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1.
Rev Esp Enferm Dig ; 115(11): 636-643, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37906059

RESUMO

INTRODUCTION: the COVID-19 pandemic had a strong impact on the healthcare model. The Sociedad Española de Patología Digestiva (SEPD) offered gastroenterology care units (UAAD) an instrument (EFIC_AD) to record and analyze their efficacy and efficiency. Thus, the impact of the pandemic on the activity of UAAD was assessed. METHODS: A descriptive study, based on the EFIC_AD registry for the period 2019-2021, of activity regarding admissions, clinic visits, and endoscopic as well as non-endoscopic tests, and endoscopy room performance. RESULTS: data were collected from up to 42 hospitals (22 with ≥ 500 beds). Overall, activity during 2020 compared to 2019 decreased by 12.30 % for admissions and 40 % for pH-metries (16.70 % for new clinic visits; 14.34 % for referrals from primary care; 24.70 % for gastroscopies; 32.50 % for colonoscopies; 31.00 % for endoscopic ultrasounds; 18.20 % for endoscopic retrograde cholangiopancreatography (ERCPs); 38.00 % for manometries; 23.60 % for abdominal ultrasounds; 36.17 % for liver transient elastographies [Fibroscan®]). The levels achieved during 2019 were not fully recovered during 2021 except for digestive motility studies, and virtually for endoscopy room performance rate (88.15 % in 2019; 67.77 % in 2020; 85.93 % in 2021). CONCLUSIONS: during 2020 the COVID-19 pandemic led to a markedly decreased in specific activities at UAAD, which was not fully recovered in 2021 despite endoscopy room performance return to normal.


Assuntos
COVID-19 , Gastroenterologia , Humanos , Pandemias , Endoscopia Gastrointestinal , Colonoscopia
2.
Heliyon ; 9(5): e16029, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37206048

RESUMO

The present study aims to elaborate a hydrogeological characterisation in the Water Sowing and Harvesting context. The study is focused on rural parishes in the Ecuadorian Andes that, despite their proximity to snow sources (Chimborazo glaciers), need more supply of this resource, to satisfy the demand of a population of 70,466 inhabitants. The study is based on hydrology and geomorphological analysis, a geophysical exploration, and a definition of water management strategies. The application of non-destructive geophysical methods and Geographic Information Systems support the hydrogeological study and the proposal of strategies for sustainable water management on the slopes of the Chimborazo volcano. An aquifer potential was identified (sand, gravel and fractured porphyritic andesites) with resistivity values between 51.3 and 157 Ω m at an approximate depth of 30 m from the geophysical characterisation addressed. This potential saturated zone is on the southern slope of the Chimborazo volcano within the hydrographic watershed, with favourable drainage networks for water accumulation. The aquifer shows a high-water saturation level but uncontrolled losses. As a consequence of these characteristics, alternatives for managing water resources are proposed, such as wells construction, using Water Sowing and Harvesting system methods ("camellones") based on Nature-Based Solutions, dam construction and environmental education. The different proposals are associated with the four sustainability axes of Brundtland (economic, social, environmental and cultural axis) and contribute to the sixth objective of the Sustainable Development Goal 2030 Agenda.

3.
Artigo em Inglês | MEDLINE | ID: mdl-35805816

RESUMO

Mineral resource exploitation is one of the activities that contribute to economic growth and the development of society. Artisanal and small-scale mining (ASM) is one of these activities. Unfortunately, there is no clear consensus to define ASM. However, its importance is relevant in that it represents, in some cases, the only employment alternative for millions of people, although it also significantly impacts the environment. This work aims to investigate the scientific information related to ASM through a bibliometric analysis and, in addition, to define the new lines that are tending to this field. The study comprises three phases of work: (i) data collection, (ii) data processing and software selection, and (iii) data interpretation. The results reflect that the study on ASM developed intensively from 2010 to the present. In general terms, the research addressed focuses on four interrelated lines: (i) social conditioning factors of ASM, (ii) environmental impacts generated by ASM, (iii) mercury contamination and its implication on health and the environment, and (iv) ASM as a livelihood. The work also defines that geotourism in artisanal mining areas is a significant trend of the last decade, explicitly focusing on the conservation and use of the geological and mining heritage and, in addition, the promotion of sustainable development of ASM.


Assuntos
Ouro , Mercúrio , Bibliometria , Geologia , Humanos , Mercúrio/análise , Mineração
4.
Rev Esp Enferm Dig ; 114(7): 375-389, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35686480

RESUMO

INTRODUCTION: there is limited experience and understanding of massive nonvariceal gastrointestinal bleeding during therapy with direct-acting oral anticoagulants. OBJECTIVES: to provide evidenced-based definitions and recommendations. METHODS: a consensus document developed by the Spanish Society of Digestives Diseases and the Spanish Society of Thrombosis and Haemostasis using modified Delphi methodology. A panel was set up of 24 gastroenterologists with experience in gastrointestinal bleeding, and consensus building was assessed over three rounds. Final recommendations are based on a systematic review of the literature using the GRADE system. RESULTS: panelist agreement was 91.53 % for all 30 items as a group, a percentage that was improved during rounds 2 and 3 for items where clinical experience is lower. Explicit disagreement was only 1.25 %. A definition of massive nonvariceal gastrointestinal bleeding in patients on direct-acting oral anticoagulants was established, and recommendations to optimize this condition's management were developed. CONCLUSION: the approach to these critically ill patients must be multidisciplinary and protocolized, optimizing decisions for an early identification of the condition and patient stabilization according to the tenets of damage control resuscitation. Thus, consideration must be given to immediate anticoagulation reversal, preferentially with specific antidotes (idarucizumab for dabigatran and andexanet alfa for direct factor Xa inhibitors); hemostatic resuscitation, and bleeding point identification and management.


Assuntos
Inibidores do Fator Xa , Trombose , Administração Oral , Anticoagulantes/efeitos adversos , Consenso , Hemorragia Gastrointestinal/tratamento farmacológico , Hemostasia , Humanos , Proteínas Recombinantes , Trombose/tratamento farmacológico
5.
Artigo em Inglês | MEDLINE | ID: mdl-34574372

RESUMO

Landslides are generated by natural causes and by human action, causing various geomorphological changes as well as physical and socioeconomic loss of the environment and human life. The study, characterization and implementation of techniques are essential to reduce land vulnerability, different socioeconomic sector susceptibility and actions to guarantee better slope stability with a significant positive impact on society. The aim of this work is the bibliometric analysis of the different types of landslides that the United States Geological Survey (USGS) emphasizes, through the SCOPUS database and the VOSviewer software version 1.6.17, for the analysis of their structure, scientific production, and the close relationship with several scientific fields and its trends. The methodology focuses on: (i) search criteria; (ii) data extraction and cleaning; (iii) generation of graphs and bibliometric mapping; and (iv) analysis of results and possible trends. The study and analysis of landslides are in a period of exponential growth, focusing mainly on techniques and solutions for the stabilization, prevention, and categorization of the most susceptible hillslope sectors. Therefore, this research field has the full collaboration of various authors and places a significant focus on the conceptual evolution of the landslide science.


Assuntos
Deslizamentos de Terra , Sistemas de Informação Geográfica , Geologia , Humanos
6.
United European Gastroenterol J ; 6(10): 1527-1537, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30574323

RESUMO

BACKGROUND: The diagnostic yield of the faecal immunochemical test and sigmoidoscopy in detecting proximal serrated polyps in a colorectal cancer screening programme has not been fully assessed. AIM: We determined the detection rate of proximal serrated polyps by simulated sigmoidoscopy and faecal immunochemical test compared with total colonoscopy in a population-based, multicentre, nationwide, randomised controlled trial (ColonPrev study). METHODS: Sigmoidoscopy yield was simulated based on the UK-Flexible Sigmoidoscopy Trial for total colonoscopy referral. Definitions were: proximal serrated polyp (proximal serrated polyp): sessile serrated polyp or hyperplastic polyp of any size and proximal at-risk serrated polyp (at-risk proximal serrated polyp): sessile serrated polyp of any size or hyperplastic polyp ≥ 10 mm, both located proximally to the splenic flexure. RESULTS: A total of 10,611 individuals underwent faecal immunochemical test and 5059 underwent total colonoscopy and were evaluated by simulated sigmoidoscopy. Sigmoidoscopy and faecal immunochemical test were less accurate in detecting proximal serrated polyps (odds ratio: 0.13; 95% confidence interval: 0.10-0.18 and 0.13; 0.09-0.18, p < 0.0001, respectively). Both tests were inferior to colonoscopy in detecting at-risk proximal serrated polyps, and sigmoidoscopy was inferior to faecal immunochemical test in detecting these lesions (odds ratio: 0.17; 95% confidence interval: 0.10-0.30 and 0.25; 0.17-0.37, p < 0.0001, respectively). CONCLUSION: Sigmoidoscopy and faecal immunochemical test are less accurate in detecting proximal serrated polyps than colonoscopy, particularly in women.

7.
Rev Esp Enferm Dig ; 110(1): 44-50, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29284269

RESUMO

OBJECTIVES: To reach a situation diagnosis on the status of patient management at digestive care units (DCUs) in Spain. MATERIAL AND METHODS: A cross-sectional descriptive study across DCUs in general acute care hospitals within the Spanish National Health System (data referred to 2015). The study variables were collected with a questionnaire including items on structure, services portfolio, activity, education, research, and good practice. Hospital discharge rates for digestive diseases were also assessed using the minimum basic data set (2005-2014). RESULTS: Two hundred and nine hospitals invited, 55 responders (26.3%). Average discharges from hospital were 1,139 ± 653 per DCU/year, and 100 ± 66 per year per dedicated gastroenterologist. In 2014, admission rate to DCUs per 1,000 population and year was 280, with a mean stay of 7.4 days. The analysis of the MBDS for 2005-2014 reveals a progressive increase in the number of discharges (37% more in 2014 versus 2005), with a 28% decrease in hospital gross mortality rate (3.7% in 2014) and a slightly reduced (14%) mean stay (7.6 days in 2014). Considerable variability may be seen in structure, activity, and results indicators. Mortality and readmission rates, as well as mean stay, vary more than 100% amongst DCUs, and major dispersions also exist in frequentation and results amongst autonomous communities. CONCLUSIONS: The RECALAD 2015 survey unveiled relevant aspects related to DCUs organization, structure, and management. The notable variability encountered likely reflects relevant differences in efficiency and productivity, and thus points out there is ample room for improvement.


Assuntos
Doenças do Sistema Digestório/terapia , Estudos Transversais , Atenção à Saúde , Doenças do Sistema Digestório/epidemiologia , Pesquisas sobre Atenção à Saúde , Unidades Hospitalares/estatística & dados numéricos , Humanos , Projetos Piloto , Espanha/epidemiologia
8.
United European Gastroenterol J ; 5(2): 255-260, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28344793

RESUMO

BACKGROUND: The adenoma detection rate (ADR) is the main quality indicator of colonoscopy. The ADR recommended in fecal immunochemical testing (FIT)-based colorectal cancer screening programs is unknown. METHODS: Using the COLONPREV (NCT00906997) study dataset, we performed a post-hoc analysis to determine if there was a correlation between the ADR in primary and work-up colonoscopy, and the equivalent figure to the minimal 20% ADR recommended. Colonoscopy was performed in 5722 individuals: 5059 as primary strategy and 663 after a positive FIT result (OC-Sensor™; cut-off level 15 µg/g of feces). We developed a predictive model based on a multivariable lineal regression analysis including confounding variables. RESULTS: The median ADR was 31% (range, 14%-51%) in the colonoscopy group and 55% (range, 21%-83%) in the FIT group. There was a positive correlation in the ADR between primary and work-up colonoscopy (Pearson's coefficient 0.716; p < 0.001). ADR in the FIT group was independently related to ADR in the colonoscopy group: regression coefficient for colonoscopy ADR, 0.71 (p = 0.009); sex, 0.09 (p = 0.09); age, 0.3 (p = 0.5); and region 0.00 (p = 0.9). The equivalent figure to the 20% ADR was 45% (95% confidence interval, 35%-56%). CONCLUSIONS: ADR in primary and work-up colonoscopy of a FIT-positive result are positively and significantly correlated.

9.
Microbiol Immunol ; 60(11): 787-792, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27797112

RESUMO

Immunological molecules are implicated in inflammatory disorders, including inflammatory bowel disease (IBD; Crohn disease [CD] and ulcerative colitis [UC]). Killer cell immunoglobulin-like receptors (KIRs) are also genetically variable proteins involved in immune function. They are expressed by NK cells and certain T lymphocytes, regulate specificity and function by interaction with HLA Class I molecules, may be either inhibitory or activating and are polymorphic both in terms of alleles and haplotype gene content. Genetic associations between activating KIRs and certain autoimmune and inflammatory diseases have been reported; however, a possible association between KIR and IBD remains unclear. The aim of this study was to determine the relationship between KIR repertoire and IBD pathologies in a Spanish cohort. KIR variability was analyzed using PCR-sequence specific oligonucleotide probes (SSOP). Inhibitory KIR2DL5 was found more frequently in UC and IBD patient groups than in healthy controls (P = 0.028 and P = 0.01, respectively), as was activating KIR2DS1 (P = 0.02, Pc > 0.05, UC vs. Controls; P = 0.001, Pc = 0.01, IBD vs Controls; P = 0.01, Pc > 0.05, Controls vs CR), KIR2DS5 (P = 0.0028, Pc = 0.04, Controls vs UC; P = 0.0001, Pc = 0.0017, Controls vs IBD; P = 0.01, Pc > 0.05, Controls vs CD) and KIR3DS1 (P = 0.012, Pc > 0.05, Controls vs IBD). Our data suggest that imbalance between activating and inhibitory KIR may partially explain the different pathogeneses of these IBDs and that there is a hypothetical role for the telomeric B region (which contains both KIR2DS5 and KIR2DS1) in these diseases.


Assuntos
Variação Genética , Doenças Inflamatórias Intestinais/genética , Receptores KIR/genética , População Branca/genética , Adolescente , Adulto , Alelos , Criança , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Genótipo , Antígenos HLA-C/genética , Antígenos HLA-C/imunologia , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/imunologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Masculino , Pessoa de Meia-Idade , Espanha , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Adulto Jovem
10.
Endoscopy ; 48(11): 995-1002, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27485482

RESUMO

Background and study aims: The European guidelines for quality assurance in colorectal cancer (CRC) screening have established high-risk (≥ 5 adenomas or an adenoma ≥ 20 mm) and intermediate-risk (3 - 4 adenomas or at least one adenoma 10 - 19 mm in size, or villous histology, or high grade dysplasia) groups with different endoscopic surveillance intervals. The aim of this study was to evaluate the difference in the incidence of advanced neoplasia (advanced adenoma or CRC) between the two risk groups. Patients and methods: This retrospective group study included patients meeting high- or intermediate-risk criteria for adenomas detected in CRC screening programs and the COLONPREV study before European guidelines were adopted in Spain (June 2011) with a 3-year surveillance recommendation according to Spanish guidelines. The primary outcome measure was the incidence of advanced neoplasia in patients undergoing surveillance. The secondary outcome measure was the CRC incidence. We used an adjusted proportional hazards regression model to control confounding variables. Results: The study included 5401 patients (3379 intermediate risk, 2022 high risk). Endoscopic surveillance was performed in 65.5 % of the patients (2.8 ±â€Š1 years). The incidence of advanced neoplasia in the high- and intermediate-risk groups was 16.0 % (59.0 cases/1000 patient-years) and 12.3 % (41.2 cases/1000 patient-years), respectively. The CRC incidence was 0.5 % (1.4 cases/1000 patient-years) and 0.4 % (1 case/1000 patient-years), respectively. The advanced neoplasia and CRC attributable risk to the high risk group was of 3.7 % and 0.1 %, respectively. In the proportional hazards analysis, the risk of advanced neoplasia was greater in the high-risk group (hazard ratio [HR] 1.5, 95 % confidence interval [CI] 1.2 - 1.8), with no significant differences in the CRC incidence (HR 1.6, 95 %CI 0.6 - 3.8). Conclusions: Patients meeting high-risk criteria have a higher incidence of advanced neoplasia during endoscopic surveillance. No differences were found in the CRC incidence at a 3-year surveillance recommendation.


Assuntos
Adenoma/epidemiologia , Adenoma/patologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Sangue Oculto , Vigilância da População , Idoso , Colonoscopia , Detecção Precoce de Câncer/normas , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Fatores de Risco , Espanha/epidemiologia , Carga Tumoral
11.
Dig Liver Dis ; 48(5): 542-551, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26936343

RESUMO

BACKGROUND: There is no information on the impact of age and gender on the diagnostic yield of different positivity thresholds for the fecal immunochemical test for hemoglobin (FIT). OBJECTIVES: To evaluate the performance of this test at distinct positivity cut-offs in a population-based colorectal cancer (CRC) screening program. METHODS: CRC detection rate (DR), and analysis of resources were evaluated retrospectively, at different cut-offs of FIT (20, 25, 30, 35 and 40µg Hb/g) respect to a reference value (15µg Hb/g), according to age and gender, in a screening population of 10,611 participants of the ColonPrev study (Quintero. NEJM 2013). RESULTS: At the reference cut-off value, 36 CRC and 252 advanced adenomas (AA) were diagnosed. Increasing the cut-off in women ≤60 years decreases colonoscopies performed by 44.5% without modifying the CRC (DR). Same CRC DR was observed in men ≤60 years and women >60 years increasing cut-off at 25-30µg Hb/g. In men >60 years, all increases in the cut-off affected the CRC DR, especially when the cut-off was increased from 35 to 40µg Hb/g (CRC miss rate 25%). CONCLUSIONS: To improve the performance of FIT in CRC screening programs, FIT cut-offs could be individualized by age and gender.


Assuntos
Adenoma/diagnóstico , Carcinoma in Situ/diagnóstico , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Fezes/química , Hemoglobinas/análise , Fatores Etários , Idoso , Colonoscopia , Feminino , Humanos , Imunoensaio , Imunoquímica , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Ensaios Clínicos Controlados Aleatórios como Assunto , Valores de Referência , Estudos Retrospectivos , Fatores Sexuais
12.
Rev Esp Enferm Dig ; 107(9): 554-8, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26334462

RESUMO

INTRODUCTION AND AIMS: The understanding of lactose intolerance (LI) is limited in some professional settings. Sociedad Española de Patología Digestiva (SEPD) and Sociedad Española de Medicina General (SEMG) have developed a survey in order to: a) Analyze primary care physicians (PCPs) knowledge and clinical management; and b) to compare results with those of a previous survey of Spanish gastroenterologists (GEs). MATERIAL AND METHODS: An online questionnaire was sent to SEMG members with 27 items on various issues: Demographics, occupational characteristics, outlook on LI, diagnostic tests, treatment, and follow-up. Results were compared to those from a survey of GEs. RESULTS: A total of 456 PCPs responded, versus 477 GEs. PCPs had an older mean age and longer professional experience. Level of understanding of LI was similar, albeit a higher proportion of PCPs lacked epidemiological awareness (p < 0.01). GEs tended to consider LI a "minor" condition (71.3 vs. 40.1%; p > 0.001), and LI symptoms as overlapping those of irritable bowel syndrome (93.5 vs. 88.2%; p = 0.005), although symptoms perceived as suspicious of LI were similar in both groups. Dietary recommendations were recognized as the primary therapeutic approach. CONCLUSION: This study reveals the outlook of PCPs on LI, and allows comparison with that of GEs, as a basis for the development of strategies aimed at improving LI understanding, approach and management in our setting.


Assuntos
Gastroenterologistas , Intolerância à Lactose/terapia , Médicos de Atenção Primária , Adulto , Idoso , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Intolerância à Lactose/dietoterapia , Masculino , Pessoa de Meia-Idade , Médicos , Espanha/epidemiologia , Inquéritos e Questionários
13.
Int J Colorectal Dis ; 30(10): 1407-16, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26179377

RESUMO

PURPOSE: The purpose of this study is to compare the efficacy and acceptability of an evening-before regimens of sodium picosulfate/magnesium citrate (SPMC) and polyethylene glycol (PEG) as bowel cleansers and to explore the results of a same-day regimen of SPMC. METHODS: Multicenter, randomized, observer-blinded, parallel study carried out in subjects who were 18-80 years old and were undergoing diagnostic colonoscopy for the first time. The primary outcome was treatment success, which was a composite outcome defined by (1) the evaluation of the overall preparation quality as "excellent" or "good" by two blinded independent evaluators with the Fleet(®) Grading Scale for Bowel Cleansing and (2) a subject's acceptability rating of "easy to take" or "tolerable." The primary outcome was analyzed using a logistic regression with site, gender, and age group (age ≥65 years and <65 years) as factors. RESULTS: Four hundred ninety subjects were included in the efficacy evaluation. Although treatment success was significantly higher in subjects assigned to the evening-before regimen of SPMC vs. subjects assigned to the evening-before PEG, when evaluating the two individual components for treatment success, there were significant differences in the ease of completion but not in the quality of preparation. The same-day SPMC regimen was superior to both the evening-before regimen of SPMC and PEG in terms of the quality of preparation, especially regarding the proximal colon. CONCLUSIONS: An evening-before regimen of SPMC is superior to an evening-before regimen of PEG in terms of subject's acceptability. The same-day SPMC regimen provides better cleansing levels in the proximal colon.


Assuntos
Catárticos , Citratos , Ácido Cítrico , Colonoscopia/métodos , Compostos Organometálicos , Satisfação do Paciente , Picolinas , Polietilenoglicóis , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Catárticos/administração & dosagem , Catárticos/efeitos adversos , Citratos/administração & dosagem , Citratos/efeitos adversos , Ácido Cítrico/administração & dosagem , Ácido Cítrico/efeitos adversos , Esquema de Medicação , Feminino , Gastroenteropatias/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/efeitos adversos , Picolinas/administração & dosagem , Picolinas/efeitos adversos , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Adulto Jovem
14.
Transl Res ; 166(2): 196-206, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25795236

RESUMO

The identification of tumor cells in lymph nodes is essential for the correct classification of patients with colorectal cancer who may benefit from adjuvant treatments. Proper classification of tumor stage becomes entangled by variables such as an insufficient number of lymph nodes examined, which can result in erroneous or missed diagnosis. The determination of pathologic factors in the primary tumor associated with positive lymph nodes is an area of research that has attempted to provide variables to solve this problem. In the present study, we observed that the localization of annexin A2 (AnxA2) in a cell membrane is the characteristic that distinguishes tumor cells with high invasiveness. Localization of AnxA2 expression was also studied in tissue specimens from 58 patients with invasive colorectal carcinoma (T3-T4), who had undergone colectomy with radical lymph node dissection. Interestingly, the membrane pattern observed in tumor cell lines was also identified in patient's tissue samples and allowed us to distinguish among different cell populations with the tumor. Univariate analysis showed that tumor deposits in pericolic fat, extramural vascular invasion, and amount of cells with AnxA2 membrane pattern in the tumor invasive edge had a significant influence on lymph node metastasis. On the contrary, multivariate analysis revealed that the number of cells with AnxA2 membrane pattern (P < 0.05) and tumor deposits (P < 0.05) was significantly associated with lymph node metastasis. Furthermore, AnxA2 cellular localization was observed in cell clusters that define tumor budding, and a significant association between both variables was detected.


Assuntos
Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Anexina A2/metabolismo , Membrana Celular/metabolismo , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Linfonodos/patologia , Idoso , Linhagem Celular Tumoral , Eletroforese em Gel Bidimensional , Feminino , Humanos , Linfonodos/metabolismo , Masculino , Invasividade Neoplásica , Transporte Proteico
16.
Transl Oncol ; 7(5): 590-604, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25389454

RESUMO

The use of heat shock protein 90 (Hsp90) inhibitors is an attractive antineoplastic therapy. We wanted to compare the effects of the benzoquinone 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin) and the novel isoxazole resorcinol-based Hsp90 inhibitor NVP-AUY922 in a panel of pancreatic and colorectal carcinoma cell lines and in colorectal primary cultures derived from tumors excised to patients. PANC-1, CFPAC-1, and Caco-2 cells were intrinsically resistant to 17-AAG but sensitive to NVP-AUY922. Other cellular models were sensitive to both inhibitors. Human epidermal growth factor receptor receptors and their downstream signaling pathways were downregulated in susceptible cellular models, and concurrently, Hsp70 was induced. Intrinsic resistance to 17-AAG did not correlate with expression of ATP-binding cassette transporters involved in multidrug resistance. Some 17-AAG-resistant, NVP-AUY922-sensitive cell lines lacked NAD(P)H: quinone oxidoreductase 1 (NQO1) enzyme and activity. However, colorectal LoVo cells still responded to both drugs in spite of having undetectable levels and activity of NQO1. Pharmacological and biologic inhibition of NQO1 did not confer resistance to 17-AAG in sensitive cell lines. Therefore, even though 17-AAG sensitivity is related to NQO1 protein levels and enzymatic activity, the absence of NQO1 does not necessarily convey resistance to 17-AAG in these cellular models. Moreover, NVP-AUY922 does not require NQO1 for its action and is a more potent inhibitor than 17-AAG in these cells. More importantly, we show in this report that NVP-AUY922 potentiates the inhibitory effects of chemotherapeutic agents, such as gemcitabine or oxaliplatin, and other drugs that are currently being evaluated in clinical trials as antitumor agents.

17.
Neoplasia ; 16(10): 845-60, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25379021

RESUMO

Selumetinib (AZD6244, ARRY-142886) is a MEK1/2 inhibitor that has gained interest as an anti-tumour agent. We have determined the degree of sensitivity/resistance to Selumetinib in a panel of colorectal cancer cell lines using cell proliferation and soft agar assays. Sensitive cell lines underwent G1 arrest, whereas Selumetinib had no effect on the cell cycle of resistant cells. Some of the resistant cell lines showed high levels of ERK1/2 phosphorylation in the absence of serum. Selumetinib inhibited phosphorylation of ERK1/2 and RSK and had no effect on AKT phosphorylation in both sensitive and resistant cells. Furthermore, mutations in KRAS, BRAF, or PIK3CA were not clearly associated with Selumetinib resistance. Surprisingly, Selumetinib was able to inhibit phosphorylation of p70 S6 kinase (p70S6K) and its downstream target ribosomal protein S6 (RPS6) in sensitive cell lines. However, p70S6K and RPS6 phosphorylation remained unaffected or even increased in resistant cells. Moreover, in some of the resistant cell lines p70S6K and RPS6 were phosphorylated in the absence of serum. Interestingly, colorectal primary cultures derived from tumours excised to patients exhibited the same behaviour than established cell lines. Pharmacological inhibition of p70S6K using the PI3K/mTOR inhibitor NVP-BEZ235, the specific mTOR inhibitor Rapamycin and the specific p70S6K inhibitor PF-4708671 potentiated Selumetinib effects in resistant cells. In addition, biological inhibition of p70S6K using siRNA rendered responsiveness to Selumetinib in resistant cell lines. Furthermore, combination of p70S6K silencing and PF-47086714 was even more effective. We can conclude that p70S6K and its downstream target RPS6 are potential biomarkers of resistance to Selumetinib in colorectal cancer.


Assuntos
Benzimidazóis/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Proteína S6 Ribossômica/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Classe I de Fosfatidilinositol 3-Quinases , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Ativação Enzimática/efeitos dos fármacos , Humanos , Imidazóis/farmacologia , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Terapia de Alvo Molecular , Mutação , Fosfatidilinositol 3-Quinases/genética , Fosforilação/efeitos dos fármacos , Piperazinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras) , Quinolinas/farmacologia , Proteínas Quinases S6 Ribossômicas 70-kDa/genética , Proteínas ras/genética
19.
Cancer Causes Control ; 25(8): 985-97, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24859111

RESUMO

PURPOSE: To compare two strategies for colorectal cancer screening: one-time colonoscopy versus fecal immunochemical testing (FIT) (and colonoscopy for positive) every 2 years, in order to determine which strategy provides the highest participation and detection rates in groups of sex and age. METHODS: This analysis was performed with data from the first screening round within the COLONPREV study, a population-based, multicenter, nationwide trial carried out in Spain. Several logistic regression models were applied to identify the influence of the screening test on participation rates and detection of proximal and distal neoplasms, as well to identify the influence of age and sex: women aged 50-59 years, women aged 60-69 years, men aged 50-59 years, and men aged 60-69 years. RESULTS: Participation was higher in women than in men, especially among women aged 50-59 years (25.91 % for colonoscopy and 35.81 % for FIT). Crossover from colonoscopy to FIT was higher among women than men, especially among those aged 60-69 years (30.37 %). In general, detection of any neoplasm and advanced adenoma was higher with colonoscopy than with FIT, but no significant differences were found between the two strategies for colorectal cancer detection. Detection of advanced adenoma in both arms was lower in women [specifically in women aged 50-59 years (OR 0.31; 95 % CI 0.25-0.38) than in men aged 60-69 years]. Women aged 50-59 years in the colonoscopy arm had a higher probability of detection of advanced adenoma (OR 4.49; 95 % CI 3.18-6.35), as well as of detection of neoplasms in proximal and distal locations (proximal OR 19.34; 95 % CI 12.07-31.00; distal OR 11.04; 95 % CI 8.13-15.01) than women of the same age in the FIT arm. These differences were also observed in the remaining groups but to a lesser extent. CONCLUSION: Women were more likely to participate in a FIT-based strategy, especially those aged 50-59 years. The likelihood of detection of any neoplasm was higher in the colonoscopy arm for all the population groups studied, especially in women aged 50-59 years. Distinct population groups should be informed of the benefits of each screening strategy so that they may take informed decisions.


Assuntos
Neoplasias Colorretais/diagnóstico , Fatores Etários , Idoso , Colonoscopia , Fezes/química , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Fatores Sexuais
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