Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
A Randomized, Controlled, Phase Ii Clinical Trial of Β-D-Mannuronic Acid (M2000) in Pre-Surgical Breast Cancer Patients at Early Stage (T1-T2) Publisher Pubmed



Kashefi S1 ; Omranipour R2, 3 ; Mahmoodzadeh H3 ; Ahmadi H2 ; Alikhassi A4 ; Hosseini M5 ; Cuzzocrea S6 ; Rehm BHA7 ; Matsuo H8 ; Mirshafiey A1, 9
Authors
Show Affiliations
Authors Affiliations
  1. 1. Department of Immunology, School of Public Health, Tehran University of Medical Science, Tehran, Iran
  2. 2. Breast Disease Research Centre (BDRC), Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Surgical Oncology, Tehran University of Medical Science, Tehran, Iran
  4. 4. Department of Radiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
  7. 7. Centre for Cell Factories and Biopolymers, Griffith Institute for Drug Discovery, Griffith University, Nathan, QLD, Australia
  8. 8. National Hospital Organization, Nagasaki National Hospital, Nagasaki, Japan
  9. 9. Research Centre for immunodeficiency, Children's Medical Centre, Tehran University of Medical Sciences, Tehran, Iran

Source: Clinical and Experimental Pharmacology and Physiology Published:2019


Abstract

Following the potent efficacy of β-D-Mannuronic acid in a breast cancer murine model, we evaluated the efficacy of this novel non-steroidal anti-inflammatory drug in breast cancer patients in the present clinical trial. The study was an 8-week randomized, controlled, phase II clinical trial (IRCT: 2017012213739N7 (in 48 pre-surgical breast cancer patients. Patients who had breast cancer at early stage, with invasive ductal carcinoma, were placed on a waiting-list for surgery and were allocated to the study. β-D-Mannuronic was administrated at a dose of two capsules (1000 mg/d) orally during a period of 8 weeks. The end point of this study was when the patients were admitted for surgery. Moreover, the patients' well-being status was followed up on for safety. There were no statistically significant differences between treatment and non-treatment groups at baseline. β-D-Mannuronic acid therapy, from 20 patients, showed that in one patient (5%) tumour size was decreased; in five patients (25%) tumour growth was stopped; and in 14 patients (70%) the growth rate in the treatment group did not show significant change, compared to the non-treatment group. Evaluation of two tumour markers (carcinoembryonic antigen and cancer antigen 15-3) showed that there was no significant difference between before and after treatment. Although the use of some non-steroidal anti-inflammatory drugs in a long time period has shown a prophylactic effect in breast cancer, their therapeutic efficacy in a short time period is unknown, whereas treatment with β-D-Mannuronic acid during 8 weeks could show 30% therapeutic effects in pre-surgical breast cancer patients. © 2019 John Wiley & Sons Australia, Ltd
Related Docs
View other Related Docs
1. Targeting of Crosstalk Between Tumor and Tumor Microenvironment by Β-D Mannuronic Acid (M2000) in Murine Breast Cancer Model, Cancer Medicine (2017)
2. The Anti-Tumoral Effect of Β-D-Mannuronic Acid (M2000) As a Novel Nsaid on Treg Cells Frequency and Mmp-2, Mmp-9, Ccl22 and Tgfβ1 Gene Expression in Pre-Surgical Breast Cancer Patients, Iranian Journal of Allergy# Asthma and Immunology (2019)
3. Influence of Β-D-Mannuronic Acid, As a New Member of Non-Steroidal An-Ti-Inflammatory Drugs Family, on the Expression Pattern of Chemokines and Their Receptors in Rheumatoid Arthritis, Current Drug Discovery Technologies (2021)
4. A Phase I/Ii Randomized, Controlled, Clinical Trial for Assessment of the Efficacy and Safety of Β-D-Mannuronic Acid in Rheumatoid Arthritis Patients, Inflammopharmacology (2018)
5. The Role of Β-D-Mannuronic Acid, As a New Non-Steroidal Anti-Inflammatory Drug on Expression of Mir-146A, Irak1, Traf6, Nf-Κb and Pro-Inflammatory Cytokines Following a Clinical Trial in Rheumatoid Arthritis Patients, Immunopharmacology and Immunotoxicology (2020)
6. International Multicenter Randomized, Placebo-Controlled Phase Iii Clinical Trial of Β-D-Mannuronic Acid in Rheumatoid Arthritis Patients, Inflammopharmacology (2019)
7. Β-D-Mannuronic Acid (M2000) As a Landmark in Pharmacology, Current Drug Discovery Technologies (2021)
8. Immunopharmacological Effect of Β-D-Mannuronic Acid (M2000), As a New Immunosuppressive Drug, on Gene Expression of Mir-155 and Its Target Molecules (Socs1, Ship1) in a Clinical Trial on Rheumatoid Arthritis Patients, Drug Development Research (2020)
Experts (# of related papers)
View all Related Experts
Mahdi Mahmoudi (10)
Ahmad Reza Jamshidi (9)
Other Related Docs
9. A Controlled, Randomized Phase Ii Clinical Trial for Efficacy and Safety Evaluation of Mannuronic Acid in Secondary Progressive Form of Multiple Sclerosis, International Journal of Neuroscience (2022)
10. Anti-Diabetic Effect of Β-D-Mannuronic Acid (M2000) As a Novel Nsaid With Immunosuppressive Property on Insulin Production, Blood Glucose, and Inflammatory Markers in the Experimental Diabetes Model, Archives of Physiology and Biochemistry (2019)
11. Modification of Sexual Hormones in Rheumatoid Arthritis Patients by M2000 (Β-D-Mannuronic Acid) As a Novel Nsaid With Immunosuppressive Property, Endocrine# Metabolic and Immune Disorders - Drug Targets (2018)
12. The Oral Administration Effect of Drug Mannuronic Acid (M2000) on Gene Expression of Matrix and Tissue Inhibitor of Metalloproteinases in Rheumatoid Arthritis Patients, Current Drug Discovery Technologies (2020)
13. Effect of Β-D-Mannuronic Acid (M2000) on Oxidative Stress Enzymes’ Gene Using Healthy Donor Peripheral Blood Mononuclear Cells for Evaluating the Anti-Aging Property, Current Drug Discovery Technologies (2019)
14. The Effects of Mannuronic Acid on Il-1Β, Il-17A, Stat1, and Stat3 Gene Expressions and Tlr2 and Tlr4 Molecules in Multiple Sclerosis, Journal of Clinical Pharmacology (2022)
15. Evaluating Mannuronic Acid Effect on Gene Expression Profile of Inflammatory Mediators in Rheumatoid Arthritis Patients, Iranian Journal of Allergy# Asthma and Immunology (2022)
16. The Potent Inhibitory Effect of Β-D-Mannuronic Acid (M2000) As a Novel Nsaid With Immunosuppressive Property on Anti-Cyclic Citrullinated Peptide Antibodies, Rheumatoid Factor and Antidsdna Antibodies in Patients With Rheumatoid Arthritis, Current Drug Discovery Technologies (2017)
17. Cardioprotective Effect of Β-D-Mannuronic Acid (M2000) As a Novel Nsaid on Gene Expression of Oxldl Scavenger Receptors in the Experimental Diabetic Model, Immunopharmacology and Immunotoxicology (2018)
18. The Effects of Β-D-Mannuronic Acid (M2000), As a Novel Nsaid, on Cox1 and Cox2 Activities and Gene Expression in Ankylosing Spondylitis Patients and the Murine Monocyte/Macrophage, J774 Cell Line, Inflammopharmacology (2018)
19. Anti‐Inflammatory and Anti‐Tumor Effects of Α-L-Guluronic Acid (G2013) on Cancer-Related Inflammation in a Murine Breast Cancer Model, Biomedicine and Pharmacotherapy (2018)
20. Effects of Β-D-Mannuronic Acid, As a Novel Non-Steroidal Anti-Inflammatory Medication Within Immunosuppressive Properties, on Il17, Rorγt, Il4 and Gata3 Gene Expressions in Rheumatoid Arthritis Patients, Drug Design# Development and Therapy (2017)
21. Immunotherapeutic Effects of Β-D Mannuronic Acid on Il-4, Gata3, Il-17 and Rorc Gene Expression in the Pbmc of Patients With Inflammatory Bowel Diseases, Iranian Journal of Allergy# Asthma and Immunology (2018)
22. Effects of Mannuronic Acid (M2000) on Gene Expression Profile of Signal Transducer and Activator of Transcription Proteins (Stats) in Rheumatoid Arthritis Patients, Reumatismo (2020)
23. Anti-Angiogenesis Effect of Β-D-Mannuronic Acid (M2000) As a Novel Nsaid With Immunosuppressive Properties Under Experimental Model, Clinical and Experimental Pharmacology and Physiology (2018)
24. Mannuronic Acid in Low-Risk and Intermediate-1-Risk Myelodysplastic Syndromes, Journal of Clinical Pharmacology (2020)
25. Targeting of Circulating Th17 Cells by Β-D-Mannuronic Acid (M2000) As a Novel Medication in Patients With Rheumatoid Arthritis, Inflammopharmacology (2018)
26. Β-D-Mannuronic Acid (M2000) and Inflammatory Cytokines in Covid-19; an in Vitro Study, Iranian Journal of Allergy# Asthma and Immunology (2022)
27. Oral Administration Effects of Β-D-Mannuronic Acid (M2000) on Th17 and Regulatory T Cells in Patients With Ankylosing Spondylitis, Biomedicine and Pharmacotherapy (2018)
28. Hematological Improvement of Patients With Active Rheumatoid Arthritis by Β-D-Mannuronic Acid (M2000) As a Novel Nsaid With Immunosuppressive Property, Iranian Journal of Allergy# Asthma and Immunology (2017)
29. Introduction of Β-D-Mannuronic Acid (M2000) As a Novel Nsaid With Immunosuppressive Property Based on Cox-1/Cox-2 Activity and Gene Expression, Pharmacological Reports (2017)
30. Efficacy of Β-D-Mannuronic Acid [M2000] on the Pro-Apoptotic Process and Inflammatory-Related Molecules Nfҡb, Il-8 and Cd49d Using Healthy Donor Pbmc, Current Drug Discovery Technologies (2020)
31. Evaluation of the Effect of Mannuronic Acid As a Novel Nsaid With Immunosuppressive Properties on Expression of Socs1, Socs3, Ship1, and Traf6 Genes and Serum Levels of Il-6 and Tnf-Α in Patients With Multiple Sclerosis, Journal of Clinical Pharmacology (2021)
32. The Inhibitory Role of M2000 (Β-D-Mannuronic Acid) on Expression of Toll-Like Receptor 2 and 4 in Ht29 Cell Line, Recent Patents on Inflammation and Allergy Drug Discovery (2019)
33. Pharmacological Effects of Β-D-Mannuronic Acid (M2000) on Mir-146A, Irak1, Traf6 and Nf-Κb Gene Expression, As Target Molecules in Inflammatory Reactions, Pharmacological Reports (2017)
34. The Potent Suppressive Effect of Β-D-Mannuronic Acid (M2000) on Molecular Expression of the Tlr/Nf-Kb Signaling Pathway in Ankylosing Spondylitis Patients, International Immunopharmacology (2017)
35. Immunomodulatory Effects of M2000 (Β-D-Mannuronic Acid) on Tnf-Α, Il-17 and Foxp3 Gene Expression in Patients With Inflammatory Bowel Disease, International Immunopharmacology (2017)
36. The Biology of Β-D-Mannuronic Acid (M2000) on Human Dendritic Cell Based on Microrna-155 and Microrna-221, Current Drug Discovery Technologies (2017)
37. The Situation of Chemokine Ligands and Receptors Gene Expression, Following the Oral Administration of Drug Mannuronic Acid in Rheumatoid Arthritis Patients, Recent Patents on Inflammation and Allergy Drug Discovery (2020)
38. Effects of M2000 (D -Mannuronic Acid) on Learning, Memory Retrieval, and Associated Determinants in a Rat Model of Alzheimer's Disease, American Journal of Alzheimer's Disease and other Dementias (2017)
39. Anti-Tumor Effect of M2000 (Β-D-Mannuronic Acid) on the Expression of Inflammatory Molecules in the Prostate Cancer Cell, Immunopharmacology and Immunotoxicology (2021)
40. Evaluation of Cell Adhesion Molecules (Lfa-1 and L-Selectin) in Ankylosing Spondylitis Patients After Treatment With ß-D-Mannuronic Acid (M2000), Indian Journal of Medical Research (2023)
41. Clinical Improvement of Diabetes Mellitus Type 1 by Β-D-Mannuronic Acid (M2000) in a Breast Cancer Patient - As a Case Report, Clinical Diabetology (2019)
42. Preclinical Assessment of Β - D -Mannuronic Acid (M2000) As a Non-Steroidal Anti-Inflammatory Drug, Immunopharmacology and Immunotoxicology (2015)
43. The Immunobiology of Myeloid-Derived Suppressor Cells in Cancer, Tumor Biology (2016)
44. Preclinical and Pharmacotoxicology Evaluation of Α-L-Guluronic Acid (G2013) As a Non-Steroidal Anti-Inflammatory Drug With Immunomodulatory Property, Immunopharmacology and Immunotoxicology (2017)
45. M2000 (Β-D-Mannuronic Acid) As a Novel Antagonist for Blocking the Tlr2 and Tlr4 Downstream Signalling Pathway, Scandinavian Journal of Immunology (2017)
46. An in Vitro Assessment for Evaluating the Efficiency of Β-D-Mannuronic Acid (M2000) in Myelodysplastic Syndrome, Journal of Cellular Physiology (2019)
47. Regulatory T Cells in Breast Cancer As a Potent Anti-Cancer Therapeutic Target, International Immunopharmacology (2020)
48. Dysregulated Mirnas Network in the Critical Covid-19: An Important Clue for Uncontrolled Immunothrombosis/Thromboinflammation, International Immunopharmacology (2022)
49. Evaluation of the Efficacy and Safety of Β-D-Mannuronic Acid in Patients With Ankylosing Spondylitis: A 12-Week Randomized, Placebo-Controlled, Phase I/Ii Clinical Trial, International Immunopharmacology (2018)
50. The Effect of Β-D-Mannuronic Acid in Animal Model of Epilepsy, Natural Product Communications (2020)