Journal of Cancer Research Updates, 2, 1-9
Anticancer Research, 34, 81-8
ドイツとスペイン大学病院を中心としたグループが小児癌の神経芽細胞腫（最近は神経芽腫と呼ぶ）の治療において米ぬかアラビノキシランはin vitroおよびin vivoで神経芽細胞腫に対するNK細胞の細胞傷害活性を刺激する事を確認しました。
Cytotherapy. 2015 May;17(5):601-12. doi: 10.1016/j.jcyt.2014.11.001. Epub 2014 Dec 23.
International Journal of Immunopathology and Pharmacology Vol. 27, no.4, 523-530(2014)
Clin Case Rep Rev, Vol. 1 (10), 235-238
Integrative Cancer Therapies April-June 2016: 1–9
Clinical Case Reports and Reviews Volume 2(6): 456-459
International Journal of Immunopathology and Pharmacology 1–7
Integr Cancer Ther. 2018 Jun;17(2):165-178. doi: 10.1177/1534735417735379. Epub 2017 Oct 17.
Case Reports of Cancer Patients with Hepatic Metastases Treated
by Standardized Plant Immunomodulatory Preparations
Abstract: Background: Metastatic hepatocellular carcinoma often has a multifocal tumor pattern with markedly depressed hepatic function. Hepatic resection in many cases results in no long-term benefit. After a chemotherapy hepatic tumors rarely disappear completely and the duration of responses is short. In 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 lectins (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/BiobranR 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.
Modified Arabinoxylan from Rice Bran, MGN-3/Biobran, Sensitizes Metastatic Breast Cancer Cells to Paclitaxel In Vitro
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. 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. 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. Our data demonstrate that MGN-3 is an effective chemosensitizer and may represent a novel adjuvant for the treatment of metastatic breast cancer.
Biobran MGN-3: Effect of reducing side effects of chemotherapy in breast cancer patients
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.
Arabinoxylan rice bran (MGN-3/Biobran) enhances natural killer cell-mediated cytotoxicity against neuroblastoma, in vitro and in vivo
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.
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.
MGN-3/Biobran stimulation of NK cells induced a higher expression of the activation-associated 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.
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.
Mgn-3/biobran enhances generation of cytotoxic CD8+ T cells via upregulation of dec-205 expression on dendritic cells.
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 α and β. 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.
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
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.
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 mistletoe lectins (ML) and Arabinoxylan in MGN-3 were compared using healthy volunteers.
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.
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.
Chemopreventive Activity of MGN-3/Biobran Against Chemical Induction of Glandular Stomach Carcinogenesis in Rats and Its Apoptotic Effect in Gastric Cancer CellsAbstract
In the current study, we investigated the chemopreventive activity of arabinoxylan rice bran, MGN-3/Biobran, against chemical induction of glandular stomach carcinogenesis in rats. Gastric cancer was induced by carcinogen methylnitronitrosoguanidine (MNNG), and rats received MNNG alone or MNNG plus Biobran (40 mg/kg body weight) for a total of 8 months. Averaged results from 2 separate readings showed that exposure to MNNG plus Biobran caused gastric dysplasia and cancer (adenocarcinoma) in 4.5/12 rats (9/24 readings, 37.5%), with 3.5/12 rats (7/24 readings, 29.2%) showing dysplasia and 1/12 rats (8.3%) developing adenocarcinoma. In contrast, in rats treated with MNNG alone, 8/10 (80%) developed dysplasia and adenocarcinoma, with 6/10 rats (60%) showing dysplasia and 2/10 rats (20%) developing adenocarcinoma. The effect of combining both agents was also associated with significant suppression of the expression of the tumor marker Ki-67 and remarkable induction in the apoptotic gastric cancer cells via mitochondrial-dependent pathway as indicated by the upregulation in p53 expression, Bax expression, downregulation in Bcl-2 expression, an increase in Bax/Bcl-2 ratio, and an activation of caspase-3. In addition, Biobran treatment induced cell-cycle arrest in the subG1 phase, where the hypodiploid cell population was markedly increased. Moreover, Biobran treatment protected rats against MNNG-induced significant decrease in lymphocyte levels. We conclude that Biobran provides protection against chemical induction of glandular stomach carcinogenesis in rats and may be useful for the treatment of human patients with gastric cancer.
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
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.
Arabinoxylan rice bran (Biobran) suppresses the viremia level in patients with chronic HCV infection: A randomized trial.
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).
Evidence-Based Review of BioBran/MGN-3 Arabinoxylan Compound as a Complementary Therapy for Conventional Cancer Treatment.
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.
To comprehensively review the available evidence on the effects and efficacies of MGN-3 as a complementary therapy for conventional cancer treatment.
Systematic search of journal databases and gray literature for primary studies reporting the effects of MGN-3 on cancer and cancer treatment.
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.
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.