Cetuximab plus platinum-based chemotherapy in head and neck Squamous Cell Carcinoma: a retrospective study in a single Comprehensive European Cancer Institution

Background: The use of cetuximab in combination with platinum (P) plus 5-fluorouracil (F) has previously been demonstrated to be effective in the treatment of metastatic squamous cell cancer of head and neck (SCCHN). We investigated the efficacy and outcome of this protocol as a first-line treatment for patients with recurrent or metastatic disease. We evaluated overall-survival (OS), progression-free-survival (PFS), overall response rate (ORR) and the treatment toxicity profile in a retrospective cohort. Patients and Methods: This study enrolled 121 patients with untreated recurrent or metastatic SCCHN. The patients received PF+ cetuximab every 3 weeks for a maximum of 6 cycles. Patients with stable disease who received PF+ cetuximab continued to receive cetuximab until disease progressed or unacceptable toxic effects were experienced, whichever occurred first. Results: The median patient age was 53 (37-78) years. The patient cohort was 86.8% male. The addition of cetuximab to PF in the recurrent or metastatic setting provided an OS of 11 months (Confidential Interval, CI, 95%, 8.684-13.316) and PFS of 8 months (CI 95%, 6.051-9.949). The disease control rate was 48.9%, and the ORR was 23.91%. The most common grade 3 or 4 adverse events in the PF+ cetuximab regimen were febrile neutropenia (5.7%), skin rash (3.8%) and mucosistis (3.8%). Conclusions: The results of this study suggest that cetuximab plus platinum-fluorouracil chemotherapy is a good option for systemic treatment in advanced SSCHN patients. This regimen has a well-tolerated toxicity profile.info:eu-repo/semantics/publishedVersio

Exame histológico de rotina na cirurgia endoscópica nasossinusal não complicada: necessário ou não?

Background: Functional Endoscopic sinus surgery (FESS) is an usual intervention, where most patients have Chronic Rhinosinusitis (CRS) which is not associated with complications. There is still no consensus on specific indications for histopathology examination. Aims: To evaluate the incidence of occult pathology in routine FESS and propose guidelines for histological analysis of specimens. Material and Methods: Retrospective analysis of 481 cases of patients undergoing uncomplicated FESS between January 2007 and January 2013. We analyzed several variables: age at surgery, diagnosis, laterality, tumor suspicion, final histological diagnosis. Results: Of the 410 cases (765 histologic results), aged 16-85 years, 61.7% male, the initial diagnosis was CRS with polyposis in 66.8% of cases. Bilateral pathology dominated (86.6%), and suspicion of tumor was found in surgery in 1.2% of cases, not confirmed histologically. The final histological diagnosis was CRS with polyposis in 71.2% (45.1% hypertrophic, 26.1% allergic), CRS without polyposis (25.1%), unspecified (2.9%) and fungal (0.7%). Conclusions: The histological review in routine uncomplicated FESS is questionable. Pathological examination is always indicated when there is: 1- intraoperative suspicion of tumor, 2 - unilateral pathology; 3 - need for complementary diagnostic (like screening of fungi / eosinophils).Introdução: A cirurgia endoscópica nasossinusal (CENS) é uma intervenção usual, onde a maioria dos doentes apresenta rinossinusite crónica (RSC) não complicada. Ainda não existe consenso sobre indicações específicas para estudo histopatológico das amostras. Objetivos: Avaliar a incidência de patologia oculta na CENS de rotina e sugerir linhas de orientação para o envio das amostras para estudo histopatológico. Material e Métodos: Análise retrospetiva de 481 processos de doentes submetidos a CENS por RSC não complicada entre Janeiro de 2007 e 2013. Foram analisadas diversas variáveis: idade na cirurgia, diagnóstico, lateralidade, suspeição tumoral, diagnóstico histológico final. Resultados: Dos 410 casos (765 histologias), com idades entre 16-85 anos, 61,7% sexo masculino, o diagnóstico de admissão foi RSC polipóide em 66,8% dos casos. A bilateralidade predominou (86,6%), com suspeição intra-operatoria em 1,2%, não confirmada histologicamente. O diagnóstico histológico final foi RSC polipóide em 71,2% (45,1% hipertrófica, 26,1% alérgica), RSC não polipóide (25,1%), inespecífica (2,9%) e fúngica (0,7%). Conclusões: A revisão histopatológica rotineira na CENS da RSC não complicada é questionável. O estudo anatomopatológico está indicado sempre em caso de: 1- suspeição intra-operatória de tumor; 2- patologia unilateral; 3- necessidade de diagnóstico complementar (como despiste de fungos /eosinófilos)

Heterologous expression of the human Copper Transporters hCTR1 and hCTR2 in yeast for endocytic trafficking analysis

SPB2016info:eu-repo/semantics/draf

Preparação tópica pré-nasofaringolaringoscopia: benefício real ou aparente?

Background: flexible nasendoscopy is routinely used in the Otolaryngology office. Often some degree of discomfort is reported by the patients examined. Topical agents, with different substances are therefore used in order to reduce the complaints. However, their benefit is debatable. Aims: to evaluate the necessity of topical preparation before flexible nasendoscopy, comparing its use with non-application. Material and Methods: prospective randomized study with patients undergoing flexible nasendoscopy in an office based procedure at CH VN Gaia / Espinho. They were randomly included in a group and after procedure completed a questionnaire, using a visual analogue scale. The operator was also evaluated in terms of image quality and ease of the technique. Results: 81 patients surveyed, with 0% dropouts. In all the variables studied, there were no significant statistically difference between the three groups, except in the variable flavor, with a significant difference when compared group 1with the remaining. Image quality and ease of the technique was not influenced by the group. Conclusions: The use of topical anesthetic or lubricant, does not confer significant benefit (or is costeffective feasible) to the non-application of preparation before flexible nasendoscopy, being sometimes associated with significant side effectsIntrodução: a nasofaringolaringoscopia é um meio complementar utilizado rotineiramente na especialidade de Otorrinolaringologia. Frequentemente é relatado desconforto nos doentes examinados. Agentes de aplicação tópica, com diferentes substâncias são utilizados, visando minorar as queixas. No entanto, é discutível o seu benefício. Objetivo: avaliar a eficácia e necessidade de preparação tópica antes da nasofaringolaringoscopia, comparando o seu uso com a não aplicação de preparação. Material e métodos: estudo prospetivo, randomizado, com doentes submetidos a nasofaringolaringoscopia na Consulta de Otorrinolaringologia do CH VNGaia/Espinho. Divididos em 3 grupos (com anestésico tópico, lubrificante ou sem preparação) com preenchimento de um questionário, recorrendo a escala visual analógica. O operador também avalia a qualidade de imagem e facilidade técnica. Resultados: inquiridos 81 doentes, com 0% de desistências. Das principais variáveis estudadas (dor e desconforto), não existiram diferenças estatisticamente significativas quando comparados os 3 grupos. Apenas na variável secundária sabor, houve diferença significativa quando comparado o grupo 1 com os restantes. A qualidade de imagem e a facilidade da técnica não foi influenciada pelo grupo em causa. Conclusões: o uso de anestésico ou lubrificante tópico não confere vantagem significativa (nem relação custo-benefício favorável), além de estar por vezes associado a efeitos laterais significativos

Study of the human copper transporters hCtr1 and hCtr2 using a yeast host

info:eu-repo/semantics/draf

Endocytosis of nutrient transporters in fungi: The ART of connecting signaling and trafficking

Plasma membrane transporters play pivotal roles in the import of nutrients, including sugars, amino acids, nucleobases, carboxylic acids, and metal ions, that surround fungal cells. The selective removal of these transporters by endocytosis is one of the most important regulatory mechanisms that ensures a rapid adaptation of cells to the changing environment (e.g., nutrient fluctuations or different stresses). At the heart of this mechanism lies a network of proteins that includes the arrestin‐related trafficking adaptors (ARTs) which link the ubiquitin ligase Rsp5 to nutrient transporters and endocytic factors. Transporter conformational changes, as well as dynamic interactions between its cytosolic termini/loops and with lipids of the plasma membrane, are also critical during the endocytic process. Here, we review the current knowledge and recent findings on the molecular mechanisms involved in nutrient transporter endocytosis, both in the budding yeast Saccharomyces cerevisiae and in some species of the filamentous fungus Aspergillus. We elaborate on the physiological importance of tightly regulated endocytosis for cellular fitness under dynamic conditions found in nature and highlight how further understanding and engineering of this process is essential to maximize titer, rate and yield (TRY)-values of engineered cell factories in industrial biotechnological processes.BT/Industrial Microbiolog

Treatment characteristics according to platinum used for CF+ cetuximab.

<p><b>Abbreviations</b>: PF, platinum (cisplatin or carboplatin) and 5-fluourouracil.</p>+<p>ORR refers to overall response rate and includes complete response and partial response.</p>++<p>Disease control rate includes complete response, partial response and stable disease.</p>*<p>Qui square test.</p>**<p>Median.</p>***<p>Mann-Whitney U Test.</p

Grade 3 and/or grade 4 adverse effects observed according to CTCAE version 4.0.

<p><b>Abbreviations</b>: CTCAE, Common Terminology Criteria for Adverse Events. 5FU, 5-fluourouracil.</p

Show PFS of all patient treated with platinum +5-FU +cetuximab (A); and stratified by platinum (B): carboplatin +5-FU+cetuximab versus cisplatin +5-FU+cetuximab.

<p>Analysis was performed using log-rank test. Abbreviations: PFS stands for progression-free-survival; C stands for platinum (carboplatin or cisplatin); 5-FU stands for 5-fluourouracil.</p

Characteristics of patients treated with platinum in combination with 5-FU plus cetuximab.

<p><b>Abbreviations</b>: ECOG PS, eastern cooperative oncology group performance status; 5-FU, 5-fluourouracil.</p