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Personalized medicine in gastric cancer:Where are we andwhere are we going?

World Journal of Gastroenterology 2016年第3期22卷 1160-1171页

作者： Alexandre A Jácome Anelisa K Coutinho Enaldo M lima Aline C andrade JoséSebastião dos Santos Department of Medical Oncology Hospital Mater DeiBelo Horizonte 30190-131Minas GeraisBrazil Department of Gastrointestinal Oncology Brazilian Gastrointestinal Tumor GroupClinica AMOSalvador 41950-640BahiaBrazil Department of Surgery and Anatomy University of São Paulo at Ribeirão PretoSchool of MedicineRibeirão Preto14049-900São PauloBrazil

Despite improvements in adjuvant therapies for gastric cancer in recent years, the disease is characterized by high recurrence rates and a dismal prognosis. The major improvement in the treatment of recurrent or metastatic gastric cancer in recent years has been the incorporation of trastuzumab, a monoclonal antibody that inhibits human epidermal growth factor receptor 2(HER2) heterodimerization, after the demonstrated predictive value of the overexpression and/or amplification of this receptor. Beyond HER2, other genetic abnormalities have been identified, and these mutations may be targetable by tyrosine kinase inhibitors or monoclonal antibodies. The demonstration of four distinct molecular subtypes of gastric cancer by the Cancer Genome Atlas study highlight the enormous heterogeneity of the disease and its complex interplay between genetic and epigenetic alterations and provide a roadmap to implement genome-guided personalized therapy in gastric cancer. In the present review, we aim to discuss, from a clinical point of view, the genomic landscape of gastric cancer described in recent studies, the therapeutic insights derived from these findings, and the clinical trials that have been conducted and those in progress that take into account tailored therapies for gastric cancer.

关键词： stomach neoplasms biological markers Molecular targeted therapy Individualized medicine Transcriptome

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Antihyperglycemic effect of Passiflora glandulosa cav. fruit rinds flour in streptozotocin-induced diabetic mice

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Asian Pacific Journal of Tropical Medicine 2018年第9期11卷 510-517页

作者： Erlandia Alves Magalhaes Queiroz Raquel Teixeira Terceiro Paim Sandra Machado Lira Jose Ytalo Gomes da Silva carla Laine Silva lima Marcelo Oliveira Holanda Stephen Rathinaraj Benjamin Icaro Gusmao Pinto Vieira Maria Izabel Florindo Guedes Biotechnology and Molecular Biology Laboratory State University of CearaFortaleza Ceara Brazil Technological Development Park(PADETEC) Federal University of CearaPici Campus Fortaleza Ceara Brazil

Objective:To investigate the effect of administration of Passiflora glandulosa(***) fruit rinds flour on streptozotocin(STZ)-induced diabetic ***:The preliminary phytochemical screening and parameters such as centesimal composition and brine shrimp toxicity were *** in vivo study Swiss female mice were divided into four groups:NC-normal control;DC-diabetic control animals receiving saline;MET-diabetic animals receiving metformin(200 mg/kg);PFRF-diabetic animals receiving *** fruit rinds flour(200 mg/kg).All of them were treated for 28 *** was used in a single dose of 120 mg/kg to establish diabetic *** weight,water and food intake,fasting blood glucose were *** analysis of pancreas and liver were performed to evaluate STZ-induced tissue ***:Phytochemical screening showed the presence of flavanones and *** *** fruit rinds flour was non-toxic by the brine shrimp *** fruit rinds flour also reduced the loss of body weight and significantly decreased food intake in the diabetic ***,a significant reduction in blood glucose was observed for 15 d and this was maintained on 21 d and 28 d when compared with diabetic ***,the *** fruit rinds flour has a favourable effect on the histopathological changes of the pancreas in STZ induced ***:It is concluded that *** fruit rinds flour is a natural product that contains potent antioxidant compounds and presents good prospects for the improvement of diabetic mellitus by reducing serum glucose levels.

关键词： Diabetes mellitus Passiflora Blood glucose Histology Streptozotocin Mice

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A New Biomaterial for Urinary Catheters

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Journal of Biomaterials and Nanobiotechnology 2018年第1期9卷 1-12页

作者： Roberto Santos lima Salvador Vilar Correia lima José Lamartine De andrade Aguiar Eziel Cavalcanti Vasconcelos Rocha Flávia Cristina Morone Pinto Life Sciences Center Federal University of Pernambuco (UFPE) Caruaru Brazil Postgraduate Program in Surgery Department of Surgery Center for Health Sciences Federal University of Pernambuco (UFPE) Recife Brazil

Several studies argue that an ideal biomaterial for urinary catheters is utopian. Based in literature review it seems to be true. However, research advances: the biomaterial itself, new designs, new coatings, associated drugs, etc. Once implanted and interacting with urine, two old problems persist: encrustation and bacterial colonization. In this context, an extracellular product from bacterial synthesis on sugarcane molasses biomaterial has been studied in several experimental and clinical studies. Based on its high biocompatibility, the aim of this study is to evaluate its performance in an in vivo model as an endourologic prosthesis implanted in the bladder of Wistar rats. We evaluate physical, chemical and biological phenomena in comparison to an already established biomaterial, polyurethane. Even though it is not a finished product, the sugarcane biopolymer presented similar performance compared to polyurethane in several analyzed parameters and has an important characteristic: low cost.

关键词： Biomaterial Urinary Catheters Encrustation

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Quantification of the Expression of HIF-1alpha by Real-Time PCR in Rat Hepatocytes Cultures Invaded by <i>Shigella flexneri</i>under Normoxic and Hypoxic Conditions

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Advances in Microbiology 2015年第7期5卷 507-516页

作者： Camila Bárbara Cantalupo lima Sania Alves dos Santos Dahir Ramos de andrade Júnior Laboratory of Bacteriology (LIM 54) Department of Infectious and Parasitic Diseases Faculty of Medicine University of Sao Paulo Sao Paulo Brazil

Aim: Shigella flexneri (S. flexneri) is a gram-negative enterobacterium responsible for severe intestinal end systemic infection in humans. The bacteria can reach the liver due to degeneration of the colonic epithelium. Hypoxia is present in many human diseases and can induce the expression of the transcription factor HIF-1alpha that may have a cell protective role. The influence of hypoxia and HIF-1alpha on bacterial infection, studied in this work, is unclear. Hypoxia inducible factor-1alpha (HIF-1alpha) is a transcription factor that acts as a master regulator of gene expression induced by hypoxia. Methods: We compared the ability of S. flexneri to invade rat hepatocytes in primary culture both in normoxic and hypoxic conditions. We evaluated TNF-alpha released by hepatocytes, apoptosis rate and HIF-1alpha expression by confocal microscopy as well as real time PCR technique. Results: We showed that S. flexneri invaded less hepatocytes previously submitted to 24 h hypoxia (6.5% O2) than those cultivated in normoxia (21% O2). S. flexneri also induced HIF-1α expression in hepatocytes, TNF-α secretion and apoptosis. Conclusion: a) Hypoxia alone was not a stimulus to TNF-α secretion, but induced cell apoptosis and HIF-1α expression;b) S. flexneri was able to invade rat hepatocytes and hypoxia apparently influenced significantly bacterial cell invasiveness;c) HIF-1α was expressed in hypoxic conditions, and it was also stimulated by S. flexneri.

关键词： Shigella flexneri Hepatocytes Cell Hypoxia Hypoxia-Inducible Factor 1α TNF-Alpha Apoptosis

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Clinical Application of Dynamic Gait Index-Brazilian Brief Version

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Advances in Aging Research 2018年第6期7卷 113-118页

作者： Carlos Kazuo Taguchi élida Pinto Costa Lucas Vieira Alves Larissa Karoline Santos Erbson Rodrigues de Oliveira Silva Brenda carla de lima Araújo Fabíola Andréa andrade dos Santos Allan Robert da Silva Audiology Departament Federal University of Sergipe S&atilde o Cristóvã o Brazil Federal University of Sergipe S&atilde o Cristóvã o Brazil Education Coordinator of Sergipe State Aracaju Brazil Speech Therapist and Audiology Departament Federal University of Sergipe S&atilde o Cristóvã o Brazil University Hospital Board Federal University of Sergipe S&atilde o Cristóvã o Brazil Statistical Departament Federal University of Sergipe S&atilde o Cristóvã o Brazil

Introduction: In elderly, the progressive degenerations in the nervous system and vestibular system compromise the human body balance leading to a greater risk of falls. The Dynamic Gait Index is a protocol that predicts risks to falls in seniors. Objective: To analyze the results of the application of the Dynamic Gait Index (DGI)-Brazilian brief proposal and establish correlation with the original version. Methods: Study approved by the Ethics and Research Committee of Federal University of Sergipe (number 0197.0.107000.09). We analyzed 223 files of socially active elderly, female gender, aged ranged 60 to 85 years, mean 68.54 (±7.61) years since 2014. The volunteers were evaluated by the DGI-Brazil. For the statistical analysis, the Pearson Correlation Momentum Correlation Test with Spearman Correlation was used, with p ≤ 0.05 and r = 1.0. Results: Sixty-three (27.8%) of the volunteers presented an altered DGI scores. The statistical analysis indicated that Task 1 and Task 2 did not contribute to decrease the total score in the test. The worst performances occurred in Tasks 3, 5 and 6. There was founded a positive correlation between Tasks 1 and 2;1 and 8;3 and 4;3 and 5;4 and 5;2 and 4;2 and 7. Negative correlation occurred between Tasks 4 and 8, and 6 was not correlated with another Task. Conclusion: The DGI-Brazilian brief version presented an excellent correlation with the original proposal and may be useful in clinical practice as a tool to evidence future risks of falls in the elderly people.

关键词： Aged Postural Balance Accidental Falls Clinical Protocols

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Probe-based confocal endomicroscopy is accurate for differentiating gastric lesions in patients in a Western center

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Chinese Journal of Cancer Research 2018年第5期30卷 546-552页

作者： adriana vaz safatle-ribeiro elisa ryoka baba rodrigo corsato scomparin sheila friedrich faraj marcelo simas de lima luciano lenz bruno costa martins carla gusmon fábio shiguehissa kawaguti caterina pennacchi bruno zilberstein ulysses ribeiro jr. fauze maluf-filho Endoscopy Unit of Department of Gastroenterology Sao Paulo Cancer Institute University of Sao Paulo Medical School (ICESP-HCFMUSP) Sao Paulo 01246-000 Brazil

Objective： Probe-based confoeal laser endomicroscopy （pCLE） technique may improve the diagnosis of gastric mucosal lesions allowing acquisition of high-resolution in vivo images at the cellular and mierovaseular levels. This study aims to evaluate the accuracy of pCLE for the differential diagnosis of non-neoplastic and neoplastic gastric ***： Twenty gastric mucosal lesions from 10 patients were evaluated during endoscopic procedure and were examined by pCLE. Diagnostic pCLE was followed by biopsies or endoscopic resection of suspected lesions. A senior pathologist evaluated the specimens and was blinded to the pCLE ***： Patients＇ mean age was 68.3 （range, 42-83） years and six were men. Thirteen suspicious flat or elevated lesions （classified as 0-Is, 0-IIa or 0-IIa ＋ IIc） and seven pre-malignant lesions （atrophy and intestinal metaplasia） were evaluated. One patient was studied during his long-term follow-up after partial gastrectomy and presented severe atrophy, intestinal metaplasia, and xanthomas at the stump mucosa. The location of gastric lesions was in the body （n=10 lesions）, the antrum （n=9） and the incisura angularis （n=1）. All neoplastic lesions and all but one benign lesion were properly diagnosed by pCLE. pCLE incorrectly diagnosed one small antrum lesion as adenoma, however the final diagnosis was intestinal metaplasia. The final histological diagnosis was neoplastic in 9 and benign lesions in 11. In this small case series, pCLE accuracy was 95% （19/20 lesions）.Conclusions： pCLE is accurate for real time histology of gastric lesions, pCLE may change the management of patients with gastric mucosal lesions, guiding biopsies and endoscopic resection, and avoiding further diagnostic workup or unnecessary therapy.

关键词： Probe-based confocal endomieroscopy gastric cancer intestinal metaplasia atrophy gastric adenoma endoscopic resection

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Delirium in hospitalized patients: Cohort observational in infirmary of medical clinic

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Open Journal of Preventive Medicine 2012年第2期2卷 190-195页

作者： Rilva Lopes de Sousa-Munoz Leila Coutinho Taguchi Mara Rufino de andrade Katyara Mylena Silveira Ribeiro lima Federal University of Paraiba(UFPB) Joao PessoaBrazil Lauro Wanderley University Hospital(LWUH) Joao PessoaBrazil

Objectives: To determine prevalence, incidence and risk factors of delirium in hospitalized patients in the infirmary of medical clinic of the Lauro Wanderley University Hospital. Method: An observational cohort study evaluating 140 patients over 18 years between admission and discharge. The survey instrument was the Confusion Assessment Method. Results: The prevalence of delirium was 5.7% (8/140) and the incidence, 2.1%. In patients with delirium were observed alteration of sleep-wake cycle (6/75%), altered level of consciousness (6/75%), disorganized thinking (5/62, 5%) and psychomotor retardation (5/62 5%). There was a significant association of delirium and age, mechanical restraint in bed, prior history of cognitive impairment, auditory and visual sensory deficit, psychiatric hospitalization, poor health status and mortality. Conclusions: The prevalence of delirium at admission was lower than that found in other studies, but it was a predictor factor of hospital mortality.

关键词： Delirium Hospitalization Risk Factors Mortality

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Sex-specific effects of Eugenia punicifolia extract on gastric ulcer healing in rats

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World Journal of Gastroenterology 2018年第38期24卷 4369-4383页

作者： Larissa Lucena Périco Vinícius Peixoto Rodrigues Rie Ohara Gabriela Bueno Vania Vasti Alfieri Nunes Raquel Cássia dos Santos Ana Carolina lima Camargo Luis Antuio Justulin Joior Sérgio Faloni de andrade Viviane Miranda Bispo Steimbach Luísa Mota da Silva Lúcia Regina Machado da Rocha Wagner Vilegas Catarina dos Santos Clélia Akiko Hiruma-lima Department of Physiology Institute of BiosciencesSa Paulo State University(UNESP)Botucatu 18618-970Sa PauloBrazil Laboratory of Bioactive Compounds Sao Francisco UniversityBraganca Paulista 12916-900Sa PauloBrazil Department of Morphology Institute of BiosciencesSao Paulo State University(UNESP)Botucatu 18618-970Sao PauloBrazil Programa de Po-graduacao em Ciecias Farmaco-ticas Nuleo de Investigacoes Quiico-Farmaceticas(NIQFAR)Universidade do Vale do Itajai-UNIVALIItajai 88302-901Santa CatarinaBrazil Coastal Campus of Sa Vicente Sa Paulo State University(UNESP)Sa Vicente 11330-900Sa PauloBrazil Department of Biological Science Faculty of Sciences and LanguagesSa Paulo State University(UNESP)Assis 19806-900SaPauloBrazil

AIM To evaluate the sex-specific effects of a hydroalcoholic extract from Eugenia punicifolia(HEEP) leaves on gastric ulcer *** In this rat study involving males, intact(cycling) females, and ovariectomized females, gastric ulcers were induced using acetic acid. A vehicle, lansoprazole, or HEEP was administered for 14 d after ulcer induction. Body weight was monitored throughout the treatment period. At the end of treatment, the rats were euthanized and the following in vivo and in vitro investigations were performed: macroscopic examination of the lesion area and organ weights, biochemical analysis, zymography, and evaluation of protein expression levels. Additionally, the concentration-dependent effect of HEEP was evaluated in terms of subacute toxicity and *** Compared to the vehicle, HEEP demonstrated a great healing capacity by substantially reducing the ulcerative lesion area in males(52.44%), intact females(85.22%), and ovariectomized females(65.47%), confirming that HEEP accelerates the healing of acetic acidinduced gastric lesions and suggesting that this effect is modulated by female sex hormones. The antiulcer effect of HEEP was mediated by prostaglandin E2 only in male rats. Overall, the beneficial effect of HEEP was the highest in intact females. Notably, HEEP promoted the expression of vascular endothelial growth factor(intact vs ovariectomized females) and decreased the expression of Caspase-8 and Bcl-2(intact female vs male or ovariectomized female). Additionally, HEEP enhanced fibroblast proliferation and migration into a wounded area in vitro, confirming its healing effect. Finally, no sign of subacute toxicity or cytotoxicity of HEEP was *** In gastric ulcers, HEEP-induced healing(modulated by female sex hormones; in males, mediated by prostaglandin) involves extracellular matrix remodeling, with gastric mucosa cell proliferation and migration.

关键词： Eugenia punicifolia Gastric ulcer healing Acetic acid Sex difference Myrtaceae Toxicity

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Brazilian biosafety law and the new breeding technologies

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Frontiers of Agricultural Science and Engineering 2020年第2期7卷 204-210页

作者： Alexandre lima NEPOMUCENO Renata FUGANTI-PAGLIARINI Maria Sueli Soares FELIPE Hugo Bruno Correa MOLINARI Edivaldo Domingues VELINI Eduardo Romano de Campos PINTO Maria Lucia Zaidan DAGLI Galdino andrade FILHO Patricia Machado Bueno FERNANDES Embrapa Soybean Londrina 86001970Brazil Catholic University of Brasilia Brasilia 70790160Brazil Embrapa Agroenergy Biological Station ParkBrasilia 70770901Brazil Paulista State University Julio de Mesquita Filho Botucatu Faculty of Agronomic SciencesBotucatu 18610307Brazil Embrapa Biotechnology and Genetic Resources—Biological Station Park Brasilia 70770900Brazil Sao Paulo University Veterinary FacultySao Paulo 05508900Brazil Londrina State University Microbiology DepartmentUniversity CampusLondrina 86051990Brazil Espirito Santo Federal University Biotechnology Post GraduationVitoria 29040090Brazil CTNBio(National Biosafety Technical Commission) Brasilia 70610200Brazil

Globally,the area of land cultivated with genetically modified(GM)crops has increased a thousand-fold over the last two *** this technology has become important for food production,the regulatory frameworks that underpin these outcomes are based on a list of requirements for a risk assessment that differ from country to *** recent years,policymakers have had the opportunity to learn from the controversies over transgenics to create effective regulatory milestones for emerging technologies,allowing them to reach their potential for a more sustainable agriculture,ensuring food *** Brazil,Law No.11.105 of 24 March 2005 established a framework with four main organizations responsible for risk assessment and ***,most of new breeding technologies did not exist at that time and were not considered in this ***2016,Normative Resolution No.16 of the National Biosafety Technical Commission(CTNBio)was established to address this gap based on the evaluation of the products obtained through these techniques(termed Innovative Precision Improvement Techniques in the resolution),in a case-by-case consultation ***,if the product is designated to be a GM,the developer will have to go through the biosafety requirements and will be approved only after CTNBio risk *** the product is designated not to be GM(for the purposes of the legislation),then it can be registered using the existing ***,152 GM products are commercially approved in *** 2018,CTNBio assessed the first consultation on commercial release of plants generated using the new breeding technologies and has subsequently approved six *** is expected that many institutions would be able to participate in Brazilian and world markets,developing and introducing new biotechnological solutions and products through a more sustainable approach and without facing public disapproval,a common issue for GM crops.

关键词： Brazilian legislation CTNBio genetically modified crops

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Rock Cutting Analysis Employing Finite and Discrete Element Methods

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Journal of Mechanics Engineering and Automation 2016年第2期6卷 100-108页

作者： carla Massignani Carrapatoso Carlos Emmanuel Ribeiro Lautenschlager Guilherme lima Righetto Sergio Augusto Barreto da Fontoura and Nelson Inoue Civil Engineering Department Pontifical Catholic University of Rio de Janeiro Rio de Janeiro 22451-900 Brazil

The petroleum industry has shown great interest in the study of drilling optimization on pre-salt formations given the low rates of penetration observed so far. Rate of penetration is the key to economically drill the pre-salt carbonate rock. This work presents the results of numerical modeling through finite element method and discrete element method for single cutter drilling in carbonate samples. The work is relevant to understand the mechanics of drill bit-rock interaction while drilling deep wells and the results were validated with experimental data raised under simulated downhole conditions. The numerical models were carried out under different geometrical configurations, varying the cutter chamfer size and back-rake angles. The forces generated on the cutter are translated into mechanical specific energy as this parameter is often used to measure drilling efficiency. Results indicate that the chamfer size does not change significantly the mechanical specific energy values, characteristic. Results also show there is a significant increase although the cutter aggressiveness is influenced by this geometrical in drilling resistance for larger values of back-rake angle.

关键词： Rock cutting discrete element method finite element method single cutter test.

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