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1.
Environ Res ; 246: 118164, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38211717

RESUMO

Biogas serves as a crucial renewable energy vector to ensure a more sustainable energy future. However, the presence of hydrogen sulfide (H2S) limits its application in various sectors, emphasizing the importance of effective H2S removal techniques for maximizing its potential. In the present study, the limits of a pilot-scale bioscrubber for biogas desulfurization was study in a real scenario. An increase in the superficial liquid velocity resulted in significant improvements in the H2S removal efficiency, increasing from 76 ± 8% (elimination capacity of 6.2 ± 0.5 gS-H2S m-3 h-1) to 97.7 ± 0.5% (elimination capacity of 8 ± 1 gS-H2S m-3 h-1) as the superficial liquid velocity increased from 50 ± 3 m h-1 to 200 ± 8 m h-1. A USL of 161.4 ± 0.5 m h-1 was able to achieve outlet H2S concentrations as low as 3 ± 1 ppmv (H2S removal efficiency of 97 ± 1%) for 7 days. High superficial liquid velocity favoured the aerobic H2S oxidation reducing the nitrate demand. The maximum EC reached throughout the operation was 50.8 ± 0.6 gS-H2S m-3 h-1 (H2S removal efficiency of 96 ± 1%) and a sulfur production of 60%. Studies in batch flocculation experiments showed sulfur removal rates up to 97.6 ± 0.9% with a cationic flocculant dose of 75 mg L-1. Microbial analysis revealed that the predominant genus with sulfo-oxidant capacity during periods of low H2S inlet load was Thioalkalispira-sulfurivermis (61-69%), while in periods of higher H2S inlet load, family Arcobacteraceae was the most prevalent (11%).


Assuntos
Reatores Biológicos , Sulfeto de Hidrogênio , Biocombustíveis , Enxofre , Instalações de Eliminação de Resíduos
2.
Clin Transl Oncol ; 24(3): 483-494, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34773566

RESUMO

5-Fluorouracil (5-FU) and oral fluoropyrimidines, such as capecitabine, are widely used in the treatment of cancer, especially gastrointestinal tumors and breast cancer, but their administration can produce serious and even lethal toxicity. This toxicity is often related to the partial or complete deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme, which causes a reduction in clearance and a longer half-life of 5-FU. It is advisable to determine if a DPD deficiency exists before administering these drugs by genotyping DPYD gene polymorphisms. The objective of this consensus of experts, in which representatives from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology participated, is to establish clear recommendations for the implementation of genotype and/or phenotype testing for DPD deficiency in patients who are candidates to receive fluoropyrimidines. The genotyping of DPYD previous to treatment classifies individuals as normal, intermediate, or poor metabolizers. Normal metabolizers do not require changes in the initial dose, intermediate metabolizers should start treatment with fluoropyrimidines at doses reduced to 50%, and poor metabolizers are contraindicated for fluoropyrimidines.


Assuntos
Capecitabina/uso terapêutico , Di-Hidrouracila Desidrogenase (NADP)/genética , Fluoruracila/uso terapêutico , Técnicas de Genotipagem/normas , Neoplasias/tratamento farmacológico , Neoplasias/genética , Seleção de Pacientes , Humanos , Polimorfismo de Nucleotídeo Único
3.
ESMO Open ; 6(4): 100215, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34325108

RESUMO

BACKGROUND: Young oncologists are at particular risk of professional burnout, and this could have a significant impact on their health and care of their patients. The coronavirus disease 2019 (COVID-19) pandemic has forced rapid changes in professionals' jobs and training, with the consequent physical and psychological effects. We aimed to characterize burnout levels and determinants in young oncologists, and the effects of the pandemic on their training and health. METHODS: Two online surveys were conducted among oncology residents and young oncology specialists in Spain. The first addressed professional burnout and its determinants before the COVID-19 pandemic, while the second analyzed the impact of the pandemic on health care organization, training, and physical and psychological health in the same population. RESULTS: In total, 243 respondents completed the first survey, and 263 the second; 25.1% reported significant levels of professional burnout. Burnout was more common among medical oncology residents (28.2%), mainly in their second year of training. It was significantly associated with a poor work-life balance, inadequate vacation time, and the burnout score. Nearly three-quarters of respondents (72%) were reassigned to COVID-19 care and 84.3% of residents missed part of their training rotations. Overall, 17.2% of this population reported that they had contracted COVID-19, 37.3% had scores indicating anxiety, and 30.4% moderate to severe depression. Almost a quarter of young oncologists (23.3%) had doubts about their medical vocation. CONCLUSIONS: Burnout affects a considerable number of young oncologists. The COVID-19 pandemic has had a profound impact on causes of burnout, making it even more necessary to periodically monitor it to define appropriate detection and prevention strategies.


Assuntos
Esgotamento Profissional , COVID-19 , Oncologistas , Esgotamento Profissional/epidemiologia , Esgotamento Psicológico/epidemiologia , Esgotamento Psicológico/prevenção & controle , Humanos , Oncologia , Pandemias , SARS-CoV-2
4.
Rev. argent. cir. plást ; 27(2): 90-95, 20210000. fig
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1357908

RESUMO

La metaplasia sinovial capsular mamaria es una patología poco frecuente, de origen desconocido, que se presenta generalmente con aumento de volumen mamario (colección líquida) en un período breve y frecuentemente unilateral el posoperatorio (3 meses o más). Su diagnóstico se realiza por punción con aguja fina guiada por ecografía y estudios histomorfológico y de inmunohistoquímica. Debe diferenciarse del linfoma anaplásico de células grandes asociado a implantes mamarios. El tratamiento consiste en extracción por punción de la colección líquida, reposo del brazo del lado afectado y en caso de recidivas cambio de implante e instilación de corticoides en bolsillo capsular. Presentación a propósito de un caso.


Breast capsular Synovial Metaplasia is a rare pathology of unknown origin, which usually occurs with increased breast volume (liquid collection) in a short and often unilateral postoperatively (3 months or more). Diagnosis is made with fine needle puncture guided by ultrasound and histomorphological and immunohistochemistry studies. It should differ from anaplastic large cell lymphoma associated with breast implants. Treatment consists of puncture extraction of the liquid collection, rest of the arm of the affected side and in case of relapses implant change and installation of Corticoids in capsular pocket. Filing on a case


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Reoperação , Drenagem , Implante Mamário , Metaplasia/patologia
8.
J Nucl Cardiol ; 27(4): 1274-1284, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-30977094

RESUMO

BACKGROUND: We evaluated the effect of cardiac resynchronization therapy (CRT) on septal perfusion and thickening at 6 months post implantation assessed on Tc99m-MIBI Gated myocardial perfusion SPECT (GMPS).We also studied the association of change in septal perfusion and thickening with primary outcome defined as at least one [improvement in ≥1NYHA class, left ventricular ejection fraction (LVEF) by ≥ 5%, reduction of end-systolic volume (ESV) by ≥ 15%, and improvement ≥ 5 points in Minnesota living with heart failure questionnaire (MLHFQ)]. METHOD: One hundred and five patients underwent clinical and GMPS evaluation before and at 6 months post CRT. RESULT: Post CRT there was significant improvement in mean normalized septal perfusion uptake and in septal thickening (P value = 0.001, both). There was no significant relation between improvement in septal perfusion and primary outcome. However, improvement in septal thickening was statistically significant with favorable primary outcome (P = 0.001).There was no significant correlation between improvement of septal perfusion and improvement in LVEF, reduction in End diastolic volume (EDV), ESV, and Left ventricular Dyssynchrony (LVD). But, there was significant correlation between improvement of septal thickening and these parameters. CONCLUSION: Improvement in septal thickening was associated with reverse remodeling, improvement in LVEF, and reduction of LVD.


Assuntos
Terapia de Ressincronização Cardíaca , Septos Cardíacos/patologia , Função Ventricular Esquerda/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão do Miocárdio , Estudos Prospectivos , Tecnécio Tc 99m Sestamibi , Tomografia Computadorizada de Emissão de Fóton Único , Adulto Jovem
9.
Eur J Nucl Med Mol Imaging ; 46(11): 2235-2243, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31367906

RESUMO

PURPOSE: Patients with stage III non-small-cell lung cancer (NSCLC) treated with chemoradiotherapy (CRT) in low- and middle-income countries (LMIC) continue to have a poor prognosis. It is known that FDG PET/CT improves staging, treatment selection and target volume delineation (TVD), and although its use has grown rapidly, it is still not widely available in LMIC. CRT is often used as sequential treatment, but is known to be more effective when given concurrently. The aim of the PERTAIN study was to assess the impact of introducing FDG PET/CT-guided concurrent CRT, supported by training and quality control (QC), on the overall survival (OS) and progression-free survival (PFS) of patients with stage III NSCLC. METHODS: The study included patients with stage III NSCLC from nine medical centres in seven countries. A retrospective cohort was managed according to local practices between January 2010 and July 2014, which involved only optional diagnostic FDG PET/CT for staging (not for TVD), followed by sequential or concurrent CRT. A prospective cohort between August 2015 and October 2018 was treated according to the study protocol including FDG PET/CT in treatment position for staging and multimodal TVD followed by concurrent CRT by specialists trained in protocol-specific TVD and with TVD QC. Kaplan-Meier analysis was used to assess OS and PFS in the retrospective and prospective cohorts. RESULTS: Guidelines for FDG PET/CT image acquisition and TVD were developed and published. All specialists involved in the PERTAIN study received training between June 2014 and May 2016. The PET/CT scanners used received EARL accreditation. In November 2018 a planned interim analysis was performed including 230 patients in the retrospective cohort with a median follow-up of 14 months and 128 patients in the prospective cohort, of whom 69 had a follow-up of at least 1 year. Using the Kaplan-Meier method, OS was significantly longer in the prospective cohort than in the retrospective cohort (23 vs. 14 months, p = 0.012). In addition, median PFS was significantly longer in the prospective cohort than in the retrospective cohort (17 vs. 11 months, p = 0.012). CONCLUSION: In the PERTAIN study, the preliminary results indicate that introducing FDG PET/CT-guided concurrent CRT for patients with stage III NSCLC in LMIC resulted in a significant improvement in OS and PFS. The final study results based on complete data are expected in 2020.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Quimiorradioterapia , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Carcinoma Pulmonar de Células não Pequenas/terapia , Intervalo Livre de Doença , Estônia , Feminino , Fluordesoxiglucose F18 , Humanos , Processamento de Imagem Assistida por Computador , Índia , Jordânia , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Paquistão , Estudos Prospectivos , Controle de Qualidade , Planejamento da Radioterapia Assistida por Computador , Estudos Retrospectivos , Resultado do Tratamento , Turquia , Vietnã
10.
Eur J Nucl Med Mol Imaging ; 46(10): 1990-2012, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31273437

RESUMO

PURPOSE: Single-photon emission computed tomography (SPECT) combined with computed tomography (CT) was introduced as a hybrid SPECT/CT imaging modality two decades ago. The main advantage of SPECT/CT is the increased specificity achieved through a more precise localization and characterization of functional findings. The improved diagnostic accuracy is also associated with greater diagnostic confidence and better inter-specialty communication. METHODS: This review presents a critical assessment of the relevant literature published so far on the role of SPECT/CT in a variety of clinical conditions. It also includes an update on the established evidence demonstrating both the advantages and limitations of this modality. CONCLUSIONS: For the majority of applications, SPECT/CT should be a routine imaging technique, fully integrated into the clinical decision-making process, including oncology, endocrinology, orthopaedics, paediatrics, and cardiology. Large-scale prospective studies are lacking, however, on the use of SPECT/CT in certain clinical domains such as neurology and lung disorders. The review also presents data on the complementary role of SPECT/CT with other imaging modalities and a comparative analysis, where available.


Assuntos
Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/métodos , Doenças Ósseas/diagnóstico por imagem , Doenças Cardiovasculares/diagnóstico por imagem , Humanos , Neoplasias/diagnóstico por imagem , Doenças do Sistema Nervoso/diagnóstico por imagem , Imagem de Perfusão/métodos , Imagem de Perfusão/normas , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/normas
11.
J Nucl Cardiol ; 26(6): 2048-2054, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31286416

RESUMO

Cardiovascular diseases (CVDs) are the leading cause of death in Latin America and the Caribbean (LAC) region as well as worldwide. Lifestyle, nutritional habits and the upsurge of obesity have contributed to the increase in the prevalence of CVDs in the region. The role of nuclear cardiology in the management of patients with CVDs is well established. Particularly, myocardial perfusion imaging is widely used in LAC countries and has been increasingly integrated into the healthcare systems in the region for the diagnosis of coronary artery disease, risk stratification and to guide patient management. In its role to support countries around the world to address their health needs through the peaceful applications of nuclear techniques, the International Atomic Energy Agency (IAEA) has provided assistance to the LAC region for the establishment and strengthening of the nuclear cardiology practice. To that extent, the IAEA provides support in building capacities of multidisciplinary teams of professionals, the provision of medical equipment and the promotion of communication and exchange of knowledge among the different stakeholders. In addition, the IAEA encourages the participation of nuclear medicine centers in international multi-center research studies. In this paper, we present some of the projects through which the IAEA has supported the LAC region, including regional technical cooperation projects and coordinated research projects related to cardiology within the current multimodality approach to cardiac imaging.


Assuntos
Técnicas de Imagem Cardíaca/tendências , Cardiologia/organização & administração , Doenças Cardiovasculares/diagnóstico por imagem , Medicina Nuclear/organização & administração , Cintilografia/tendências , Região do Caribe , Doença da Artéria Coronariana/diagnóstico por imagem , Países em Desenvolvimento , Humanos , Pesquisa Interdisciplinar , Agências Internacionais , Cooperação Internacional , América Latina , Imagem de Perfusão do Miocárdio , Medição de Risco
13.
Ann Oncol ; 30(5): 796-803, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30840064

RESUMO

BACKGROUND: Several studies show the importance of accurately quantifying not only KRAS and other low-abundant mutations because benefits of anti-EGFR therapies may depend on certain sensitivity thresholds. We assessed whether ultra-selection of patients using a high-sensitive digital PCR (dPCR) to determine KRAS, NRAS, BRAF and PIK3CA status can improve clinical outcomes of panitumumab plus FOLFIRI. PATIENTS AND METHODS: This was a single-arm phase II trial that analysed 38 KRAS, NRAS, BRAF and PIK3CA hotspots in tumour tissues of irinotecan-resistant metastatic colorectal cancer patients who received panitumumab plus FOLFIRI until disease progression or early withdrawal. Mutation profiles were identified by nanofluidic dPCR and correlated with clinical outcomes (ORR, overall response rate; PFS, progression-free survival; OS, overall survival) using cut-offs from 0% to 5%. A quantitative PCR (qPCR) analysis was also performed. RESULTS: Seventy-two evaluable patients were enrolled. RAS (KRAS/NRAS) mutations were detected in 23 (32%) patients and RAS/BRAF mutations in 25 (35%) by dPCR, while they were detected in 7 (10%) and 11 (15%) patients, respectively, by qPCR. PIK3CA mutations were not considered in the analyses as they were only detected in 2 (3%) patients by dPCR and in 1 (1%) patient by qPCR. The use of different dPCR cut-offs for RAS (KRAS/NRAS) and RAS/BRAF analyses translated into differential clinical outcomes. The highest ORR, PFS and OS in wild-type patients with their lowest values in patients with mutations were achieved with a 5% cut-off. We observed similar outcomes in RAS/BRAF wild-type and mutant patients defined by qPCR. CONCLUSIONS: High-sensitive dPCR accurately identified patients with KRAS, NRAS, BRAF and PIK3CA mutations. The optimal RAS/BRAF mutational cut-off for outcome prediction is 5%, which explains that the predictive performance of qPCR was not improved by dPCR. The biological and clinical implications of low-frequent mutated alleles warrant further investigations. CLINICALTRIALS.GOV NUMBER: NCT01704703. EUDRACT NUMBER: 2012-001955-38.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores Tumorais/genética , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Classe I de Fosfatidilinositol 3-Quinases/genética , Neoplasias Colorretais/patologia , Fluoruracila/administração & dosagem , GTP Fosfo-Hidrolases/genética , Genótipo , Humanos , Leucovorina/administração & dosagem , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Metástase Neoplásica , Panitumumabe/administração & dosagem , Estudos Prospectivos , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Taxa de Sobrevida
14.
Clin Transl Oncol ; 21(1): 46-54, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30565083

RESUMO

Colorectal cancer (CRC) is the second cause of cancer death in Spain, the objective of this guide published by the Spanish Society of Medical Oncology is to develop a consensus for the diagnosis and management of metastatic disease. The optimal treatment strategy for patients with metastatic CRC should be discussed in a multidisciplinary expert team to select the most appropriate treatment, and integrate systemic treatment and other options such as surgery and ablative techniques depending on the characteristics of the tumour, the patient and the location of the disease and metastases.


Assuntos
Neoplasias Colorretais/terapia , Neoplasias Hepáticas/terapia , Guias de Prática Clínica como Assunto/normas , Ensaios Clínicos como Assunto , Neoplasias Colorretais/patologia , Terapia Combinada , Gerenciamento Clínico , Humanos , Neoplasias Hepáticas/secundário , Prognóstico , Sociedades Médicas
15.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29778317

RESUMO

Across Latin American and Caribbean countries, cardiovascular disease and especially ischemic heart disease is currently the main cause of death both in men and in women. For most Latin American and Caribbean countries, public and community health efforts aim to define care strategies which are both clinically and cost effective and promote primary and secondary prevention, resulting in improved patient outcomes. The optimal approach to deal with acute events such as ST-elevation myocardial infarction (STEMI) is a matter of controversy; however, there is an expanding role for assessing residual ischemic burden in STEMI patients following primary percutaneous coronary intervention. Although randomized clinical trials have established the value of staged fractional flow reserve-guided revascularization, the use of noninvasive functional imaging modalities may play a similar role at a much lower cost. For LAC, available stress imaging techniques could be applied to define residual ischemia in the non-infarct related artery and to target revascularization in a staged procedure after primary percutaneous coronary intervention The use of nuclear cardiac imaging, supported by its relatively wide availability, moderate cost, and robust quantitative capabilities, may serve to guide effective care and to reduce subsequent cardiac events in patients with coronary artery disease. This noninvasive approach may avert potential safety issues with repeat and lengthy invasive procedures, and serve as a baseline for subsequent follow-up stress testing following the index STEMI event. This consensus document was devised from an expert panel meeting of the International Atomic Energy Agency, highlighting available evidence with a focus on the utility of stress myocardial perfusion imaging in post-STEMI patients. The document could serve as guidance to the prudent and appropriate use of nuclear imaging for targeting therapeutic management and avoiding unnecessary invasive procedures within Latin American and Caribbean countries, where resources could be scarce.


Assuntos
Técnicas de Imagem Cardíaca , Testes de Função Cardíaca , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Região do Caribe/epidemiologia , Tomada de Decisão Clínica , Doença das Coronárias/epidemiologia , Países em Desenvolvimento , Eletrocardiografia/métodos , Feminino , Humanos , América Latina/epidemiologia , Masculino , Estudos Multicêntricos como Assunto , Isquemia Miocárdica/diagnóstico por imagem , Intervenção Coronária Percutânea , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia
17.
Epidemiol Infect ; 145(15): 3143-3153, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28942750

RESUMO

Understanding infection dynamics in animal hosts is fundamental to managing spillover and emergence of zoonotic infections. Hendra virus is endemic in Australian pteropodid bat populations and can be lethal to horses and humans. However, we know little about the factors driving Hendra virus prevalence in resevoir bat populations, making spillover difficult to predict. We use Hendra virus prevalence data collected from 13 000 pooled bat urine samples across space and time to determine if pulses of prevalence are periodic and synchronized across sites. We also test whether site-specific precipitation and temperature affect the amplitude of the largest annual prevalence pulses. We found little evidence for a periodic signal in Hendra virus prevalence. Although the largest amplitude pulses tended to occur over winter, pulses could also occur in other seasons. We found that Hendra virus prevalence was weakly synchronized across sites over short distances, suggesting that prevalence is driven by local-scale effects. Finally, we found that drier conditions in previous seasons and the abundance of Pteropus alecto were positively correlated with the peak annual values of Hendra virus prevalence. Our results suggest that in addition to seasonal effects, bat density and local climatic conditions interact to drive Hendra virus infection dynamics.


Assuntos
Quirópteros/virologia , Vírus Hendra , Infecções por Henipavirus/veterinária , Animais , Austrália/epidemiologia , Clima , Reservatórios de Doenças/virologia , Vírus Hendra/fisiologia , Infecções por Henipavirus/epidemiologia , Prevalência , Estações do Ano , Análise Espaço-Temporal , Fatores de Tempo , Eliminação de Partículas Virais
18.
Ann Oncol ; 28(6): 1294-1301, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28368441

RESUMO

BACKGROUND: Circulating tumor DNA (ctDNA) is a potential source for tumor genome analysis. We explored the concordance between the mutational status of RAS in tumor tissue and ctDNA in metastatic colorectal cancer (mCRC) patients to establish eligibility for anti-epidermal growth factor receptor (EGFR) therapy. PATIENTS AND METHODS: A prospective-retrospective cohort study was carried out. Tumor tissue from 146 mCRC patients was tested for RAS status with standard of care (SoC) PCR techniques, and Digital PCR (BEAMing) was used both in plasma and tumor tissue. RESULTS: ctDNA BEAMing RAS testing showed 89.7% agreement with SoC (Kappa index 0.80; 95% CI 0.71 - 0.90) and BEAMing in tissue showed 90.9% agreement with SoC (Kappa index 0.83; 95% CI 0.74 - 0.92). Fifteen cases (10.3%) showed discordant tissue-plasma results. ctDNA analysis identified nine cases of low frequency RAS mutations that were not detected in tissue, possibly due to technical sensitivity or heterogeneity. In six cases, RAS mutations were not detected in plasma, potentially explained by low tumor burden or ctDNA shedding. Prediction of treatment benefit in patients receiving anti-EGFR plus irinotecan in second- or third-line was equivalent if tested with SoC PCR and ctDNA. Forty-eight percent of the patients showed mutant allele fractions in plasma below 1%. CONCLUSIONS: Plasma RAS determination showed high overall agreement and captured a mCRC population responsive to anti-EGFR therapy with the same predictive level as SoC tissue testing. The feasibility and practicality of ctDNA analysis may translate into an alternative tool for anti-EGFR treatment selection.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Genes ras , Mutação , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Humanos , Metástase Neoplásica
19.
Clin Transl Oncol ; 19(7): 884-890, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28150169

RESUMO

PURPOSE: Several angiogenic prognostic markers are under investigation because of their potential clinical utility, aiming to improve patient outcomes. We hypothesized that genetic variant in the VEGF pathway could be used as prognostic markers of survival in non-small cell lung cancer (NSCLC) patients undergoing pulmonary resection. METHODS: We evaluated the relationship between genetic variants in the VEGF pathway and relapse-free survival (RFS, main endpoint) and overall survival (OS, secondary endpoint) among 131 patients with stage I-III NSCLC treated with surgical resection from 2009 to 2013. Clinical, pathological and surgical data were prospectively collected. Twenty-five variants in sixteen relevant genes were selected and genotyped in tumor samples by real time PCR. The Kaplan-Meier method with the log-rank test and Cox's regression models were used for RFS and OS analyses. RESULTS: With a median follow-up of 36 (min = 2.8; max = 67.4) months, there were 31 (24%) relapses and 31 (24%) deaths. Overall, median RFS was not reached and median OS was 65 [95% confidence interval (CI) 56-75] months. The KRAS rs1137282 and PIK3C2A rs4356203 variants were significantly associated with RFS. For KRAS rs1137282, the 3-year RFS was 76% [95% CI 64-84%] in patients harboring an A/A genotype compared to 53% [95% CI 37-69%] in patients harboring an A/G or G/G genotype (p = 0.02). For PIK3C2A rs4356203, patients with an A/A or an A/G genotype had a 3-year RFS of 72% [95% CI 58-76%], whereas in patients with a G/G genotype was 49% [95% CI 28-70%] (p = 0.02). These associations remained statistically significant after adjusting for all the relevant clinical parameters in the multivariable analysis. CONCLUSION: Genetic variants in VEGF pathway may be associated with recurrence in stage I-III NSCLC. Specifically, the KRAS rs1137282 could be considered as a prognostic factor for recurrence in resectable NSCLC patients. Although PIK3C2A rs4356203 was associated with RFS, further analyses are necessary to confirm these data.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Recidiva Local de Neoplasia/genética , Neoplasias/tratamento farmacológico , Fosfatidilinositol 3-Quinases/genética , Polimorfismo Genético , Proteínas Proto-Oncogênicas p21(ras)/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/patologia , Carcinoma de Células Grandes/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Neoplasias/patologia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida
20.
J Evol Biol ; 29(12): 2480-2490, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27622965

RESUMO

Genotype-by-genotype (G×G) interactions are an essential requirement for the coevolution of hosts and parasites, but have only been documented in a small number of animal model systems. G×G effects arise from interactions between host and pathogen genotypes, such that some pathogen strains are more infectious in certain hosts and some hosts are more susceptible to certain pathogen strains. We tested for G×G interactions in the gypsy moth (Lymantria dispar) and its baculovirus. We infected 21 full-sib families of gypsy moths with each of 16 isolates of baculovirus and measured the between-isolate correlations of infection rate across host families for all pairwise combinations of isolates. Mean infectiousness varied among isolates and disease susceptibility varied among host families. Between-isolate correlations of infection rate were generally less than one, indicating nonadditive effects of host and pathogen type consistent with G×G interactions. Our results support the presence of G×G effects in the gypsy moth-baculovirus interaction and provide empirical evidence that correlations in infection rates between field-collected isolates are consistent with values that mathematical models have previously shown to increase the likelihood of pathogen polymorphism.


Assuntos
Baculoviridae/patogenicidade , Genótipo , Mariposas/virologia , Animais , Larva
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