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

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

HER2/neu protein expression and fine needle breast aspiration from Argentinean patients with non-palpable breast lesions

The objective of this pilot project was to investigate whether the breast fine needle aspiration (FNA) technique is a useful tool for determining the increased risk of breast cancer in patients with non-palpable breast lesions. FNA is a minimally invasive technique that isolates mammary epithelial cells from breast cells in the suspicious region. In this study, two FNA samples were collected from 12 patients. The level of HER2/neu expression at the mRNA level (in serum) was measured in each patient. As gene amplification is characteristic of cancer cells and may assist in diagnosis and prognostic assessment, it is crucial that gene amplification of HER2/neu in patients with non-palpable breast lesions is compared to breast biopsy results. In serum, the level of HER2/neu was determined by ELISA assay. Gene amplification was determined by PCR and confirmed by IHC employing monoclonal ERRB2 in the FNA sample. The results indicate that FNA has a good correlation with breast biopsy. FNA combined with mammographic imaging is a strong tool for determining favorable treatment options for patients.Fil: Domínguez, Wendy Gabriela. Texas A&M University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiarida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiarida; ArgentinaFil: Nardi, Héctor. Hospital Interzonal Dr José Penna. Departamento de Ginecología. Bahía Blanca; ArgentinaFil: Montero, Héctor. Hospital Español. Departamento de Ginecología; ArgentinaFil: Vincent, Esteban. Hospital de la Asociación Médica de Bahía Blanca. Departamento de Ginecología. Bahía Blanca; ArgentinaFil: Corte, María Marta. Laboratorio de Patología. Bahía Blanca; 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 Semiarida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiarida; 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

Genes Related to Suppression of Malignant Phenotype Induced by Maitake D-Fraction in Breast Cancer Cells

ABSTRACT It is already known that the Maitake (D-Fraction) mushroom is involved in stimulating the immune system and activating certain cells that attack cancer, including macrophages, T-cells, and natural killer cells. According to the U.S. National Cancer Institute, polysaccharide complexes present in Maitake mushrooms appear to have significant anticancer activity. However, the exact molecular mechanism of the Maitake antitumoral effect is still unclear. Previously, we have reported that Maitake (D-Fraction) induces apoptosis in breast cancer cells by activation of BCL2-antagonist/killer 1 (BAK1) gene expression. At the present work, we are identifying which genes are responsible for the suppression of the tumoral phenotype mechanism induced by Maitake (D-Fraction) in breast cancer cells. Human breast cancer MCF-7 cells were treated with and without increased concentrations of Maitake D-Fraction (36, 91, 183, 367 lg/mL) for 24 h. Total RNA were isolated and cDNA microarrays were hybridized containing 25,000 human genes. Employing the cDNA microarray analysis, we found that Maitake D-Fraction modified the expression of 4068 genes (2420 were upmodulated and 1648 were downmodulated) in MCF-7 breast cancer cells in a dose-dependent manner during 24 h of treatment. The present data shows that Maitake D-Fraction suppresses the breast tumoral phenotype through a putative molecular mechanism modifying the expression of certain genes (such as IGFBP-7, ITGA2, ICAM3, SOD2, CAV-1, Cul-3, NRF2, Cycline E, ST7, and SPARC) that are involved in apoptosis stimulation, inhibition of cell growth and proliferation, cell cycle arrest, blocking migration and metastasis of tumoral cells, and inducing multidrug sensitivity. Altogether, these results suggest that Maitake D-Fraction could be a potential new target for breast cancer chemoprevention and treatment

Serological levels of mutated p53 protein are highly detected at early stages in breast cancer patients

The aim of this study was to compare the sensitivity of the serological level of anti-p53 antibodies in breast cancer patients and to correlate its expression level with patient age, histological stage and grade of tumor differentiation. Total p53 protein expression (mutant and wild-type) was also determined in the breast cancer tissues using immunohistochemistry (IHC). The serological levels of mutant p53 expression were found to be age-dependent, reaching the highest level at 50 years of age. Faint or low detection was observed in patients ≤30 years of age. Anti-p53-antibodies were detected in patients ≤40 and ≥61 years of age. The serological levels of mutant p53 protein were highly detected in all stages of breast cancer, including the early stages. However, anti-p53 antibodies reached a high level of detection only in stage III breast carcinomas. No expression was found in patients with benign breast disease. The detection of p53 mutations was dependent on the grade of tumor differentiation, achieving the highest level in the poorly differentiated breast carcinomas. Results from IHC were highly correlated with serological p53 mutational analysis. Our findings indicate that mutant p53 in serum is a promising novel parameter for the evaluation of cellular biology and the prognosis of breast cancer from its early stages using blood samples. Anti-p53 antibodies were demonstrated to be less sensitive in this study. It is also possible to use the expression of mutant p53 protein as a molecular marker to differentiate benign breast disease from breast carcinoma prior to surgery.Fil: Balogh, Gabriela Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiarida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiarida; ArgentinaFil: Mailo, Daniel. No especifíca;Fil: Nardi, Héctor. No especifíca;Fil: Corte, María Marta. No especifíca;Fil: Vincent, Esteban. No especifíca;Fil: Barutta, Elena. No especifíca;Fil: Lizarraga, Guillermo. No especifíca;Fil: Lizarraga, Pablo. No especifíca;Fil: Montero, Héctor. No especifíca;Fil: Gentili, Roberto. No especifíca;Fil: Mordoh, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; 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

Correction to: Two years later: Is the SARS-CoV-2 pandemic still having an impact on emergency surgery? An international cross-sectional survey among WSES members

Background: The SARS-CoV-2 pandemic is still ongoing and a major challenge for health care services worldwide. In the first WSES COVID-19 emergency surgery survey, a strong negative impact on emergency surgery (ES) had been described already early in the pandemic situation. However, the knowledge is limited about current effects of the pandemic on patient flow through emergency rooms, daily routine and decision making in ES as well as their changes over time during the last two pandemic years. This second WSES COVID-19 emergency surgery survey investigates the impact of the SARS-CoV-2 pandemic on ES during the course of the pandemic. Methods: A web survey had been distributed to medical specialists in ES during a four-week period from January 2022, investigating the impact of the pandemic on patients and septic diseases both requiring ES, structural problems due to the pandemic and time-to-intervention in ES routine. Results: 367 collaborators from 59 countries responded to the survey. The majority indicated that the pandemic still significantly impacts on treatment and outcome of surgical emergency patients (83.1% and 78.5%, respectively). As reasons, the collaborators reported decreased case load in ES (44.7%), but patients presenting with more prolonged and severe diseases, especially concerning perforated appendicitis (62.1%) and diverticulitis (57.5%). Otherwise, approximately 50% of the participants still observe a delay in time-to-intervention in ES compared with the situation before the pandemic. Relevant causes leading to enlarged time-to-intervention in ES during the pandemic are persistent problems with in-hospital logistics, lacks in medical staff as well as operating room and intensive care capacities during the pandemic. This leads not only to the need for triage or transferring of ES patients to other hospitals, reported by 64.0% and 48.8% of the collaborators, respectively, but also to paradigm shifts in treatment modalities to non-operative approaches reported by 67.3% of the participants, especially in uncomplicated appendicitis, cholecystitis and multiple-recurrent diverticulitis. Conclusions: The SARS-CoV-2 pandemic still significantly impacts on care and outcome of patients in ES. Well-known problems with in-hospital logistics are not sufficiently resolved by now; however, medical staff shortages and reduced capacities have been dramatically aggravated over last two pandemic years

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries