity of type 1 cells is down regulated parallel with the tumor progression and available information suggest a regular tumor-induced dominance of type-2 cells. Immunomodulators must improve this disturbed balance. Type-1 natural cells can be activated only via stimulation of phagocytic cells by PAMP like structures which have always a natural origin and the chemistry is not able to produce them. In the tumoricidal activity of MHC-I unrestricted killer cells the expression of NKG2D receptors and the expression of their stress related ligands (MICA/B, UBPL1-3) have pivotal regulatory role generating the kill signal. The aim of this review paper to support hypotheses as to whether an increase in expression of KAR on MHC-I unrestricted killer cells by evidence based plant immunomodulators and parallel stimulating the expression of stress related ligands on tumor cells by GFR inhibitors or cytostatic drugs (such as Gemcitabin) can result in clinical benefits. Case reports using standardized Rice Bran Arabinoxylan Concentrate (Biobran/MGN-3) in combination with GFR inhibitors or Gemcitabin show astonishing clinical responses. Unfortunately, in spite of clinical and immunological evidences this plant immunomodulator is registered only as food supplements and a further research of these hypotheses is therefore hindered.

The Effect of a Hydrolyzed Polysaccharide Dietary Supplement on Biomarkers in Adults with Nonalcoholic Fatty Liver Disease

  • John E. Lewis , Steven E. Atlas, Oscar L. Higuera, Andrea Fiallo, Ammar Rasul, Ashar Farooqi, Olga Kromo, Laura A. Lantigua, Eduard Tiozzo , Judi M. Woolger, Sharon Goldberg, Armando Mendez , Allan E. Rodriguez, and Janet Konefal, (edited by Chris Gutch PhD.), 2018

Abstract: The primary objective of the study was to evaluate the effect of a hydrolyzed polysaccharide, Rice Bran Arabinoxylan Compound (RBAC), on biomarkers in adults with nonalcoholic fatty liver disease (NAFLD). A 90-day randomized double-blind placebo-controlled trial examined the effect of RBAC on complete blood count, liver enzymes, lipids, oxidative stress markers, cytokines, and growth factors. Twenty-three adults with NAFLD were enrolled and randomly assigned to one of the two study conditions (n = 12 RBAC and n = 11 placebo) and consumed 1 gram/day of either compound for 90 days. Subjects were assessed at baseline and 45 and 90 days. No adverse effects were reported. Alkaline phosphatase significantly decreased (−3.1%; SD = 19.9; F[1, 19] = 5.1, p = 0.03) in the RBAC group compared to placebo. Percent monocytes (17.9%; SD = 18.3; F[1, 19] = 5.9, p = 0.02) and percent eosinophils (30.6%; SD = 30.5; F[1, 19] = 12.3, p < 0.01) increased in the RBAC group. IFN-γ (156%; SD = 131.8; F[1, 19] = 4.2, p = 0.06) and IL-18 (29.1%; SD = 64; F[1, 19] = 5.3, p = 0.03) increased in the RBAC group compared to placebo. Other improvements were noted for platelets, neutrophils, neutrophil-lymphocyte ratio, γ-glutamyl transferase, and 4-hydroxynonenal. RBAC had beneficial effects on several biomarkers that add to the known immunomodulatory activities of RBAC, which may be promising for people with NAFLD.

Evidence-Based Review of BioBran/ MGN-3 Arabinoxylan Compound as a Complementary Therapy for Conventional Cancer Treatment

  • Soo Liang Ooi, MMath, BHSc (Comp Med) , Debbie McMullen, BHSc (Comp Med), Terry Golombick, PhD, Dipl Nut , and Sok Cheon Pak, PhD, (edited by Chris Gutch PhD.), 2017

Abstract Introduction: Conventional cancer treatment, including surgery, chemotherapy, and radiotherapy, may not be sufficient to eradicate all malignant cells and prevent recurrence. Intensive treatment often leads to a depressed immune system, drug resistance, and toxicity, hampering the treatment outcomes. BioBran/MGN-3 Arabinoxylan is a standardized arabinoxylan concentrate which has been proposed as a plant-based immunomodulator that can restore the tumor-induced disturbance of the natural immune system, including natural killer cell activity to fight cancer, complementing conventional therapies. Objectives: To comprehensively review the available evidence on the effects and efficacies of MGN-3 as a complementary therapy for conventional cancer treatment. Methods: Systematic search of journal databases and gray literature for primary studies reporting the effects of MGN-3 on cancer and cancer treatment. Results: Thirty full-text articles and 2 conference abstracts were included in this review. MGN-3 has been shown to possess immunomodulating anticancer effects and can work synergistically with chemotherapeutic agents, in vitro. In murine models, MGN-3 has been shown to act against carcinogenic agents, and inhibit tumor growth, either by itself or in combination with other anticancer compounds. Fourteen successful MGN-3 treated clinical cases were found. Eleven clinical studies, including 5 nonrandomized, pre-post intervention studies and 6 randomized controlled trials (RCTs) were located. Reported effects include enhanced immunoprofile, reduced side effects, improved treatment outcomes; one RCT established significantly increased survival rates. There are no reports on adverse events on MGN-3. Most of the clinical trials are small studies with short duration. Conclusion: There is sufficient evidence suggesting MGN-3 to be an effective immunomodulator that can complement conventional cancer treatment. However, more well-designed RCTs on MGN-3 are needed to strengthen the evidence base.

Biobran/MGN-3, an arabinoxylan rice bran, enhances NK cell activity in geriatric subjects: A randomized, double-blind, placebo-controlled clinical trial

  • AHMED F. ELSAID, MAGDA SHAHEEN and MAMDOOH GHONEUM, (edited by Chris Gutch PhD.), 2017

Abstract: Aging is associated with a decline in natural killer (NK) and natural killer T (NKT) cell function that may contribute to increased susceptibility to malignancy and infection. A preliminary investigation was conducted examining the hypothesis that arabinoxylan rice bran (Biobran/MGN-3), a denatured hemicellulose with known immunomodulatory activity, could counteract this decline in NK/NKT cell activity in geriatrics. A total of 12 healthy geriatric subjects of both sexes and over 56 years old, participated in a randomized, double-blind, placebo-controlled clinical trial. A total of six subjects served as control and six subjects ingested Biobran/MGN-3 (500 mg/day) for 30 days. The effect of Biobran/MGN-3 supplementation on NK/NKT cell activity was assessed using the degranulation assay. All study subjects were monitored for the development of any inadvertent side effects. In addition, the pharmacological effects of Biobran/MGN-3 on blood cell components and liver and kidney functions were also assessed. Results demonstrated that Biobran/MGN-3 had no effect on the total percentage of NK cells, however it enhanced the cytotoxic activity of induced NK cell expression of cluster of differentiation 107a, when compared with baseline values and with the placebo group (P<0.05). Furthermore, there were no side effects observed, indicating that Biobran/MGN-3 supplementation was safe at the utilized dosage and for the duration of administration. Various additional beneficial effects were observed, including improved mean corpuscular volume and reduced hepatic aspartate aminotransferase enzyme levels, which suggested improved liver function. It was concluded that Biobran/MGN-3 induces a significant increase in NK activity which may increase resistance to viral infections and cancers in the geriatric population.

However, additional clinical trials should be conducted in the future to verify these findings.

Can a standardized plant immunomodulator (rice bran arabinoxylan concentrate/MGN-3) increase the effects of MEK and BRAF inhibitors with clinical benefit? Case report of a patient with carcinoma in biliary duct

  • Tibor Hajto, (edited by Chris Gutch PhD.), 2017

Background: Targeting hyperactive mitogen-activated protein kinase (MAPK) signaling cascade has proven to be an effective treatment for a variety of different cancers. Using an important member of this cascade, namely MEK (mitogen activated extracellular signal regulation kinase) inhibitors, the clinical responses are often transient and complete remission is rarely observed. Outgrowth of resistant clones within progressed tumors appears to be inevitable. Recent immunological and clinical observations suggest that in background of this resistance the tumor-.induced disturbance of immunoregulation at least in part may play a role. Namely, it was shown that growth factor receptor signaling pathway inhibitors can increase the immune sensitivity of tumor cells, but they can't activate the down regulated immune effectors. Consequently, the combination of MAPK cascade signaling pathway inhibitors and the immune effectors activating immunomodulators may be a promising new strategy. Material and methods: In a now 59 years old patient with inoperable (BRAF-mutant) low differentiated adenocarcinoma of bilary ducts after 30GY radiotherapy and two cycles (Gemcitabin+ Cisplatin) chemotherapy a rapid progression of lung, liver and brain metastases were by CT and MR established. Thereafter, a teatment with BRAF+MEK inhibitors (2x150 mg dabrafenib and 1 x 2 mg trametinib) was started. These inhibitors were combined with daily 45 mg/kg rice bran arabinoxylan concentrate (using Biobran/MGN-3) which was shown to be a pathogenic associated molecular pattern (PAMP)-like molecule and can stimulate the type-1 innate immune cells against tumor cells. Results: After the chemotherapy and prior to the start of second line treatment, the patient had a nearly terminal state of her rapidly progressive disease. Eight months after the combination of MEK / BRAF inhibitor and immunomodulator therapy nearly complete remissions of all metastases was established in CT and MR. 

Conclusion: This case report may support a hypothesis that MEK / BRAF inhibitors and type-1 immune cells activating immunomodulators together may synergistic inhibit the tumor growth. Further clinical investigations are necessary to clarify this question.

Un immunomodulateur végétal standardisé, fondé sur les faits (composé d'arabinoxylane de son de riz) peut-il accroître les effets de la gemcitabine de façon synergique? Étude de cas sur un patient présentant un carcinome canalaire du pancréas. Tibor Hajto*, Université de Médecine de Pecs, Hongrie

Können Inhibitoren EGFR die Immunomodulation standardisierter Pflanzenauszüge (Lektin aus Mistel und Arabinoxylan) mit günstigem klinischen Ergebnis erhöhen? Fallstudie einer Patientin mit Lungenadenokarzinom. Tibor Hajto*, Medizinische Universität von Pecs, Ungarn

Urgent Necessity for Standardized and Evidence Based Plant Immunomodulators (Such As Rice Bran Arabinoxylan Concentrate/MGN-3) for the Tumor Research

  • Tibor Hajto, (edited by Chris Gutch PhD.), 2017

Objective: Biological targeting therapies can inhibit the cascade of cell proliferation and enhance the sensitivity of malignant tumor cells against natural immune effector cells. Clinical observations suggest that their combination with evidence based and standardized plant immunomodulators (such as arabinoxylan concentrate using Biobran/MGN-3) can induce astonishing results. Since the escape of tumor cells from T lymphocytes is well known, growing interest is focusing on the Pathogenic Associated Molecular Pattern (PAMP) molecules which are able to stimulate the so called type-1 natural antitumor mechanisms in a MHC unrestricted manner. However, PAMP molecules exist only in the nature (bacteria and plants). The chemistry is not able to produce them. Bacteria are toxic. Therefore growing interest developed for the PAMP like molecules in the plants. Unfortunately, in terms of PAMP like molecules standardized plant immunomodulators (such as arabinoxylan concentrate in Biobran/MGN-3) are registered world over as food supplement and therefore their further clinical research in various oncological centers is inhibited. 

Can the EGFR inhibitors increase the immunomodulatory effects of standardized plant extracts (mistletoe lectin and arabonoxylan) with clinical benefit? Case report of a patient with lung adenocarcinoma

  • Tibor Hajto*, Anna Horváth, Lilla Baranyai, Monika Kuzma and Pál Perjési, 2016

Background: It is well documented that cancer cells are characterized by loss or down regulation of HLA-class-I molecules which are not reversible and reparable. It leads to a definitive escape of tumor cells from T cell lyse. Consequently, growing attention is focusing on the effector cells of innate immune system which are able to kill tumor cells in a non-MHC restricted manner. However, parallel with the tumor progression the tumor growth inhibiting type-1 innate immune cells are down regulated, in that among other reasons a tumor-associated dysregulation of EGF signaling can also play an important role.

Material and methods: Since a 74 year's old patient with inoperable lung adenocarcinoma showed a progression after four cycles Carboplatin and Paclitaxel, a second line treatment with 75 mg/day Erlotinib (Terceva) was started and given for seven months. This tyrosin-kinase inhibitor of Epidermal Growth Factor Receptor (EGFR) therapy was combined with standardized plant immunomodulators giving 0.75 ng/kg mistletoe lectin and 0.45 mg/kg arabinoxylan twice a week which were shown to be pathogenic associated molecular pattern (PAMP)-like molecules which can stimulate the type-1 innate immune cells.

Results: After the chemotherapy and prior to the start of second line treatment the patient was in terminal state of her disease requiring an intensive care. She had multiplex metastases in liver, in lymph nodes and in pleura. After the treatment with Erlotinib and immunomodulators for seven months a nearly complete remission (CR) was established in CT and her quality of life has been excellent. 

Conclusion: This case report may support a hypothesis that EGFR inhibitors and type-1 immune cells activating immunomodulators together can synergistic inhibit the tumor growth. Further clinical investigations are necessary to clarify this question.

Les inhibiteurs des récepteurs de l'EGF peuvent-ils accroître les effets immunomodulateurs des extraits de plantes standardisés (de lectine de gui et d'arabinoxylane) avec un résultat clinique avéré? Rapport de cas d'un patient souffrant d'adénocarcinome pulmonaire.

Können Inhibitoren EGFR die Immunomodulation standardisierter Pflanzenauszüge (Lektin aus Mistel und Arabinoxylan) mit günstigem klinischen Ergebnis erhöhen? Fallstudie einer Patientin mit Lungenadenokarzinom.

From Bench to Bedside: The Growing use of Arabinoxylan Rice Bran (MGN-3 /Biobran) in Cancer Immunotherapy

  • Mamdooh Ghoneum, Dept of Otolaryngology, Charles Drew University of Medicine and Science, USA, (edited by Chris Gutch PhD.), 2016

Objective: MGN-3/Biobran is a denatured hemicellulose obtained by reacting rice bran hemicellulose with multiple carbohydrate hydrolyzing enzymes from Shiitake mushrooms. Over the last 24 years, our fundamental research objective has been to study the biotherpeutic activity of MGN-3 as a treatment for cancer based on its ability to activate the immune system. This objective has been pursued in vitro, and in animal and human studies. This review is focused on the immunomodulatory effects of MGN-3 and on its potential as an anticancer agent. In vitro studies showed that culturing different human and murine cancer cell lines with MGN-3 resulted in a reduction of the survival rate of cancer cells. In vivo studies have also shown that MGN-3 induces tumor regression in several models of animal bearing tumor, including gastric cancer, neuroblastoma, and Ehrlich carcinoma. In addition, the anti-cancer activity of MGN-3 has been shown in human clinical trials and in several case reports on patients with Hepatocellular Carcinoma (HCC) and progressive and partially metastasized cancer. Patients that were treated with MGN-3 in addition to Conventional Therapy (CT), as compared with CT alone, showed: 1) less recurrence of cancer, 2) higher survival rate and 3) improved Quality of Life (QOL) as characterized by improvements in physical activity, appetite, sleep, and digestion, and a decrease in pain and anxiety. This review summarizes the preclinical and clinical research on MGN-3/Biobran since it was frst patented in 1992. Various animal studies and human clinical trials including different types of malignancies have demonstrated that MGN-3 is a potent Biological Response Modifer (BRM). MGN-3 enhances the cytotoxic reactivity of immune cells with anti-cancer activity such as NK and CD8+ T cells via increasing cell granularity, stimulates the production of interferons, IL-2 and IL-12, and functions as a natural adjuvant for Dendritic Cells (DC). Therefore, MGN-3 may be used in DC-based vaccine strategies against infections and cancer. Importantly, MGN-3 is a unique BRM because it is a safe non-toxic agent and does not exhibit hyporesponsiveness. MGN-3 has the potential to be a novel and promising immune modulatory adjuvant that could complement the existing immunotherapeutic modalities for cancer patients.

Du laboratoire à la table de nuit : l'arabinoxylane de son de riz (MGN-3/ImunoBran®) utilisé de plus en plus dans le traitement immunologique de cancer

Vom Labor auf den Nachttisch: Steigende Anwendung von Arabinoxylan aus Reiskleie (MGN- 3/ImunoBran®) in der immunologischen Therapie von Krebserkrankungen

Arabinoxylan rice bran (Biobran) suppresses the viremia level in patients with chronic HCV infection: A randomized trial 

  • Hosny Salama, Eman Medhat, Magda Shaheen, Abdel-Rahman N Zekri, Tarneem Darwish and Mamdooh Ghoneum, (edited by Chris Gutch PhD.), 2016

Objective: Current treatments for Hepatitis C virus (HCV) have severe side effects and are very expensive. There is a need to explore effective natural therapies against HCV that are less toxic and more cost-effective. In the current study, 37 chronic HCV patients were randomized into two groups and treated with either pegylated interferon (PEG IFN) plus ribavirin (n = 21) or Biobran, an arabinoxylan from rice bran (1 g/day) (n = 16). We examined viremia, liver enzymes, interferon-γ (IFN-γ) levels in serum, and toxicity before and three months after treatment. Both groups showed a significant and similar reduction in viral load after three months of treatment relative to the baseline viral load (P <0.05). In addition, treatment with Biobran resulted in a significant increase in the level of IFN-γ (P <0.001). Patients in the PEG IFN plus ribavirin group showed fever, anemia, thrombocytopenia, and easy fatigue. Patients in the Biobran group showed no side effects and reported good health. We conclude that Biobran is a potential novel therapeutic regimen that has a similar effect to PEG IFN plus ribavirin and is safe and cost-effective in the treatment of chronic HCV. Our finding of Biobran's efficacy against HCV infection warrants further investigation in multiple clinical trials (Clinical Trials Registration: NCT02690103).

L'arabinoxylane de son de riz (ImunoBran®) réduit le taux de virémie chez les patients souffrant d'infection chronique HCV : essai randomisé*

Arabinoxylan aus Reiskleie (ImunoBran®) hemmt den Virämiespiegel bei Patienten mit chronischer HCV-Infektion: Randomisierte Studie*

Modified rice bran hemicellulose inhibits vascular endothelial growth factor-induced angiogenesis in vitro via VEGFR2 and its downstream signalling pathways

  • Xia ZHU, Aya OKUBO, Naoki IGARI, Kentaro NINOMIYA and Yukari EGASHIRA, (edited by Chris Gutch PhD.), 2016

Objective: Angiogenesis is implicated in diverse pathological conditions such as cancer, rheumatoid arthritis, psoriasis, atherosclerosis, and retinal neovascularization. In the present study, we investigated the effects of modified rice bran hemicellulose (MRBH), a water-soluble hemicellulose preparation from rice bran treated with shiitake enzymes, on vascular endothelial growth factor (VEGF)-induced angiogenesis in vitro and its mechanism. We found that MRBH significantly inhibited VEGF-induced tube formation in human umbilical vein endothelial cells (HUVECs) co-cultured with human dermal fibroblasts. We also observed that MRBH dose-dependently suppressed the VEGF-induced proliferation and migration of HUVECs. Furthermore, examination of the anti-angiogenic mechanism indicated that MRBH reduced not only VEGF-induced activation of VEGF receptor 2 but also of the downstream signalling proteins Akt, extracellular signal-regulated protein kinase 1/2, and p38 mitogen-activated protein kinase. These findings suggest that MRBH has in vitro anti-angiogenic effects that are partially mediated through the inhibition of VEGF signalling. Key words: angiogenesis, modified rice bran hemicellulose, VEGF, inhibition, signalling pathway

Controlled pilot study for cancer patients suffering from chronic fatigue syndrome due to chemotherapy treated with BioBran (MGN-3- Arabinoxylane) and targeted radiofrequency heat therapy                                                                                                        PEER REVIEWED 

  • Gabriel Petrovics, Gyula Szigeti, Szilárd Hamvas, Ágnes Máté, József Betlehem, Gabriella Hegyi*, (edited by Chris Gutch PhD.), 2016

Introduction: Although modern therapies for cancer have improved life expectancy, the management of disease and improvement of quality of life (QoL) of patients, especially managing cancer-related pain and chronic fatigue syndrome are still limited. We demonstrate the efficacy of a combined therapy to treat cancer patients suffering from CFS. The effects of a combined therapy in cancer patients suffering from CFS was evaluated. NK cells were stimulated, additional tumour treatment together with targeted radiofrequency therapy (Oncothermia). 

Methods: SIXTY patients with CFS (due to suffering from any type of cancer) were recruited, (according to the Centres for Disease Control 1994 criteria) attending an outpatient specialist CFS service for controlled pilot study. A total of 25 participants were given oral BioBran (MGN-3-Arabinoxylane), + Oncothermia, for six months, equivalent control group has not received this complex (BioBran + Oncothermia) treatment, they received chemo-,radiotherapy treatment. Results: The whole body pH status showed strong tissue acidity before the treatment, but the BioBran group changed the tissue pH status. The most important finding was that the average of CFQ score was significantly reduced after the treatment, and in control group the CFQ scores did not change significantly. Conclusion: The findings support a specific therapeutic effect of the complex BioBran+ Oncothermia therapy in CFS of cancer patients improving their QoL, enhancing NK activity in synergy.

© 2016 Published by Elsevier GmbH.

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

  • 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, (edited by Chris Gutch PhD.), 2015

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.

L'arabinoxylane de son de riz (MGN-3/Biobran®) améliore la cytoxicité par les cellules tueuses naturelles en présence de neuroblastome in vitro et in vivo.

Arabinoxylan aus Reiskleie (MGN-3/Biobran®) verbessert zellvermittelte Zytotoxizität der natürlichen Killerzellen gegen Neuroblastome in vitro und in vivo.

Home Products Research Distributors Contact Can a synergistic activation of pattern recognition receptors by plant immunomodulators enhance the effect of oncologic therapy? Case Report of a patient with uterus and ovary sarcoma

  • Tibor Hajto, Lilla Baranyai, Angelika Kirsch, Monika Kuzma and Pal Perjési, (edited by Chris Gutch PhD.), 2015

Background: Growing evidence supports the hypothesis that similar to microbes various plant extracts can also contain Pathogenic Associated Molecular Pattern (PAMP)-like structures which can activate type-1 cellular functions of the innate immune system. Since they are important in tumor defense and the chemical production of PAMP structures is hardly accomplishable, the plant extracts standardized concerning their PAMP like structures may be promising for future tumor therapy. Method: The synergistic effect of two standardized plant immunomodulators was monitored by the hemocytological measurement of the peripheral level of Natural Killer (NK) cells. Suboptimal doses of istletoe lectins (ML) and Arabinoxylan in MGN-3 were compared using healthy volunteers. Results: 24h after a single suboptimal dose (15 mg/kg) of Arabinoxylan in MGN-3 an average increase (+/-SEM) in NK level was 46.4 (+/-36)% and 24h after a single suboptimal (0.45 ng/kg) ML injection a 36 (+/-13) % enhancement was found. If these suboptimal doses of Arabinoxylan and ML were given together, a highly significant enhancement (293 +/-41%) was established indicating a high significant synergism between them (p<0.001). A patient with uterus and ovary sarcoma was not able to tolerate the CYVADIC chemotherapy. After its combination with ML and Arabinoxylan using optimal doses: 0.75 ng/kg and 45 mg/kg respectively, she received six cycles CYVADIC and thereafter only immunotherapy was given. During the following five years she has regularly been tumor free. Conclusion: The combination of standardized plant extracts with PAMP-like structures seems to open new perspectives in the supportive therapy of metastatic tumors. Further research is necessary. 

L'activation des récepteurs de reconnaissance de motifs moléculaires provoquée par l'effet synergique des immunomodulateurs de plantes peut-elle améliorer l'efficacité du traitement oncologique? Étude du cas d'une patiente souffrant d'un sarcome de l'utérus et de l'ovaire.

Kann die Aktivierung der, das Muster erkennenden Rezeptoren, die durch synergisches Einwirken pflanzlicher Immunomodulatoren hervorgerufen wird, die Wirkung der onkologischen Behandlung verbessern? Fallstudie an Patientin mit Gebärmutter- und Eierstocksarkom.

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

  • M. Ghoneum and S. Agrawal, (edited by Chris Gutch PhD.), 2014

Objective: 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.

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                                                                                                 PEER REVIEWED 

  • 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, (edited by Chris Gutch PhD.), 2014

Objective: 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 (P < 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.

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

  • Mamdooh Ghoneum, Nariman K. Badr El-Din, Doaa A. Ali and Mai Alaa El-Dein, (edited by Chris Gutch, PhD.), 2014

Objective: 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.

L'arabinoxylane modifié au son de riz, le MGN-3/Biobran®, sensibilise les cellules métastatiques du carcinome du sein au paclitaxel in vitro

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

  • Tibor Hajto and Angelika Kirsch, (edited by Chris Gutch PhD.), 2013

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.

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

  • Masood AI, Sheikh R, Anwer RA, (edited by Chris Gutch PhD.), 2013

Objective: The aim of study was to assess the effect of Biobran in reducing of chemotherapy induced side effects in terms of tiredness, anorexia, vomiting and hair loss and quality of life in terms of weight loss.

Setting: Radiotherapy Department, Nishtar Hospital Multan.

Material and Methods: Fifty patients of breast cancer were enrolled randomly in two groups. Group-A patients were given 3 gram dose of Biobran MGN-3 per day one week before and one week after chemotherapy. Group-B patient were given chemotherapy alone. Total six cycles of chemotherapy were given. No multivitamin orfood supplements were given during this study.

Chemotherapy induced side effects (tiredness, anorexia, and vomiting, hair loss) were assessed by questionnaire to the patients before start of each cycle. Weight was checked before each cycle to assess weight gain or loss. White blood cells were checked by complete blood count just before and one week after chemotherapy.

Results: Between six months, 50 patients were enrolled in Radiotherapy Department, Nishtar Hospital Multan. There was asignificant reduction in tiredness and anorexia in group-A patients. 20 (80%) patients of group-A felt increase intheirdiet and notiredness without any appetizeror multivitamin. But group-B patients demanded for appetizer due to severe anorexia after chemotherapy except 3 (12%) patients who didn't use any appetizer or food supplement. In group-A, 15 (60%) patients didnt need any anti-emetic as compared to group-B all patient (100%) experienced severe nausea during and after chemotherapy. Group-A patients experienced less hairfall 7 (28%) patients as compared to other group which is 25 (100%) patients.

Conclusions: The study showed that, by helping to optimize the immune system, Biobran MGN-3 can not only help maximize treatment success, but also minimize treatment side effects and improve quality of life during treatment and in recovery.


Amoindrissement des effets secondaires de la chimiothérapie chez les patientes atteintes du cancer du sein. 


Effekt der Abschwächung der Nebenwirkungen der Chemotherapie bei Patientinnen mit Brustkrebs. 

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

  • Mamdooh Ghoneum, Nariman K. Badr El-Din, Salma M. Abdel Fattah and Lucilene Tolentino, (edited by Chris Gutch PhD.), 2012

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.

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                                                                                                                                                          PEER REVIEWED

  • Surina Zheng, Shunsuke Sugita, Shizuka Hirai, Yukari Egashira, (edited by Chris Gutch PhD.), 2012

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- κB (NF- κB), 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 κB kinase (I κB) degradation induced by GaIN, and this was associated with the inhibition of NF κB 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- κB,NK phosphorylation and CD14 expression.

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

  • Dana Cholujova, Jana Jakubikova, Brarnislav Czako, Michaela Marisova, Luba Hunakova, Jozef Duraj, Martin Mistrik, Jan Sedlak, (edited by Chris Gutch PhD.), 2012

Abstract: Dendritic cells (DCs) and natural killer (NK) cells are central components of innate immunity for controlling tumor growth. The therapeutic effects of certain anti-myeloma drugs are partially mediated by targeting the innate immune  response. In addition, novel types of natural compounds have been developed that efficiently modulate the activity of both the cellular and humoral compartments of immunity. MGN-3 is known as an activator of natural killer cells, inducer of apoptosis and cytokine production, and modulator of dendritic cell maturation and differentiation in vitro. We have performed a randomized, placebo-controlled study to examine the effects of MGN-3 on innate immune system parameters in 48 multiple myeloma patients. We performed immunophenotypic analysis of peripheral blood samples, determined NK cell activity, and assessed the cytokine profiles of plasma before and during 3 months of treatment. The results demonstrate a clear increase in NK activity in MGN-3-treated patients compared to the placebo group, an increased level of myeloid DCs in peripheral blood, and augmented concentrations of T helper cell type 1-related cytokines.

The present study suggests that MGN-3 may represent an immunologically relevant product for activating innate immunity in multiple myeloma patients and warrants further testing to demonstrate clinical efficacy.

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

  • K. H. Ali, A. B. Melillo, S. M. Leonard, D. Asthana, Judi M. Woolger, A. H. Wolfson, H. R. McDaniel, J. E. Lewis, (edited by Chris Gutch PhD.), 2012

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.

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

  • Angela J. Henderson, Cadie A. Ollila, Ajay Kumar, Erica C. Borresen, Komal Raina, Rajesh Agarwal and Elizabeth P. Ryan, (edited by Chris Gutch PhD.), 2012

Abstract: Emerging evidence suggests that dietary rice bran may exert beneficial effects against several types of cancer, such as breast, lung, liver, and colorectal cancer. The chemopreventive potential has been related to the bioactive phytochemrcals present in the bran portion of the rice such as ferulic acid, tricin,B-sitosterol, y-oryzanol, tocotrienols/tocopherols, and phytic acid. Studies have shown that the anticancer effects of the rice bran-derived bioactive components are mediated through their ability to induce apoptosis, inhibit cell proliferation, and alter cell cycle progression in malignant cells. Rice bran bioactive components protect against tissue damage through the scavenging of free radicals and the blocking of chronic inflammatory responses. Rice bran phytochemicals have also been shovvn to activate anticancer immune responses as vvell as affecting the colonic tumor microenvironrnent in favor of enhanced colorectal cancer chemopreventron. This is accomplished through the modulation of gut microflora communities and the regulation of carcinogenemetabolizing enzymes. In addition, the low cost of rice production and the accessibility of rice bran make it an appealing candidate for global dietary chemoprevention. Therefore, the establishment of dietary rice bran as a practical food-derived chemopreventive agent has the potential to have a significant impact on cancer prevention for the global population. 

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

  • S. Zheng, H. Sanada, H. Dohi, S. Hirai and Y. Egashira, (edited by Chris Gutch PhD.), 2012

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.

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

  • M. Ghoneum, S. Gollapudi, (edited by Chris Gutch PhD.), 2011

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.

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

  • Dr. Tran Thi Minh Phuong, (edited by Chris Gutch PhD.), 2011

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.

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

  • M. Ghoneum and S. Agrawal, (edited by Chris Gutch PhD.), 2011

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-lβ}, IL-6, IL-10, TNF-α, 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.

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

                                                                                                                                PEER REVIEWED

  • 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, (edited by Chris Gutch PhD.), 2010

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 usefull at the treatment of hepatocellular carcinoma and warrants farther investigation in multiple clinical trials.