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G2/M inhibitors as pharmacotherapeutic opportunities for glioblastoma:the old,the new,and the future

Cancer Biology & Medicine 2018年第4期15卷 354-374页

作者： Angel Mauricio Castro-Gamero Julia Alejandra Pezuk mar.a sol brassesco Luiz Gonzaga Tone Human Genetics Laboratory Institute of Natural SciencesFederal University of Alfenas(UNIFAL-MG)Alfenas 37130-001Brazil Biotechnology and Innovation in Health Program and Pharmacy Program Anhanguera University Sao Paulo(UNIANSP)Sao Paulo 05145-200Brazil Department of Biology Faculty of PhilosophySciences and Letters at Ribeirao PretoUniversity of Sao PauloRibeirao Preto 14040-901Brazil Department of Pediatrics Department of Genetics Ribeirao Preto School of MedicineUniversity of Sao PauloRibeirao Preto 14049-900Brazil

Glioblastoma(GBM) is one of the deadliest tumors and has a median survival of 3 months if left untreated. Despite advances in rationally targeted pharmacological approaches, the clinical care of GBM remains palliative in intent. Since the majority of altered signaling cascades involved in cancer establishment and progression eventually affect cell cycle progression, an alternative approach for cancer therapy is to develop innovative compounds that block the activity of crucial molecules needed by tumor cells to complete cell division. In this context, we review promising ongoing and future strategies for GBM therapeutics aimed towards G2/M inhibition such as anti-microtubule agents and targeted therapy against G2/M regulators like cyclin-dependent kinases,Aurora inhibitors, PLK1, BUB, 1, and BUBR1, and survivin. Moreover, we also include investigational agents in the preclinical and early clinical settings. Although several drugs were shown to be gliotoxic, most of them have not yet entered therapeutic trials. The use of either single exposure or a combination with novel compounds may lead to treatment alternatives for GBM patients in the near future.

关键词： Chemotherapy PLK1 AURK survivin BUB BUR1

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How large are the extinct giant insular rodents? New body mass estimations from teeth and bones

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Integrative Zoology 2014年第2期9卷 197-212页

作者： Blanca MONCUNILL-solÉ Xavier JORDANA Nekane marÍN-MORATALLA Salvador MOYÀ-solÀ Meike KÖHLER Catalan Institute of Paleontology Miquel Crusafont Autonomous University of BarcelonaBellaterraSpain ICREA at Catalan Institute of Paleontology Miquel Crusafont Autonomous University of BarcelonaBellaterraSpain Department of Ecology University of BarcelonaSpain

The island rule entails a modification of the body size of insular mammals,a character related with numerous biological and ecological *** the Miocene to human colonization(Holocene),Mediterranean and Canary Islands were unaltered natural ecosystems,with paleofaunas formed with endemic giant rodents among other *** aim is to create methods to estimate the body masses of fossil island rodents and address the nature of ecological pressures driving the island *** created regression equations based on extant ro-dent data and used these to estimate the body masses of the extinct *** results show strong correlations between teeth,cranial and postcranial measurements and body mass,except for the length of the long bones,the transversal diameter of the distal tibia and the anteroposterior diameter of the proximal tibia,where the equa-tions were less *** use of equations obtained from a more homogeneous group(suborder and family)is preferable when analyzing the area of the first *** new regressions were applied to estimate the body masses of some Mediterranean and Canarian fossil rodents(Canariomys,*** 1.5 kg and *** 1 kg;Hypnomys,*** 230 g and *** 200 g;and Muscardinus cyclopeus 100 g).Our results indi-cate that under absence of predation,resource availability(island area)is the key factor that determines the size of the Canariomys ***,under presence of specialized predators(birds of prey),body size evolution is less pronounced(Hypnomys sp.).

关键词： body mass Canariomys Hypnomys island rule Muscardinus cyclopeus

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Functional properties of peptides obtained from whey proteins by ficin extract hydrolysis

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Food Bioscience 2022年第3期47卷 918-927页

作者： Afaf Kheroufi mar.a E.brassesco Débora A.Campos Halima Boughellout Manuela E.Pintado Laboratoire de Génie Agro-alimentaire équipe Génie des Procédés AlimentairesBiodiversité et Agro environnementInstitut de la Nutritionde l’Alimentation et des Technologies Agroalimentaires INATAAUniversité Frères Mentouri Constantine 1BP 325 Route de Ain El BeyConstantineAlgeria CBQF – Centro de Biotecnologia e Química Fina – Laboratório Associado Escola Superior de BiotecnologiaUniversidade Católica Portuguesa/PortoRua de Diogo Botelho 13274169-005PortoPortugal

Enzymatic whey proteins concentrates (WPC) hydrolysis under optimal conditions of ficin crude extract (FCE) in two ratios E/S (0.5 and 1%) was studied,assessing the impact of hydrolysis on WPC by determination degree of hydrolysis (DH),Fast proteins liquid chromatography (FPLC),Tricine SDS-PAGE,antioxidant activity at sampling time beside,and technological properties (solubility,emulsifying activity index (EAI) and foaming activity (FA)) at the best condition (maximum DH and antioxidant activity) other *** showed,in the first 30 min,DH reached 22.76% at E/S (1%) with a total degradation of α-lactalbumin (α-La) and almost of β-lactoglobulin (β-Lg).A significant increase in antioxidant activity and solubility was observed,while not for EAI,and *** results indicate for the first time that β-Lg is susceptible to hydrolyse by FCE that rarely found for other *** hydrolysates showed very relevant performance,and suggest that could be appropriate production of functional ingredients.

关键词： Whey proteins Ficin Hydrolysis Antioxidant solubility

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Base Excision Repair Inhibition by Methoxyamine Impairs Growth and Sensitizes Osteosarcoma Cells to Conventional Treatments

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Journal of Cancer Therapy 2014年第4期5卷 307-314页

作者： Ana Paula Montaldi Julia Alejandra Pezuk Elza Tiemi Sakamoto-Hojo Luiz Gonzaga Tone mar.a sol brassesco Department of Biology Faculty of Philosophy Sciences and Letters at Ribeirao Preto University of Sao Paulo Sao Paulo Brazil Department of Genetics Faculty of Medicine of Ribeirao Preto University of Sao Paulo Sao Paulo Brazil Department of Pediatrics Faculty of Medicine of Ribeirao Preto University of Sao Paulo Sao Paulo Brazil

The outcome of patients with osteosarcoma has not significantly improved in the last three decades. Therefore, there is still a need for the development of more effective therapeutic strategies. Methoxyamine (MX) is a base excision repair (BER) inhibitor that has shown anticancer potential by sensitizing a variety of tumor cells to ionizing radiation and chemotherapeutic drugs. In the present study, the in vitro antiproliferative effects of MX were evaluated in two osteosarcoma cell lines, HOS and MG-63. Evaluation of the influence on radiosensitivity and drug interactions in simultaneous treatments with methotrexate, doxorubicin, and cisplatin was also performed. Exposure to MX significantly decreased cell proliferation and mediated a substantial increase of apoptosis. Moreover, our results showed that MX synergized with ionizing radiation in both cell lines while potentiated the antitumor effects of cisplatin and methotrexate. Altogether, the results presented herein demonstrate the feasibility of inhibiting the BER pathway, which may in future be a promising strategy for overcoming intrinsic tumor resistance and to improve the outcome of patients with osteosarcoma.

关键词： Osteosarcoma Methoxyamine BER Cell Lines

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Alveolar rhabdomyosarcoma with breast involvement

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Chinese Medical Journal 2013年第5期126卷 998-998页

作者： Elvis Terci Valera mar.a sol brassesco Valdair Francisco Muglia Carlos Alberto Scrideli Luiz Gonzaga Tone Division of Pediatric Oncology Department of PediatricsFaculty of Medicine of Ribeir(a)o Preto University of S(a)o Paulo Brazil Division of Radiology Internal Medicine Department Faculty of Medicine of Ribeir(a)o Preto University of S(a)o Paulo Brazil

To the editor： We have read with interest the recently published article by Li et al focusing on the clinicopathologic features and biological behavior of five female patients presenting with rhabdomyosarcoma （RMS） of the breast. Actually, the occurrence of RMS in this location, either primarily or as a metastatic disease, is a very rare event and the impact of this clinical presentation on treatment and outcome remains poorly defined. Moreover, the diagnosis of breast involvement by RMS may be challenging, particularly due to the rarity of this clinical presentation.

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Diagnostic value of sperm DNA fragmentation and sperm high-magnification for predicting outcome of assisted reproduction treatment

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Asian Journal of Andrology 2013年第6期15卷 790-794,I0008-I0009页

作者： Gemma López Rafael Lafuente Miguel A Checa Ramón Carreras mario brassesco Centre de Infertilidad y Reproduccion Humana (ClRH) E-08017 Barcelona Spain Department of Obstetrics and Gynecology Hospital Universitari del Mar Universitat AutOnoma de Barcelona E-08003 Barcelona Spain

Over the last years, major improvements in the field of male infertility diagnosis have been achieved. The aim of this study was to determine the diagnostic usefulness of sperm DNA integrity and sperm vacuolisation for predicting outcome in infertile couples undergoing in vitroferti lisation （IVF） and intracytoplasmic sperm injection （ICSI） treatments. A cohort study from 152 infertile couples undergoing sperm DNA fragmentation and high-magnification tests prior to an assisted reproduction treatment was designed. We found that the most predictive cutoff for pregnancy was 25.5% of DNA fragmentation with a negative predictive value of 72.7% （P=0.02）. For the degree of vacuolisation, the best predictor of pregnancy was 73.5% of vacuolated sperm grades Ⅲ ＋ Ⅳ with a negative predictive value of 39.4% （P=0.09）, which was not statistically significant. In conclusion, sperm DNA fragmentation greater than 25.5% could be associated with higher probability of failure IVF treatment. Regarding the results of the sperm analysis at high magnification, they do not allow us to predict whether or not oatients will become pregnant.

关键词： DNA fragmentation high-magnification IVF vacuoles

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Diabetes mellitus, revascularization and outcomes in elderly patients with myocardial infarction-related cardiogenic shock

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Journal of Geriatric Cardiology 2020年第10期17卷 604-611页

作者： Miquel Gual Albert Ariza-solé mar.a García Márquez Cristina Fernández JoséL Bernal Francesc Formiga mar.a-Isabel Barrionuevo JoséC Sánchez-Salado Victòria Lorente Júlia Pascual Isaac Llaó Oriol Alegre Angel Cequier Javier Elola Hospital Universitari de Bellvitge L’Hospitalet de LlobregatBarcelonaSpain Fundación Instituto para la Mejora de la Asistencia Sanitaria MadridSpain Hospital Clínico Universitario San Carlos MadridSpain Hospital Universitario 12 de Octubre MadridSpain

Background The prognostic role of diabetes mellitus(DM)in elderly patients with myocardial infarction-related cardiogenic shock(MI-CS)remains *** information exists about the impact of intensive cardiac care unit(ICCU)and revascularization on outcomes of elderly patients with *** aimed to assess the prognostic impact of DM according to age in patients with MI-CS,and to analyze the impact ICCU management and revascularization on in-hospital mortality in MI-CS patients at older *** Discharge episodes with diagnosis of CS associated with MI were selected from the Spanish National Health System’s Basic Data *** were classified according to their availability of *** outcome measured was in-hospital *** A total of 23,590 episodes of MI-CS were identified,of whom 12,447(52.8%)were in patients aged≥75 *** impact of DM on in-hospital mortality was different among age *** in younger patients,DM was associated to a higher mortality risk(0.52 vs.0.47,OR=1.12,95%CI:1.06–1.18,χ^2<0.001),this association became non-significant in older patients(0.76 vs.0.81,χ^2=0.09).Adjusted mortality rate of MI-CS aged≥75 years was lower in patients admitted to hospitals with ICCU(adjusted mortality rate:74.2%vs.77.7%,P<0.001)and in patients undergoing revascularization(74.9%vs.77.3%,P<0.001).Conclusions Prognostic impact of DM in patients with MI-CS was different according to age,with a significantly lower impact at older *** availability of ICCU and revascularization were associated with better outcomes in these complex patients.

关键词： Cardiogenic shock Diabetes mellitus Myocardial infarction Revascularization The elderly

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A Novel Method to Improve Quality of Drinking Water, Based on the Eye’s Biology

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Journal of Water Resource and Protection 2022年第4期14卷 318-333页

作者： Arturo solís Herrera mar.a del Carmen Arias Esparza martha Patricia solís Arias Human Photosynthesis^TM Research Centre Aguascalientes México

Water represents a critical nutrient, the absence of which will be lethal within days. Water’s importance for the prevention of nutrition-related noncommunicable diseases has received more attention recently. There are major gaps in knowledge related to the measurement of total fluid intake and hydration status at the population level. It is poorly understood the effects of chronic mild dehydration and fluid consumption on specific health outcomes including obesity. Urolithiasis is the only disorder that has been consistently associated with chronic low daily water intake. Water is an essential nutrient required for life, but until now, it was considered mainly as a universal solvent, which served to prepare the broth of life inside the cells, but the function of water now takes unusual importance with our discovery of the unsuspected ability of the human body to transform the power of light into chemical energy by dissociating the molecule from water, as it happens in plants. The process that we replicated in the laboratory for the first time in 2007, represents a light at the end of the tunnel, in the growing and serious problem of contamination of the mysterious and vital liquid that we call water.

关键词： Drinking Water Hydrogen Oxygen Dissolved Oxygen Pollution Human Eye

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Evaluation of the Effectiveness of Workplace Health Promotion Programs from 2000 to 2020: Literature Review

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Open Journal of Preventive Medicine 2021年第4期11卷 113-131页

作者： Siguero mar.a-Ángeles Jerónimo Maqueda marqués Francisco Sagües mar.a-Jesús solé mar.a-Dolores Health Promotion and Occupational Epidemiology Department National Institute for Safety and Health at Work Madrid Spain National Centre for Working Conditions National Institute for Safety and Health at Work Barcelona Spain

Introduction. Recognition of best practices in workplace health promotion is an important task that significantly affects the expansion of those programs. Once the program has been developed, its effectiveness becomes the most critical point of evaluation to guarantee achievements in the improvement of workers’ health. Objectives. To identify the practices for evaluating the effectiveness of workplace health promotion programs. Material and Methods: A search was performed on MEDLINE through PubMed with the MeSH: “Occupational Health”, “Health Promotion” and “Program Evaluation”, from the year 2000 to the year 2020 for studies with the following designs: Meta-analyses, Systematic reviews, Randomized Clinical Trials and Clinical Trials. Results: The most common topic of workplace health promotion programs (WHP) was increasing physical activity and avoiding a sedentary lifestyle, followed by stress management and finally smoking cessation and musculoskeletal disorders. The post-intervention measurements were most often done at 6 months and 12. The most commonly used indicators were the number of steps, weight, BMI, % body fat, waist circumference, blood pressure, sedentary time, level of physical activity and time of moderate-vigorous physical activity, daily energy output, life purpose, life satisfaction, mood and stress level. Conclusions: Although a great variability was observed in the evaluation of WHP programs, there were also common aspects. These results will help with designing WHP programs and defining evidence-based evaluation of their effectiveness. It is important to remember that WHP programs must be customized, taking into consideration the needs of each organization’s workforce.

关键词： Occupational Health Health Promotion Effectiveness Evaluation

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Experimental model standardizing polyvinyl alcohol hydrogel to simulate endoscopic ultrasound and endoscopic ultrasoundelastography

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World Journal of Gastroenterology 2020年第34期26卷 5169-5180页

作者： Elymir S Galvis-García Sergio Sobrino-Cossío Arturo Reding-Bernal Yesica Contreras-marín Karina solórzano-Acevedo Patricia González-Zavala Rosa M Quispe-Siccha Unidad de Endoscopía Gastrointestinal Hospital General de México"Dr.Eduardo Liceaga"Mexico 06720Mexico Unidad de Endoscopia y Fisiología Digestiva HospitalÁngeles del PedregalMexico 10700Mexico Dirección de Investigación Hospital General de México“Dr.Eduardo Liceaga”Mexico 06720Mexico Unidad Profesional Interdisciplinaria de Biotecnología and Unidad de Investigación y Desarrollo Tecnológico Instituto Politécnico Nacional and Hospital General de México"Dr.Eduardo Liceaga"Mexico 06720Mexico Instituto de Investigaciones en Materiales and Unidad de Investigación y Desarrollo Tecnológico Universidad Nacional Autónoma de México and Hospital General de México"Dr.Eduardo Liceaga"Mexico 06720Mexico Unidad de Investigación y Desarrollo Tecnológico Hospital General de México"Dr.Eduardo Liceaga"Mexico 06720Mexico

BACKGROUND Endoscopic ultrasound(EUS)and endoscopic ultrasound elastography(EUS-E)simulation lessens the learning curve;however,models lack realism,diminishing *** To standardize the mechanical properties of polyvinyl alcohol(PVA)hydrogel for simulating organs and digestive *** PVA hydrogel(Sigma Aldrich,degree of hydrolysis 99%)for simulating EUS/EUS-E lesions was investigated in Unidad de Investigación y Desarrollo Tecnológico at Hospital General de México“*** Liceaga”,Mexico *** evaluated physical,contrast,elasticity and deformation coefficient characteristics in lesions,applying Kappa’s concordance and satisfaction questionnaire(Likert 4-points).RESULTS PVA hydrogel showed stable mechanical *** depended on molecular weight(MW)and concentration(C).PVA bblocks with the greatest density showed lowest tensile strength(r=-0.8,P=0.01).Lesions were EUSgraphically *** and heterogeneous examples were created from PVA blocks or PVA phantoms,exceeding(MW2=146000-186000,C9=15%and C10=20%)with a density under(MW1=85000-124000,C1=7%and C2=9%).We calculated elasticity and deformation parameters of solid(blue)areas,contrasting with the norm(Kappa=0.8;high degree of satisfaction).CONCLUSION PVA hydrogels were appropriate for simulating organs and digestive lesions using EUS/EUS-E,facilitating practice and reducing *** amplified skills,while reducing the learning curve.

关键词： Endoscopic ultrasound simulators in endoscopy Polyvinyl alcohol Endoscopic ultrasound Endoscopic ultrasound elastography Strain Elasticity

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