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Research



RADIOPROTECTIVE EFFECT IN CERVICAL CANCER PANCREAS CANCER CASE EFFECTS OF MM PATIENTS ON IMMUNE INCREASING SENSITIVITY OF CHEMOTHERAPY IN BREAST CANCER INCREASING SENSITIVITY OF LEUKEMIA CELLS TO APOPTOSIS INCREASING THE INTERVENTIONAL EFFECT IN HEPATOCELLULAR CARCINOMA EFFECT ON SURVIVAL AND QUALITY OF LIFE IN PROGRESSIVE CANCER NK ACTIVITY INCREASING EFFECT REDUCING SIDE EFFECTS OF CHEMOTHERAPY IN BREAST CANCER INCREASING MACROPHAGE PHAGOCYTOSIS NK CELL ACTIVITY INCREASING EFFECT OF CANCER PATIENTS

RADIOPROTECTIVE EFFECT IN CERVICAL CANCER



Itoh Y, Mizuno M, Ikeda M, et al. A randomized, double-blind pilot trial of hydrolyzed rice bran versus placebo for radioprotective effect on acute gastroenteritis secondary to chemoradiotherapy in patients with cervical cancer. Evid Based Complement Alternat Med. 2015; 2015:947390.

In this study, the radioprotective effect of hydrolysed rice bran (HPC) in chemotherapy-induced acute gastroenteritis in the treatment of cervical cancer was investigated. This placebo-controlled double-blind study was designed to investigate the anti-colitis effects of hydrolysed rice bran in alleviating acute phase gastrointestinal side effects of chemoradiotherapy. Twenty patients (10 in the HPC group and 10 in the control group) were included in the study. Patients in the control group received the same chemoradiotherapy as those in the HPK group, but received placebo instead of the HPK. The diarrhea side effect assessment score was lower in the HPC group than in the control group, and a decrease in diarrhea symptoms was observed with oral HPK intake. In addition, no significant difference was observed in the administration of intestinal regulators and antidiarrheal agents, but the assessment score was lower in the HPC group than in the control group and diarrhea symptoms were alleviated by oral HPC use. The results show that chemoradiotherapy of hydrolysed rice bran can alleviate diarrhea, an acute phase gastrointestinal side effect.

PANCREAS CANCER CASE



Kaketani, K . A case where an immunomodulatory food was effective in conservative therapy for progressive terminal pancreatic cancer. Clin Pharmacol Ther. 2004;14:273-279.

A patient with terminal pancreatic cancer accompanied by distant metastasis, therefore unsuitable for radical surgery, has been reported to have biological defense effect, accelerate blood circulation, contain π water, which increases the transport (transporter effect) of nutrients and drugs, further reducing the effect of toxic chemotherapeutics. Rice bran was treated with arabinoxilane derivative to maintain biological functions and quality of life (QOL). As a result, satisfactory therapeutic effects such as growth and spontaneous therapeutic power in biological functions were obtained.

EFFECTS OF MM PATIENTS ON IMMUNE



Cholujova D, Jakubikova J, Czako B, Martisova M, Hunakova L, Duraj J, Mistrik M, Sedlak J. “MGN-3 Arabinoxylan Rice Bran Modulates Innate Immunity in Multiple Myeloma Patients Cancer Immunol Immunother. Mar; 62 (3): 437-45., 2013.

Dendritic cells (DCs) and Natural Killer (NK) cells are central components of innate immunity that control tumor growth. Some anti-myeloma drugs show therapeutic effect by targeting the innate immune response. In addition, novel natural compounds have been developed that effectively modulate both cellular and humoral immunity. MGN-3 is known as an activator of natural killer cells (NK), a stimulator of apoptosis and cytokine production, and a modulator of dendritic cell maturation and differentiation in vitro. We conducted a randomized, placebo-controlled study to examine the effects of MGN-3 on natural immune system parameters in 48 multiple myeloma patients. We performed immunophenotypic analysis of peripheral blood samples, determined NK cell activity, and evaluated plasma cytokine profiles for 3 months before and during treatment. The results showed a significant increase in NK activity in MGN-3 treated patients compared to the placebo group, increased myeloid dendritic cell levels in peripheral blood, and increased Type-1 T helper cell-associated cytokine concentrations. This study demonstrates that MGN-3 may be an immunology-related product that activates natural immunity in Multiple Myeloma patients and deserves further studies to demonstrate clinical efficacy.

INCREASING SENSITIVITY OF CHEMOTHERAPY IN BREAST CANCER




Gollapudi, S.V., & Ghoneum, M.H. (2008). MGN-3/Biobran, modified arabinoxylan from rice bran, sensitizes human breast cancer cells to chemotherapeutic agent, daunorubicin. Cancer detection and prevention, 32 1, 1-6 .

MGN-3 / Biobran (Bi.Bran), a modified form of arabinoxilane from rice bran, is a powerful biological response enhancer (BRM). Our previous studies have shown that MGN-3 makes human leukemia cells susceptible to death receptor [CD95] -dependent apoptosis (Ghoneum M, Gollapudi S.) MGN-3 made human T-cell leukemia cells susceptible to CD-95 death receptor-mediated apoptosis. Lett 2003; 201: 41-9). In this study, we evaluated in vitro changes caused by MGN-3 in chemosensitivity activity in human breast cancer cells (BCCs). Methods: BCCs (MCF-7 and HCC70 cells), 3 days (100) at different concentrations in the presence or absence of selected MGN-3 concentrations. –1000 μg / ml) was cultured with daunorubicin (DNR) (1x109 to 1x106 M). Cancer cell survival was determined by MTT assay; drug accumulation was determined by flow cytometry. Results: Compared to MGN-3 treated BCCs with DNR treated alone, MGN-3 increased the sensitivity of BCCs to DNR (5.5 times for MCF-7 and 2.5 times for HCC70 cells). The sensitizing effect of MGN-3 was associated with increased DNR accumulation in cancer cells. Conclusion: Our data show that MGN-3 is an effective chemosensitizer and may be a potential new adjuvant for the treatment of breast cancer.

INCREASING SENSITIVITY OF LEUKEMIA CELLS TO APOPTOSIS



Ghoneum M., Gollapudi S. Modified arabinoxylan rice bran (MGN-3 / Biobran) sensitizes human T cell leukemia cells to death receptor (CD95) -induced apoptosis. Cancer Letters. 2003; 201 (1): 41-49.

Arabinoxilane (MGN-3) obtained enzymatically from rice bran by means of an extract from Shiitake fungi is an effective biological response modifier that enhances NK cell activity and enhances the activity of conventional chemotherapeutic agents. In this study, we investigated the effect of MGN-3 on death receptor mediated apoptosis in human leukemic HUT 78 cell line. HUT 78 cells were pretreated with MGN-3 and then incubated with agonistic antibody against the 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 and mitochondrial membrane potential was measured by DIOC (6) stain using FACScan. CD95 and Bcl-2 expression was measured by flow cytometry. The results showed that MGN-3 increased apoptosis induced by anti-CD95 antibody in a dose-dependent manner. Increased cell death was associated with increased depolarization of mitochondrial membrane potential and increased activation of Caspase-3, Caspase-8 and Caspase-9. MGN-3 administration did not show an effect on the expression level of CD95 but caused down-regulation of Bcl-2. These results show that MGN-3 increases susceptibility to apoptosis mediated by death ligands of cancer cells and may be suitable for anti-cancer activities.

INCREASING THE INTERVENTIONAL EFFECT IN HEPATOCELLULAR CARCINOMA




Bang MH, Van Riep T, Thinh NT, Song Le H, Dung TT, Van Truong L, Van Don L, Ky TD, Pan D, Shaheen M, Ghoneum M. “Arabinoxylan Rice Bran (MGN-3) Enhances the Effects of Interventional Therapies for the Treatment of Hepatocellular Carcinoma: A Three-year Randomized Clinical Trial Ant, Anticancer Research. Dec; 30 (12): 5145-51., 2010.

In this study, the contribution of rice bran arabinoxilane (MGN-3) to the efficacy of interventional treatment (IT) in the treatment of hepatocellular carcinoma patients was investigated. Patients and Methods: Sixty-eight patients (stage I and II) with hepatocellular carcinoma were included in the study. Patients were randomized to receive either IT (30 patients, control group) or IT + MGN-3 (38 patients) and were randomly divided into two groups using a computer-based randomization list. Patients and researchers were prevented from knowing whether the patients in the study were in the experimental or control group. IT included transarterial fatty chemoembolization (TOCE) or a combination of TOCE and percutaneous ethanol injection (PEIT). Results: (i) 46.7% (14/30) of the control group compared to control group had lower disease recurrence 31.6% (12/38) in the IT + MGN-3 group; (ii) higher survival (35%) in the MGN-3 group after the second year than in the control group (6.7%); (iii) alpha-fetoprotein levels were not significantly different in the control group, whereas in the MGN-3 group a 38% decrease compared to baseline (p = 0.0001); and (iv) unlike the control group, there was a significant reduction in tumor volume in the MGN-3 group. When the results were analyzed according to each IT method, MGN-3 + IT subgroups responded more to treatment than IT subgroups. However, patients in the MGN-3 + TOCE + PEIT subgroup showed more reduction in AFP levels and longer survival than the MGN-3 + TOCE subgroup. Conclusion: MGN-3 may be useful in the treatment of hepatocellular carcinoma with interventional therapies and deserves further clinical studies.

EFFECT ON SURVIVAL AND QUALITY OF LIFE IN PROGRESSIVE CANCER




Takahara K, Sano K. “The Life Prolongation and QOL Improvement Effect of Rice Bran Arabinoxylan Derivative (MGN-3, BioBran) for Progressive Cancer”, Clinical Pharmacology and Therapy. 14(3):267-71., 2004.

This study was conducted to determine whether MGN-3 administration had an impact on survival and quality of life for 205 progressive and partially metastatic cancer patients at the end of the postoperative III-IV stages. MGN-3 is a rice bran arabinoxylan derivative and is known to have immunomodulation activity. Participants in this clinical trial were patients in hospitals treated with complementary alternative medications (what we call Olmayan Unconventional Therapy)) in our clinic, and anticancer drugs with fewer side effects. 205 patients hospitalized for 6 months were divided into two groups, ie 109 patients (control group) treated with our standard complementary alternative medications and 96 patients who were given MGN-3 (MGN-3 group) for one year. Natural killer-NK was measured in all patients as an indicator of variation of immunoparameters. The quality of life of the patients was also checked. Postoperative NK cell activities of the patients were low on average; however, with the administration of MGN-3, NK activity increased and survival rate increased; As the NK activity increased, the survival also increased. The above findings indicate that NK activity can be used as a pathological index of progressive cancers. Quality of life improvement was also observed in MGN-3 application.

NK ACTIVITY INCREASING EFFECT




NATURAL KILLER CELL ACTIVITY INCREASING IMPACT Ghoneum M. XIV (2): 89-99., 1998. The effect of Arabinoxilane (MGN-3) obtained by the reaction of rice bran with Shiitake fungi was investigated in human and natural killer-NK activity enhancer in vivo and in vitro. Twenty-four subjects 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 against K562 and Raji tumor cells was measured by the 51 Cr release test at 1 week, 1 month and 2 months of treatment, and the results were compared to baseline NK cell activity.

MGN-3 increased NK activity against K562 tumor cells at all concentrations used. In a dose-dependent manner, MGN-3 increased NK activity at 15 mg / kg / day, 1 month after treatment (twice the control value), while significant induction of NK activity at 30 mg / kg / day at 1 week post-treatment. three times the control value). NK cell activity continued to increase with continued use and peaked at the end of the 2nd month (at the end of treatment) (five-fold increase). Increasing the concentration to 45 mg / kg / day showed similar trends in NK activity, but values ​​were higher than 30 mg / kg / day. After discontinuation of treatment, NK activity decreased and returned to baseline (1 liter unit) after 1 month. Increased NK activity was associated with an increase in cytotoxic reactivity against the resistant Raji tumor cell line. MGN-3, administered at a dose of 45 mg / kg / day, showed a significant increase in NK cell activity (eight-fold) in the first week of use and peaked at the end of the second month (27-fold increase). Culture of peripheral blood lymphocytes (PBL) with MGN-3 for 16 hours resulted in a 1.3 to 1.5-fold increase in NK activity compared to the control value. The mechanism by which MGN-3 increases NK activity has also been investigated; In the differentiation cluster (CD) 16+ and CD56 + CD3- of MGN-3-activated NK cells compared to baseline, no change was observed, a four-fold increase in the binding capacity of NK cells to targets in the tumor cell compared to baseline, MGN- at concentrations of 25-100 μg / ml A significant increase in interferon-üretim (340-580 pg / ml) production of peripheral blood lymphocytes cultured with 3 was measured. Therefore, MGN-3; NK acts as a potent immunomodulator to increase cell activity. MGN-3 can be used as a novel biological response enhancer (BRM) with no potential therapeutic effects against cancer, with no significant side effects.

THE EFFECT OF REDUCING THE SIDE EFFECTS OF CHEMOTHERAPY IN BREAST CANCER PATIENTS




Masood AI, Sheikh R, Anwer RA. "Biobran MGN-3"; chemotherapy Prof Med J. 2013; 20: 13-16.

Purpose: To investigate the effect of Biobran (Bi.Bran) on chemotherapy-induced fatigue, anorexia, vomiting, hair loss and weight loss and quality of life

Materials and methods: 50 breast cancer patients were randomly divided into two groups. Group A patients received oral Biobran MGN-3 at a dose of 3 grams a day 1 week before and 1 week after chemotherapy. Group B patients received chemotherapy only. A total of 6 chemotherapy courses were given. Patients were not given any multivitamin or food supplements during the study. Chemotherapy-induced side effects (fatigue, anorexia, vomiting, and hair loss) were assessed by a questionnaire at the beginning of each chemotherapy cycle. Weight measurements were performed at the beginning of each chemotherapy cycle. White blood cells were measured by total blood count immediately before and 1 week after each chemotherapy.

Results: Fifty patients were enrolled in Nishtar Hospital (Multan) Radiotherapy Department within 6 months. There was a significant reduction in fatigue and anorexia in Group A patients receiving Biobran (Bi.Bran). However, except for 3 patients (12%), Group B patients requested an appetite boost due to loss of appetite due to anorexia. 15 patients (60%) of Group B patients did not feel any need for anti-emetic; all Group B patients (100%) experienced nausea after chemotherapy. The rate of hair loss in Group A patients was 28%, whereas this was seen in all Group B patients (100%).

CONCLUSIONS: This study demonstrated that Biobran helps maximize the chances of treatment by minimizing the side effects of chemotherapy and improving quality of life, as well as helping to optimize the immune system.

INCREASING MACROPHAGE PHAGOCYTOSIS




Ghoneum, M., & Matsuura, M. (2004). Augmentation of Macrophage Phagocytosis by Modified Arabinoxylan Rice Bran (MGN-3/Biobran). International Journal of Immunopathology and Pharmacology, 283–292.

Rice bran modified arabinoxylan MGN-3 / Bi.Bran has been shown to be a potent biological response modifier (BRM) that is demonstrated by stimulating different branches of the immune system such as T and B cells; however, its effect on macrophages has not yet been studied. The effects of MGN-3 on macrophage function were examined in vitro using 3 models: human macrophage cell line U937, murine macrophage cell line RAW264.7 and murine peritoneal macrophages (P-M phi). Treatment with MGN-3 resulted in increased binding and phagocytosis rates of macrophages to yeast. The effect depends on the type of macrophage and the dose of MGN-3 administered. Macrophages also improved their ability to spread after treatment with MGN-3. The results also showed that MGN-3 resulted in high cytokine production in a dose-dependent manner (1, 10,100 micrograms / ml): TNF-alpha; and IL-6. In addition, MGN-3 significantly increased nitric oxide (NO) production. These data show that MGN-3 is a potent inducer of phagocytic function with macrophage, and that MGN-3 is a useful agent in the fight against microbial infection.

NK CELL ACTIVITY INCREASING EFFECT OF CANCER PATIENTS




Ghoneum M, Brown J. NK immunorestoration of cancer patients by MGN-3, a modified arabinoxylan rice bran (study of 32 patients followed for up to 4 years) In: Klatz R, Goldman R, editors. Wheat and rice in disease prevention and health. Anti-aging medical therapeutics. III. Health Quest Publications; Marina del Rey, CA: 1999. pp. 217-226.

Patients: The study was conducted non-randomly with 32 cancer patients. Patients; prostate (10), mem (12), multiple myleoma (5) and leukemia. Patients have received conventional treatments such as surgery, chemotherapy and radiotherapy.

Material: MGN-3; An extract obtained from Shiitake mushroom and arabinoxylated enzymatically from rice bran. MGN-3 is a polysaccharide and is commercially known as Biobran (Daiwa Pharm., Co., Ltd., Tokyo, Japan).

Methods: MGN-3 was given to patients 3 grams (oral) daily for 1 month. Tumor-related antigens were measured before and at the end of treatment 1 month. NK Cell activity was measured at Week 1 of the treatment and 1 week after the end of treatment. The increase in proliferation of T and B cells in response to different mitogens was measured before treatment and 1 month after treatment.

Results: Patients had low NK cell activity before treatment. Treatment with MGN-3 resulted in a marked increase in NK cell activity in patients up to 10-fold. In addition, B cell and T cell proliferation increased with MGN-3 treatment. The mechanism of action of MGN-3 was explained by an increase in NK cell granulation followed by changes in cytokine production. It was reported that MGN-3 provides immunostimulation.







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