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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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HER2 in gastric cancer: Comparative analysis of three different antibodies using whole-tissue sections and tissue microarrays

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World Journal of Gastroenterology 2013年第38期19卷 6438-6446页

作者： Lucas Faria Abraho-Machado Alexandre Andrade dos Anjos Jácome Durval Renato Wohnrath josé sebastio dos santos Estela Cristina Carneseca josé Humberto Tavares Guerreiro Fregnani Cristovam Scapulatempo-Neto Department of Pathology Barretos Cancer HospitalBarretosSao Paulo 14784-400Brazil Department of Clinical oncology Mater Dei HospitalBelo HorizonteMinas Gerais 30140-092Brazil Department of Gastrointestinal Surgical oncology Barretos Cancer HospitalBarretosSao Paulo 14784-400Brazil Department of Surgery and Anatomy University of S o Paulo-Ribeir o Preto School of MedicineRibeir o PretoSao Paulo 14049-900Brazil Biostatistician at Cancer Registry Department Barretos Cancer HospitalBarretosSao Paulo 14784-400Brazil Researcher Support Center Barretos Cancer HospitalBarretosSao Paulo 14784-400Brazil

AIM:To compare the performance of three commercially available anti-human epidermalgrowth factor receptor 2(HER2)antibodies in whole-tissue sections and tissue microarrays(TMAs)of a series of gastric ***:We present a comparative analysis of three anti-HER2 antibodies(HercepTest,4B5 and SP3)using TMA and whole-tissue sections prepared from the same paraffin blocks of 199 gastric adenocarcinomas operated upon between January 2004 and December2008 at a Brazilian cancer *** data on the patients’age,sex,the anatomical location of the tumor and the Lauren’s histological classification were collected from clinical and pathological *** immunohistochemical(IHC)results were examined by two pathologists and the cases were classified as positive(3+),equivocal(2+)and negative(0 or 1+),according to the criteria of the IHC scoring system of gastric *** and whole-tissue sections were evaluated separately and *** cases yielding discordant IHC results and/or scored as 2+were subjected to dual-color in situ hybridization in order to determine the final HER2 *** determining the sensitivity and predictive value for HER2-positive status,we measured the accuracy of each antibody by calculating the area under the receiver operating characteristic(RoC)*** agreement between the results obtained using the TMAs and those obtained using the whole-tissue sections was assessed by means of Kappa ***:Intratumoral heterogeneity of HER2 expression was observed with all ***2-positive expression(3+)in the whole-tissue sections was observed in 23 cases(11.6%)using the 4B5 antibody,in 18 cases(9.1%)using the SP3 antibody and in 10 cases(5.1%)using the HercepTest *** the TMAs,11 positive cases(5.6%)were identified using SP3 antibody,9(4.6%)using the 4B5 antibody and 6(3%)using the HercepTest *** sensitivity using whole-tissue sections and TMA,respectively,was 95.2%and 42.9%with 4B5,90.5%and 66.7%

关键词： Gastric cancer Human epidermalgrowth factor receptor 2 Immunohistochemistry Whole-tissue sections Tissue microarray Trastuzumab

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Study of the patency of different peritoneal drains used prophylactically in bariatric surgery

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World Journal of Gastroenterology 2009年第19期15卷 2340-2344页

作者： Wilson Salgado Júnior Marcelo Martins Macedo Neto josé sebastio dos santos Ajith Kumar Sakarankutty Reginaldo Ceneviva orlando de Castro e Silva Jr Department of Surgery and Anatomy Medical School of Ribeiro Preto of the University of So PauloR.Antnio Chiericato760Ribeiro Preto-SP 14096-510Brazil

AIM:To compare the performance of different types of abdominal drains used in bariatric ***:A vertical banded Roux-en-Y gastric bypass was performed in 33 morbidly obese *** of the peritoneal cavity was performed in each case using three different types of drain selected in a randomized manner:a latex tubular drain,a Watterman tubulolaminar drain,and a silicone channeled *** permeability,contamination of the drained fluid,ease of handling,and patient discomfort were evaluated postoperatively over a period of 7 ***:The patients with the silicone channeled drain had larger volumes of drainage compared to patients with tubular and tubulolaminar drains between the third and seventh postoperative *** addition,a lower incidence of discomfort and of contamination with bacteria of a more pathogenic profile was observed in the patients with the silicone channeled ***:The silicone channeled drain was more comfortable and had less chance of occlusion,which is important in the detection of delayed dehiscence.

关键词： Bariatric surgery Contamination Drains Gastric leak Patency Peritonitis

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The Colíder Paleoproterozoic felsic volcanism:New insights into stratigraphy and petrogenesis in the southern Amazonian Craton

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Geoscience Frontiers 2024年第2期15卷 274-303页

作者： André Massanobu Ueno Kunifoshita Felipe Holanda dos santos Maria joséMesquita Instituto de Geociências Universidade Estadual de Campinas(UNICAMP)Rua Carlos Gomes250CEP:13083-855 CampinasSão PauloBrazil Departamento de Geologia Universidade Federal do CearáCampus do PiciBloco 912CEP:60440-554 FortalezaCearáBrazi

The eastern side of Alta Floresta Mineral Province(AFMP)(União do Norte region)comprises an effusive/-subvolcanic phase,explosive phase,and epiclastic *** effusive/subvolcanic phase comprises massive porphyritic rhyolite with different degrees of crystallinity,porphyritic rhyolite with flow structure,and microcrystalline *** explosive phase is characterized by welded lapilli tuff,lapilli tuff with flow structure,stratified lapilli tuff,and tuff with accretionary *** and siltstones characterize epiclastic *** are porphyritic rhyolite dikes that cut the volcanic *** rocks of the Colíder Group are rhyolites(>70%Sio2)with calcic-alkaline to alkaline-calcic affinity.A rhyolitic rock is predominantly ferroan and metaluminous,while a pyroclastic rock is predominantly magnesian to ferroan and meta-to peraluminous in *** rocks have a high LREE content,and slight fractionation of HREE suggests they have hybrid geochemical characteristics of high potassium calc-alkaline,shoshonitic,and suggestive affinities of A-type magmas,probably produced in a post-collisional orogenic *** rocks have a relatively high level of Ba and Rb and a negative anomaly for Sr,P,Nb,Ta,and Ti,suggesting an intra-plate mantle source with contributions from a metasomatized mantle *** rocks do not have adakitic characteristics nor fertility for Cu-Au(Sr/Yother regions of the *** welded lapilli tuff rocks show U-Pb age of 1838±17 Ma and 1817±2 Ma and are the older explosive *** effusive/subvolcanic phase has U-Pb ages of 1800±3 Ma and 1792±3 Ma obtained in the massive porphyritic *** age interval of approximately 46 Ma(1838–1792 Ma)suggests the presence of two or more volcanic cycles or distinct volcanic *** on the interpretation of volcanic and epiclastic deposits and remote sensing products,the paleoenvironmental reconstruction includes subaerial with effusive/subvolcani

关键词： Paleoproterozoic volcanism Eroded volcanic caldera Lithofacies analysis Colíder Group Amazonian Craton

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Adjuvant therapy for gastric cancer:What have we learned since INT0116?

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World Journal of Gastroenterology 2015年第13期21卷 3850-3859页

作者： Alexandre A Jácome Ajith K Sankarankutty josé sebastiao dos santos Department of Medical oncology Hospital Mater DeiBelo Horizonte 30190-131Minas GeraisBrazil Department of Surgery and Anatomy University of Sao Paulo at Ribeirao PretoSchool of MedicineRibeirao Preto14049-900Sao PauloBrazil

Gastric cancer is one of the main cancer-related causes of death worldwide. The curative treatment of gastric cancer consists of tumor resection and lymphadenectomy. However, surgical treatment alone is associated with high recurrence rates. Adjuvant treatment strategies have been studied over the last decades, but there have been controversial results from the initial studies. The pivotal INT0116 study demonstrated that the use of adjuvant chemoradiotherapy with 5-fluorouracil increases relapse-free and overall survival, and it has been adopted across the Western world. The high toxicity of radiochemotherapy and suboptimal surgical treatment employed, with fewer than 10% of the patients submitted to D2 lymphadenectomy, were the main study limitations. Since its publication, other adjuvant treatment modalities have been studied, and radiochemotherapy is being refined to improve its efficacy and safety. A multimodal approach has been demonstrated to significantly increase relapsefree and overall survival, and it can be offered in the form of perioperative chemotherapy, adjuvant chemoradiotherapy or adjuvant chemotherapy, regardless of the extent of lymphadenectomy. The objective of the present review is to report the major advances obtained in the last decades in the adjuvant treatment of gastric cancer as well as the perspectives of treatment based on recent knowledge of the molecular biology of the disease.

关键词： Stomach neoplasms Adjuvant radiotherapy Adjuvant chemotherapy Histology Genes erbB-2

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Evaluation and modeling of runoff and sediment yield for different land covers under simulated rain in a semiarid region of Brazil

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International Journal of Sediment Research 2018年第2期33卷 117-125页

作者： Richarde Marques da Silva Celso Augusto Guimares santos josé Yure Gomes dos santos Department of Geosaences Federal University of Paraíba Department of Civil and Environmental Engineering Federal University of Paraíba Federal University of Western Bahia Center for Humanities

This paper quantifies the runoff and sediment yield for four different land covers in a semiarid region of Brazil. The WESP model, a distributed, event-oriented runoff-erosion model, was applied and its physical parameters, NSand KR, were adjusted based on observed runoff and sediment yield data using simulated rainfall with an average intensity of 53 mm h-1. The sediment yield obtained was 53.02 kg ha-1(caatinga vegetation), 231.96 kg ha-1(bare soil), 309.75 kg ha-1(beans), and 847.38 kg ha-1(corn). The results showed that caatinga cover yields the lowest erosion and runoff when compared to the other *** results also show that the sediment yield and runoff values simulated with NS, KI, and KR parameters were well calibrated, within acceptable deviations. The caatinga vegetation was more effective in protecting the soil, when compared to the other types of coverage. The beans and corn covers had the highest values of runoff and sediment yield, even higher than those observed for bare soil.

关键词： Runoff Erosion Semiarid region WESP model

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Autophagy, apoptosis and organelle features during cell exposure to cadmiumč

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BIoCELL 2013年第2期37卷 45-54页

作者： CRISTIANE dos santos VERGILIo EDÉSIo josÉTENÓRIo DE MELo Universidade Estadual do Norte Fluminense Centro de Biociências e BiotecnologiaLaboratório de Biologia Celular e TecidualCampos dos GoytacazesRJBrasil28013-602.

Cadmium(Cd)induces several effects in different tissues,but our knowledge of the toxic effects on organelles is insuffi *** observe the progression of Cd effects on organelle structure and function,HuH-7 cells(human hepatic carcinoma cell line)were exposed to CdCl2 in increasing concentrations(1μM–20μM)and exposure times(2 h–24 h).During Cd treatment,the cells exhibited a progressive decrease in viability that was both time-and *** treated cells displayed progressive morphological changes that included cytoplasm retraction and nuclear condensation preceding a total loss of cell *** with 10μM for 12 h led to irreversible *** these drastic and irreparable damages,treated cells(5μM for 12 h)presented a progressive loss of mitochondrial function and cytoplasm acidifi cation as well as dysfunction and disorganization of microfi laments and endoplasmic *** damages led to the induction of apoptotic events and an increase in autophagic bodies in the *** results revealed that Cd affects multiple intra-cellular targets that induce alterations in the mitochondria,cytoskeleton,endoplasmic reticulum and acidic compartments,ultimately culminating in cell death via apoptotic and autophagic pathways.

关键词： Cd cell death hepatocyte HuH-7 cells mitochondria

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Gain of transcription factor binding sites is associated to changes in the expression signature of human brain and testis and is correlated to genes with higher expression breadth

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Science China(Life Sciences) 2019年第4期62卷 526-534页

作者： Vandeclécio Lira da Silva André Mauricio Ribeiro dos santos Wilfredo Blanco Sandro josé de Souza Bioinformatics Multidisciplinary Environment (BioME) Universidade Federal do Rio Grande do Norte (UFRN) Programa de Pós-Gradua??o em Genética e Biologia Molecular (PPGBM) Universidade Federal do Pará (UFPA) Department of Computer Science Universidade Estadual do Rio Grande do Norte (UERN) Brain Institute Universidade Federal do Rio Grande do Norte (UFRN)

The gain of transcription factor binding sites(TFBS) is believed to represent one of the major causes of biological *** we used strategies based on comparative genomics to identify 21,822 TFBS specific to the human lineage(TFBS-HS),when compared to chimpanzee and gorilla genomes. More than 40%(9,206) of these TFBS-HS are in the vicinity of 1,283 genes.A comparison of the expression pattern of these genes and the corresponding orthologs in chimpanzee and gorilla identified genes differentially expressed in human tissues. These genes show a more divergent expression pattern in the human testis and brain, suggesting a role for positive selection in the fixation of TFBS gains. Genes associated with TFBS-HS were enriched in gene ontology categories related to transcriptional regulation, signaling, differentiation/development and nervous ***, genes associated with TFBS-HS present a higher expression breadth when compared to genes in general. This biased distribution is due to a preferential gain of TFBS in genes with higher expression breadth rather than a shift in the expression pattern after the gain of TFBS.

关键词： TFBS transcript factor human evolution expression breadth

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Soil properties characterization for land-use planning and soil management in watersheds under family farming

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International Soil and Water Conservation Research 2022年第1期10卷 119-128页

作者： jose Miguel Reichert Paulo Ivonir Gubiani Danilo Rheinheimer dos santos Dalvan jose Reinert Celso Aita Sandro jose Giacomini Soils Department Universidade Federal de Santa Maria(UFSM)Santa MariaRSBrazil

Environmental monitoring of small,rural watersheds was one of the components of the Natural Re-sources Management and Rural Poverty Alleviation Program(RS-Rural)in southern *** purpose of the monitoring was to assess the impact of promoting soil conservation and environment manage-ment practices adopted by farmers and funded by the *** four small monitored watersheds,in a total of 95 plots representing distinct land use and soil management,surface soil was collected to characterize ground-zero of the Program by determining several soil physical,chemical and microbio-logical *** component analysis(PCA)shows soil physical,chemical and biological properties were decisive in defining the agricultural soils in the rural watersheds with family *** sensitivity to chemical properties provides an opportunity to improve soil quality if soil management focuses on altering those *** management practiced by tobacco farmers leads to rapid,intense degradation of some natural soil properties,especially those related to the dynamics of soil organic matter,compared with more conservationist uses(forest,regrowth,and grassland).Thus,soil management must be reoriented to avoid the progress of degradation and recover soil physical and biological *** crops and by land-abandonment to allow natural vegetation are important management strategies for the degraded soils used for tobacco production,increasing soil organic matter,nutrients and microbial activity and thus allowing further crop *** conclusion,wa-tersheds with tobacco cropping have soils with lower quality than when under no-tillage grain pro-duction,requiring changes in land use and soil management.

关键词： Natural resources management Environmental monitoring Soil conservation Soil quality Alleviating poverty

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Dealing with Multisource Information for Estuarine Flood Risk Appraisal in Two Western European Coastal Areas

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International Journal of Disaster Risk Science 2022年第2期13卷 199-213页

作者： Ana Rodrigues Rilo Alexandre Manuel de oliveira Soares Tavares Paula Maria dos santos Freire josé Luis Zêzere Estuarine and Coastal Zones Unit LNEC-National Civil Engineering Laboratory.1700-075 LisbonPortugal Centre of Geographical Studies Institute of Geography and Spatial PlanningUniversidade de Lisboa1700-066 LisbonPortugal Centre for Social Studies and Earth Sciences Department Coimbra University3030-790 CoimbraPortugal

Estuaries are usually affected by compound flooding triggers that cause diverse territorial *** fluvial flood risk assessment frameworks are well established in the literature,integrated management instruments that deal with estuarine flood risk remain incomplete and often *** research presents a methodology to extract relevant information from multiple sources post-event and a database building process that is applied to two contrasting estuaries(the Tagus River estuary in Portugal,and the Shannon River estuary in Ireland)in the Western European coastal ***,a total of 274 documents were analyzed and the information was stored in two *** correspondence analysis was applied to extract the most informative and relevant estuarine flood *** integrated estuarine flood risk assessment framework is presented and discussed based on the extracted *** framework is driven by two distinct dimensions(oceanic and hydrographic)and revealed the transversal position of triggers of estuarine floods,reflecting the compounding effects usually present in these *** results also highlight two levels of flood risk mostly based on damage typology.

关键词： Estuarine floods Estuarine flood indicators Multiple correspondence analysis Post-hazard multisource information Western Europe

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