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2-aminoethyl Dihydrogen Phosphate as a Modulator of Proliferative and Apoptotic Effects in Breast Cancer Cell Lines

Journal of Pharmacy and Pharmacology 2021年第3期9卷 83-97页

作者： Manuela garcia Laveli da Silva laertty garcia de sousa cabral Monique Gonçalves Alves Thais deOliveira Conceição Henrique Hesse Rosa Andrea Nogueira Laiso Daniel da Conceição Rabelo Durvanei Augusto Maria development and Innovation Laboratory Butantan InstituteSao PauloSP 05503-900Brazil Faculty of Medicine University of São PauloSao PauloSP 01246-000Brazil

Background: Breast cancer is a type of cancer that affects more women throughout the world, in developing anddeveloped countries. 2-AEH2P is a phospholipid analog of cellular membrane, which makes it different from existing molecules fortheir absorption, stability and display anti-inflammatory, anti-proliferative and pro-apoptotic properties. Methods: MCF-7 humanbreast adenocarcinoma cells were treated with 2-AEH2P. The viability and adhesion cells were evaluated by MTT assay. Cell cyclephases, apoptosis, markers and mitochondrial potential were assessed by flow cytometry. Morphological ultrastructural analyzeswere performed by laser confocal microscopy. Results: MCF-7 Tumor cells acquired round shapes, lost cytoplasmic expansions,formed clusters in suspension and decreased significantly viability. There were changes in the morphology, membrane fragmentationand loss of cytoplasmic projection. The obtained concentrations for IC50% were 37.2;25.8;1.8 mM for periods of 24, 48 and 72 h,respectively. Changes in the distribution of cell population phases of the cell cycle showed an increase in fragmented DNA and anincrease in the G2/M phase. The expression β-gal showed proliferative reduction induced by 2-AEH2P. Laser confocal microscopyshowed changes in the mitochondrial membrane and alteration in distribution. Proliferative index of MCF-7 tumor cells treated with2-AEH2P decreased significantly when compared to fibroblast normal cells. The compound 2-AEH2P is a phospholipid withantiproliferative potential and apoptosis modulator.

关键词： Human Breast Adenocarcinoma MCF-7 2-AEH2P Antitumor Apoptosis Cell cycle Senescence

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Clinical Oncology Translational Study Phase-1 with Antitumor Phosphorylethanolamine(2-AEH_(2)P)in Dogs with Neoplasms

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Journal of Pharmacy and Pharmacology 2021年第5期9卷 179-196页

作者： Olivia Gonçalves de Almeida Leitão da Cunha Lucas Campos de SáRodrigues Daniel da Conceição Rabelo Rosa Andrea Nogueira Laiso Sergio Mestieri Chammas laertty garcia de sousa cabral Durvanei Augusto Maria development and Innovation Laboratory Butantan InstituteAvenue Vital Brasil1500Sao Paulo 05503-900Brazil Faculty of Veterinary Medicine and Animal Science Sao Paulo UniversitySao Paulo 01246-000Brazil Veretinary Hospital Estima Avenue Granadeiro GuimaraesTaubaté155Sao PauloBrazil Faculty of Medicine of the University of São Paulo São Paulo 01246-000Brazil

The animal has the potential to serve as a clinical model for human disease,due to striking similarities and homologies in *** clinical development of a new drug may influence its final destination,and a careful and thoughtful approach to Phase-1 clinical trials is ***(2-AEH2P)is a new cytostatic phospholipid agent that,unlike most chemotherapeutic drugs used today,does not target DNA or cytoskeleton,but act on the cell *** carried out by our group have shown several effects of 2-AEH2P controlling the progression of the cell cycle,in the alterations of the mitochondrial electrical potential capable of inducing apoptosis and autophagy in several types of human and animal tumor *** aim of this study is to establish the recommended safety dose of a 2-AEH2P monophosphoester,in dogs with tumor following the Phase 1 study model proposed by *** Phase-1 study following the Fibonacci model,2-AEH2P was safe at all staggered doses up to 150 mg/Kg for 8 *** administration in staggered doses according to the Fibonacci model,showed that the drug is safe,no advent of mortality during the study period or acute toxicity were *** is not a drug with hemolytic properties or that induces *** does not lead to changes in liver and renal functions and was able to modulate leukocyte production.2-AEH2P is new compound with antitumor potential,being useful for future veterinary and human tumors,as a combination of chemotherapeutic agents.

关键词： Cancer metabolism phospholipids monophosphoester Fibonacci Model clinical study.

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The Antiproliferative and Pro-apoptotic Role of 2-aminoethyl dihydrogen Phosphate in Triple-negative Breast Tumor Cells

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Journal of Pharmacy and Pharmacology 2021年第4期9卷 160-173页

作者： Antenor Pereira Bonfim Neto laertty garcia de sousa cabral Thalles Anthony Duarte Oliveira JulioCarlstron Pacheco Monique Gonçalves Alves Mercedes Reyes Hernández Rosa Andreia Nogueira Laiso Durvanei Augusto Maria University of São Judas Sao PauloSP 01246-000Brazil Faculty of Medicine University of Sao Paulo(FMUSP)Sao PauloSP 01246-000Brazil Laboratory of development and Innovation Butantan InstituteSao PauloSP 05503-900Brazil Faculty of Veterinary Medicine and Animal Science University of São Paulo(FMZUSP)São PauloSP 01246-000Brazil

Antineoplastic phospholipids are a new class of antitumor *** molecules interact with the plasma membrane,changing numerous pathways that induce cell death,with high selectivity for cancer cells.A representative of this class of antineoplastic agents is 2-aminoethyl dihydrogen phosphate(2-AEH2P).It is present in high intracellular concentrations in various tissues and organelles with antitumor,antiproliferative and pro-apoptotic ***,4T1 triple-negative tumor cells were treated in different concentrations in order to assess the cytotoxic potential and its effects on the modulation of cell death pathways in association with the chemotherapeutic drug Paclitaxel.2-AEH2P promoted cytotoxicity in tumor cells and significant morphological changes,however,it did not cause these effects in normal *** was positive regulation of proteins involved in the intrinsic pathway of cell death by apoptosis and regulation of the phases of cell cycle ***,structural and distribution changes in mitochondria,as well as decreased cell density and regression of the cytoskeleton were *** 2-AEH2P demonstrated a modulatory potential of apoptotic pathways inducing cell death,being a new compound with antitumor properties.

关键词： Breast cancer 2-aminoethyl dihydrogen phosphate apoptosis cell cycle

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Effect of Mucuna defatted Bran Extracted with Supercritical CO2 on Soybean Seed Germination

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Journal of Food Science and Engineering 2013年第4期3卷 187-195页

作者： Vitor Augusto dos Santos garcia Osvaldo Ferrarese-Filho Vladimir Ferreira cabral Ed Hoffmann Madureira Camila da Silva Lucio Cardozo-Filho department of Agronomy Universidade Estadual de Maringa Maringa PR 87020-900 Brazil department of Biochemistry Universidade Estadual de Maringa Maringa PR 87020-900 Brazil department of Chemical Engineering Universidade Estadual de Maringa Maringa PR 87020-900 Brazil department of Animal Reproduction Universidade de Sao Paulo Pirassununga SP 13635-900 Brazil department of Technology Universidade Estadual de Maringa Umuarama PR 87506-370 Brazil

In the present work, we investigated the effect of Mucuna deeringiana defatted bran on seed germination of soybean （Glycine max L. Merrill）. For this, the defatted bran was obtained from different operational conditions using CO2 under pressurized conditions as solvent. Oil extractions were carried out in a laboratorial scale unit at temperatures ranging from 310 to 330 K, pressure from 15 to 25 MPa and solvent flow set in 3 mL min^-1. The experiment was conducted in a germination chamber （25℃, 12：12 h light：dark photoperiod）, and the germination rate and germination speed index （GSI） were evaluated for seven days. The results showed that the oil extraction with supercritical CO2 concentrates the allelochemical L-3,4-dihydroxyphenylalanine （L-DOPA） in bran with levels from 1.86% to 4.65%. Subsequent experiments revealed that the rate of soybean seed germination was not affected by defatted bran whereas the GSI increased significantly after treatment. In brief, we concluded that the extraction process with supercritical CO2 is efficient to obtain L-DOPA of Mucuna, which influences the soybean seed germination.

关键词： L-DOPA Mucuna deeringiana soybean seed germination supercritical CO2 defatted bran

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Evaluation of Formaldehyde as a Potential Cause of Olfactory Dysfunction in Hairdressers

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Journal of Power and Energy Engineering 2023年第3期11卷 143-149页

作者： Linda Bitencourt cabral Mariana Andrade Miyamoto Natália Medeiros Dias Lopes Ellen Cristine Duarte garcia Tiago Severo Peixe Marco Aurélio Fornazieri department of Clinical Surgery Universidade Estadual de Londrina Londrina Brazil Medical School Pontifícia Universidade Católica do Paraná Londrina Brazil GEM Center of Excellence in Research Teaching and Health Care Londrina Brazil department of Clinical and Toxicological Analysis Universidade Estadual de Londrina Londrina Brazil

Objective: The aim of this study was to compare the olfactory function between hairdressers exposed to formaldehyde and unexposed controls, as exposure to toxic agents is a potential cause of olfactory disorders in humans. Hairdressing professionals frequently encounter formaldehyde, a component found in hair products that are known to have various toxic effects on the human body, including alterations in the sense of smell. Methods: A total of 32 hairdressing volunteers exposed to formaldehyde and 32 non-exposed volunteers matched for age, sex, education and smoking status underwent the University of Pennsylvania Smell Identification Test (UPSIT®). Results: The findings demonstrated a decrease in UPSIT® olfactory test scores and a higher degree of olfactory loss among hairdressers exposed to formaldehyde (mean UPSIT® scores: 30.6 vs 35.1, p Conclusion: Occupational exposure of hairdressers to formaldehyde is associated with diminished olfactory function. Education approach and promotion of personal protective equipment usage should be encouraged.

关键词： Formaldehyde Olfaction Disorders Occupational Medicine Toxicology

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Plasma-Induced γ-Fe Phase on S3A Alloy Ribbons

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材料科学与工程（中英文A版） 2011年第5X期1卷 632-638页

作者： A. cabral-Prieto N. Nava I. garcia-Sosa E. Camps Luis Escobar R. Lopez-Castafiarez O. Olea-Cardoso departamento de Quimica Instituto Nacional de Investigaciones Nucleares DeL Miguel Hidalgo 11801 Mexico D.F. Mexico Instituto Mexicano del Petroleo Eje Central Lazaro Cardenas 152 Col. San Bartolo Atepehuacan Del. Gustavo A. Madero C.P 07730 Mexico D.F. Mexico Facultad de Quimica Universidad Autonoma del Edo. de Mexico Toluca Edo. de Mexico Mexico

Amorphous alloy 2605S3A ribbons were exposed to cold plasmas of N2 and Ar-N2 at temperatures lower than Tx = 808 K. The X-ray diffraction patterns of the plasma treated ribbons, consist of a broad signal centered at 2θ = 45° characteristic of the amorphous state. The corresponding conversion X-ray M?ssbauer spectra of these ribbons consist of a superimposed singlet and a broadened magnetic sextet. The singlet with isomer shift δ = -0.11 mm/s can be assigned to γ-Fe austenite phase. Minor bulk magnetic changes in the alloy were measured as a consequence of these treatments, as analyzed from the resulting transmission M?ssbauer spectra. X-ray diffraction and M?ssbauer data of the crystallized samples are also reported. A qualitative assessment on the mechanical properties of the alloy associated with the presence of the γ-Fe phase is given. This γ-Fe phase can also be produced by simply heating the ribbons at temperatures as low as 423 K, an unexpected result.

关键词：等离子体温度非晶合金 Fe 诱导薄带等离子体处理穆斯堡尔同质异能移

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Diode Laser Cyclophotocoagulation in the Management of Pain and Intraocular Pressure Control in Patients with Terminal Glaucoma--Six Years’Experience

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Open Journal of Ophthalmology 2017年第2期7卷 88-94页

作者： Silvestre Cruz Diogo cabral Filipe Braz Ana Vide Escada Jorge Godinho Ferreira José Fernandes Joao Segurado Instituto de Oftalmologia Dr.Gama Pinto Centro de Responsabilidade de Oftalmologia do Hospital garcia de Orta LisbonPortugal

Objective: This study aims to describe the experience with diode laser cyclophotocoagulation in the control of intraocular pressure and resolution of pain in patients with refractory glaucoma. Methods: Retrospective study. 64 eyes of 60 patients who underwent cyclophotocoagulation between January 2008 and March 2014. Evaluation of the pre- and post-operative intraocular pressure, the control of ocular pain, the number of anti-glaucoma drugs used in pre- and post-intervention, the rate of complications and the success rate. Results: There was an overall success rate of 81.3%, with 9 eyes needing a second intervention. There was a mean reduction of 52.6% of the preoperative mean intraocular pressure of 41.25 to 19.56 mmHg at 12 months observation (p decreased number of anti-glaucoma drugs, sustained intraocular pressure reduction and resolution of pain.

关键词： Diode Laser Cyclophotocoagulation Glaucoma Painful Eye Intraocular Pressure Quality of Life

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