Immunotherapeutic and Preventive Role of Purified Extract Rich in Beta-Glucans Derived from D-Fraction of Grifola frondosa Mushroom in Experimental Mice Biomodel of Mammary Carcinogenesis

The overall vision of the modern science needs to change to a revalorization of the natural compounds and their beneficial effects on human diseases, such as cancer. Medicinal mushrooms have been used since thousands of years due to its healing properties. Maitake (Grifola frondosa) is presented as one of the most interesting medicinal mushrooms that have been studied. Until now, Maitake D-Fraction may have anticarcinogenic activity, preventing oncogenesis and metastasis in certain tumor types. However, the exact molecular mechanism by which D-Fraction acts are yet unknown. The results shown in this chapter suggest that Maitake D-Fraction Pro4X, administered intraperitoneally, prevents significantly the development of mammary tumorigenesis, increases survival, and reduces the process of angiogenesis in BALBc mice. Although yet to determine the active component of the extract and the molecular mechanism by which it operates in the breast carcinogenesis process. The socioeconomic impact of this research project could be important, considering that in Argentina similar studies using natural compounds derived from medicinal mushrooms for cancer therapy have not yet been performed. The beneficial effects of Maitake, if proven, could be useful for the treatment of cancer patients who are undergoing chemotherapy or radiation or for breast cancer prevention in high-risk population

Comparative Effect of Maitake Pro4x with Chemotherapy Breast Cancer Treatment

Conventional treatments for breast cancer involve surgery followed by radiation and hormonal therapy and/or chemotherapy. Some of these treatments have toxic side effects. Because drugs used in chemotherapy affect both cancer and normal cells to varying degrees, researchers are currently developing targeted drugs that only attack cancer cells without affecting normal cells. One approach to this is to found compounds that are more selective and specific, destroying only tumour cells and prevent metastases without harming normal cells. For thousands of years, medicinal mushrooms have been used because of their healing properties. Maitake (Grifola frondosa) is one of the most promising edible and medicinal mushroom, acting promoting the immune system against the tumorigenesis process. Methods: In the in vitro studies, we measured and compared the effect of Maitake Pro4X or Chemotherapy on LM3 Breast Tumour Cells death. Increased concentrations and different time of treatments were employed. In the in vivo studies, we employed breast tumour bearing female BALBc mice 6-8 weeks old, to assayed the effect of Maitake Pro4X with or without chemotherapy measuring the tumour volume, mortality, relative survival and size of tumour necrosis area after treatment. Results: After 5 weeks of treatment in tumour-bearing BALBc mice, we observed that Maitake Pro4X significantly increased the overall survival of animals and reduced the malignancy of breast tumours. We also found that Maitake Pro4X, as chemotherapy, induce cell-death in a dose and time dependent form. Conclusion: The beneficial effects of Maitake D-Fraction Pro4X, if supported by further evidence could be useful for the treatment of cancer patients to reduce the adverse effects of the conventional chemotherapy treatment.Fil: Aguilera Braico, Diego Máximo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Ciencias de la Salud; ArgentinaFil: Roldán Deamicis, Agustina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Brie, Belen. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Balogh, Gabriela Andrea. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentin

Molecular Mechanism Induced by Beta-Glucans from Maitake to Recover T Cell-Subpopulations during Immunosuppression

Breast cancer is the most frequent neoplasia in the world and one of the main causes of death among women. Some of the conventional treatments for cancer are chemotherapy or radiotherapy, knowing that both generate very toxic side effects since they usually affect all cells in active division (healthy or tumoral cells). Therefore, specific treatments are necessary, with therapies aimed at the molecular characteristics of the tumor and its microenvironment. An approach to this could be the search for natural compounds with immunopotentiating capacity and selective toxicity on tumor cells. Recently, immunomodulatory and antitumor activities have been discovered in various fungi. Among them, β-glucans of D-Fraction of Grifola frondosa (Maitake) can generate innate and adaptive immune responses, exerting antitumor effects. The reported therapeutic benefits of treatment of breast tumorigenesis with D-Fraction of Maitake require to deepen pharmacological and toxicological studies, in order to guarantee innocuousness and efficacy in the administration to a patient. Therefore, this chapter aimed to elucidate toxicological, pharmacodynamic, and pharmacokinetic aspects of β-glucans from D-Fraction. In this way, we hope to make a significant contribution to the pharmacological knowledge of these bioactive compounds by promoting an immunotherapeutic and antitumor strategy novel agent

Maitake Pro4X has anti-cancer activity and prevents oncogenesis in BALBc mice

The understanding of the molecular mechanisms of the immune tolerance induced by the tumoral microenvironment is fundamental to prevent cancer development or to treat cancer patients using immunotherapy. Actually, there are investigations about "addressed-drugs" against cancer cells without affecting normal cells. It could be ideal to find selective and specific compounds that only recognize and destroy tumor cells without damaging the host normal cells. For thousands of years, mushrooms have been used for medicinal purposes because of their curative properties. D-Fraction, an extract of Maitake (from the edible Grifola frondosa mushroom), rich in β-glucans, exert notable effects in the immune system. Until now, some published articles suggest that Maitake D-Fraction could have anti-tumoral activity, prevent oncogenesis and metastasis in some tumor types. However, there are no clear data about Maitake D-Fraction action on breast cancer prevention and its exact molecular mechanisms are not yet elucidated. The experiments were performed employing 25 female BALBc mice that were treated with and without Maitake D-Fraction Pro4X or Maitake Standard for 15 days by daily intraperitoneal injection. After treatment period, all mice were implanted with murine tumor cells LM3 to induce mammary tumorigenesis. Animals were checked weekly and killed after 46 days of LM3 transplant; percentage of cancer prevention, rate of tumor growing, and overall survival were determined. Under dissection, the internal organs were evaluated histologically and genetically by RT-PCR. We found that 5 mg/kg per day of Maitake D-Fraction Pro4X, administered dairy during 15 days to BALBc mice was able to block more than 60% breast cancer development. However, Maitake Standard prevents oncogenesis in 26% to respect control. In this work, we found that Maitake D-Fraction Pro4X, administered to BALBc mice, prevents breast carcinogenesis, block tumor invasiveness, reduce angiogenesis, and increase overall survival.Fil: Roldan Deamicis, Agustina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Alonso, Eliana Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; ArgentinaFil: Brie, Belen. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Aguilera Braico, Diego Máximo. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Balogh, Gabriela Andrea. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentin

BRCA1 polymorphism in breast cancer patients from Argentina

Breast cancer is the most common type of cancer in females in Argentina, with an incidence rate similar to that in the USA. However, the contribution of the BRCA1 or BRCA2 mutation in breast cancer incidence has not yet been investigated in Argentina. In order to evaluate which BRCA1 polymorphisms or mutations characterize female breast cancer in Argentina, the current study enrolled 206 females with breast cancer from several hospitals from the southeast of Argentina. A buccal smear sample was obtained in duplicate from each patient and the DNA samples were processed for polymorphism analysis using the single-strand conformational polymorphism technique. The polymorphisms in BRCA1 were investigated using a combination of 15 primers to analyze exons 2, 3, 5, 20 and 11 (including the 11.1 to 11.12 regions). The BRCA1 mutations were confirmed by direct sequencing. Samples were successfully examined from 154 females and, among these, 16 mutations were identified in the BRCA1 gene representing 13.9% of the samples analyzed. One patient was identified with a polymorphism in exon 2 (0.86%), four in exon 20 (3.48%), four in exon 11.3 (3.48%), one in exon 11.7 (0.86%), two in exon 11.8 (1.74%), one in exon 11.10 (0.86%) and one in exon 11.11 (0.86%). The most prevalent alteration in BRCA1 was located in exon 11 (11 out of 16 patients; 68.75%). The objective of our next study is to evaluate the prevalence of mutations in the BRCA2 gene and analyze the BRCA1 gene in the healthy relatives of BRCA1 mutation carriers.Fil: Jaure, Omar David Argentino. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; ArgentinaFil: Alonso, Eliana Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; ArgentinaFil: Aguilera Braico, Diego Máximo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; ArgentinaFil: Nieto, Alvaro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; ArgentinaFil: Orozco, Manuela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; ArgentinaFil: Morelli, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; ArgentinaFil: Ferro, Alejandro M.. Hospital Italiano; ArgentinaFil: Barutta, Elena. Medifem; ArgentinaFil: Vincent, Esteban. Medifem; ArgentinaFil: Martínez, Domingo. Provincia de Buenos Aires. Ministerio de Salud. Hospital Municipal de Agudos Dr. Leónidas Lucero; ArgentinaFil: Martínez, Ignacio. Provincia de Buenos Aires. Ministerio de Salud. Hospital Municipal de Agudos Dr. Leónidas Lucero; ArgentinaFil: Maegli, Maria Ines. Provincia de Buenos Aires. Ministerio de Salud. Hospital Municipal de Agudos Dr. Leónidas Lucero; ArgentinaFil: Frizza, Alejandro. Medifem; ArgentinaFil: Kowalyzyn, Ruben. Clínica Viedma; ArgentinaFil: Salvadori, Marisa. Hospital Dr. Lucio Molas; ArgentinaFil: Ginestet, Paul. Provincia de Buenos Aires. Ministerio de Salud. Hospital y Maternidad Municipal Pigüé; ArgentinaFil: Gonzalez Donna, Maria L.. Hospital Italiano; ArgentinaFil: Balogh, Gabriela Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; Argentin

Inmunotherapeutic and preventive rol of purified extract reach in beta-glucans derived from D-fraction of grifola frondosa mushroom in experimental mouse biomodel of mammary carcinogenesis

The overall vision of the modern science needs to change to a revalorization of the natural compounds and their beneficial effects on human diseases, such as cancer. Medicinal mushrooms have been used since thousands of years due to its healing properties. Maitake (Grifola frondosa) is presented as one of the most interesting medicinal mushrooms that have been studied. Until now, Maitake D-Fraction may have anticarcinogenic activity, preventing oncogenesis and metastasis in certain tumor types. However, the exact molecular mechanism by which D-Fraction acts are yet unknown. The results shown in this chapter suggest that Maitake D-Fraction Pro4X, administered intraperitoneally, prevents significantly the development of mammary tumorigenesis, increases survival, and reduces the process of angiogenesis in BALBc mice. Although yet to determine the active component of the extract and the molecular mechanism by which it operates in the breast carcinogenesis process. The socioeconomic impact of this research project could be important,considering that in Argentina similar studies using natural compounds derived from medicinal mushrooms for cancer therapy have not yet been performed. The beneficial effects of Maitake, if proven, could be useful for the treatment of cancer patients who are undergoing chemotherapy or radiation or for breast cancer prevention in high-risk population.Fil: Aguilera Braico, Diego Máximo. Universidad Nacional del Sur. Departamento de Ciencias de la Salud; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Balogh, Gabriela Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Sur. Departamento de Ciencias de la Salud; Argentin

Additional file 1 of CD3Ɛ immune restorative ability induced by Maitake Pro4x in immunosupressed BALBc mice

Additional file 1: Table S1. CD3Ɛ FITC labelled cell population in lymph node and spleen from BALBc mic

Additional file 4 of CD3Ɛ immune restorative ability induced by Maitake Pro4x in immunosupressed BALBc mice

Additional file 4: Table S4. L6G FITC labelled cell population in lymph node and spleen from BALBc mice

Additional file 3 of CD3Ɛ immune restorative ability induced by Maitake Pro4x in immunosupressed BALBc mice

Additional file 3: Table S3. CD105 AF labelled cell population in lymph node and spleen from BALBc mic

Additional file 2 of CD3Ɛ immune restorative ability induced by Maitake Pro4x in immunosupressed BALBc mice

Additional file 2: Table S2. CD19 PE labelled cell population in lymph node and spleen from BALBc mic