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Lorenzi A.T.,Barretos Cancer Hospital | Fregnani J.H.T.,Barretos Cancer Hospital | Possati-Resende J.C.,Barretos Cancer Hospital | Antoniazzi M.,Barretos Cancer Hospital | And 7 more authors.
Cancer Cytopathology | Year: 2016

BACKGROUND: Human papillomavirus (HPV) DNA testing can be crucial for women who have limited access to traditional screening. The current study compared the results obtained through HPV DNA testing with those obtained through cytology-based screening. METHODS: A total of 3068 women aged 18 to 85 years were enrolled in an opportunistic cervical cancer screening program developed by the Barretos Cancer Hospital and performed by a team of health professionals working within a mobile unit from March to December 2012, followed by statistical analyses. For each patient, 2 different cervical samples were collected and preserved in a careHPV assay and SurePath medium, respectively. RESULTS: High-risk HPV (hr-HPV) DNA was detected in 10.0% of women, with the majority (86.7%) demonstrating no abnormal Papanicolaou test results. The following cytological samples were found to be hr-HPV positive: 8.2% of the normal samples; 39.4% of the samples with atypical squamous/glandular cells of undetermined significance; 38.5% of the samples with atypical squamous/glandular cells of undetermined significance, cannot exclude high-grade lesion; 55.3% of the samples with low-grade squamous intraepithelial lesions; and 100% of the samples with high-grade squamous intraepithelial lesions. Colposcopy examinations were performed among 33.4% of the women with positive results on at least 1 of the tests (HPV DNA positive and/or cytology with atypical squamous/glandular cells of undetermined significance, cannot exclude high-grade lesion or high-grade squamous intraepithelial lesions), and 59.5% of these women underwent biopsies. Among these samples, 18.2% were confirmed as cervical intraepithelial neoplasia. CONCLUSIONS: The careHPV test was demonstrated to be a feasible alternative to primary screening in low-resource settings accessed through the use of mobile units. Cancer Cytopathol 2016;124:581-8. © 2016 American Cancer Society. © 2016 American Cancer Society

Martinho O.,University of Minho | Martinho O.,Life and Health science Research Institute 3Bs PT Government Associate Laboratory | Granja S.,University of Minho | Granja S.,Life and Health science Research Institute 3Bs PT Government Associate Laboratory | And 12 more authors.
PLoS ONE | Year: 2012

Malignant gliomas are highly infiltrative and invasive tumors, which precludes the few treatment options available. Therefore, there is an urgent need to elucidate the molecular mechanisms underlying gliomas aggressive phenotype and poor prognosis. The Raf Kinase Inhibitory protein (RKIP), besides regulating important intracellular signaling cascades, was described to be associated with progression, metastasis and prognosis in several human neoplasms. Its role in the prognosis and tumourigenesis of gliomas remains unclear. In the present study, we found that RKIP protein is absent in a low frequency (10%, 20/193) of glioma tumors. Nevertheless, the absence of RKIP expression was an independent prognostic marker in glioma. Additionally, by in vitro downregulation of RKIP, we found that RKIP inhibition induces a higher viability and migration of the cells, having no effect on cellular proliferation and angiogenesis, as assessed by in vivo CAM assay. In conclusion, this is the largest series studied so far evaluating the expression levels of this important cancer suppressor protein in glioma tumors. Our results suggest that in a subset of tumors, the absence of RKIP associates with highly malignant behavior and poor survival of patients, which may be a useful biomarker for tailored treatment of glioma patients. © 2012 Martinho et al.

van der Wiel S.E.,Erasmus University Rotterdam | Kuttner Magalhaes R.,Abel Salazar Biomedical Sciences Institute | Rocha Goncalves C.R.,University of Minho | Rocha Goncalves C.R.,Life and Health science Research Institute 3Bs PT Government Associate Laboratory | And 4 more authors.
Best Practice and Research: Clinical Gastroenterology | Year: 2016

Simulator-based gastrointestinal endoscopy training has gained acceptance over the last decades and has been extensively studied. Several types of simulators have been validated and it has been demonstrated that the use of simulators in the early training setting accelerates the learning curve in acquiring basic skills. Current GI endoscopy simulators lack the degree of realism that would be necessary to provide training to achieve full competency or to be applicable in certification. Virtual Reality and mechanical simulators are commonly used in basic flexible endoscopy training, whereas ex vivo and in vivo models are used in training the most advanced endoscopic procedures. Validated models for the training of more routine therapeutic interventions like polypectomy, EMR, stenting and haemostasis are lacking or scarce and developments in these areas should be encouraged. © 2016 Elsevier Ltd.

Nogueira-Silva C.,University of Minho | Nogueira-Silva C.,Life and Health science Research Institute 3Bs PT Government Associate Laboratory | Nogueira-Silva C.,Hospital Of Braga | Piairo P.,University of Minho | And 11 more authors.
PLoS ONE | Year: 2013

The glycoprotein 130 (gp130) dependent family of cytokines comprises interleukin-6 (IL-6), IL-11, leukemia inhibitory factor (LIF), cardiotrophin-like cytokine (CLC), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1) and oncostatin M (OSM). These cytokines share the membrane gp130 as a common signal transducer. Recently, it was demonstrated that IL-6 promotes, whereas LIF inhibits fetal lung branching. Thus, in this study, the effects on fetal lung morphogenesis of the other classical members of the gp130-type cytokines (IL-11, CLC, CNTF, CT-1 and OSM) were investigated. We also provide the first description of these cytokines and their common gp130 receptor protein expression patterns during rat lung development. Fetal rat lung explants were cultured in vitro with increasing concentrations of IL-11, CLC, CNTF, CT-1 and OSM. Treated lung explants were morphometrically analyzed and assessed for MAPK, PI3K/AKT and STAT3 signaling modifications. IL-11, which similarly to IL-6 acts through a gp130 homodimer receptor, significantly stimulated lung growth via p38 phosphorylation. On the other hand, CLC, CNTF, CT-1 and OSM, whose receptors are gp130 heterodimers, inhibited lung growth acting in different signal-transducing pathways. Thus, the present study demonstrated that although cytokines of the gp130 family share a common signal transducer, there are specific biological activities for each cytokine on lung development. Indeed, cytokine signaling through gp130 homodimers stimulate, whereas cytokine signaling through gp130 heterodimers inhibit lung branching. © 2013 Nogueira-Silva et al.

Cunha C.,University of Perugia | Giovannini G.,University of Perugia | Pierini A.,University of Perugia | Bell A.S.,University of Perugia | And 11 more authors.
PLoS ONE | Year: 2011

Invasive aspergillosis (IA) is a major threat to the successful outcome of hematopoietic stem cell transplantation (HSCT), although individual risk varies considerably. Recent evidence has established a pivotal role for a danger sensing mechanism implicating the S100B/receptor for advanced glycation end products (RAGE) axis in antifungal immunity. The association of selected genetic variants in the S100B/RAGE axis with susceptibility to IA was investigated in 223 consecutive patients undergoing HSCT. Furthermore, studies addressing the functional consequences of these variants were performed. Susceptibility to IA was significantly associated with two distinct polymorphisms in RAGE (-374T/A) and S100B (+427C/T) genes, the relative contribution of each depended on their presence in both transplantation counterparts [patient SNP RAGE, adjusted hazard ratio (HR), 1.97; P = 0.042 and donor SNP RAGE, HR, 2.03; P = 0.047] or in donors (SNP S100B, HR, 3.15; P = 7.8e- 4) only, respectively. Functional assays demonstrated a gain-of-function phenotype of both variants, as shown by the enhanced expression of inflammatory cytokines in RAGE polymorphic cells and increased S100B secretion in vitro and in vivo in the presence of the S100B polymorphism. These findings point to a relevant role of the danger sensing signaling in human antifungal immunity and highlight a possible contribution of a genetically-determined hyperfunction of the S100B/RAGE axis to susceptibility to IA in the HSCT setting. © 2011 Cunha et al.

Silva A.,University of Minho | Silva A.,Life and Health science Research Institute 3Bs PT Government Associate Laboratory | Sampaio-Marques B.,University of Minho | Sampaio-Marques B.,Life and Health science Research Institute 3Bs PT Government Associate Laboratory | And 9 more authors.
PLoS ONE | Year: 2013

Acetic acid-induced apoptosis in yeast is accompanied by an impairment of the general protein synthesis machinery, yet paradoxically also by the up-regulation of the two isoforms of the heat shock protein 90 (HSP90) chaperone family, Hsc82p and Hsp82p. Herein, we show that impairment of cap-dependent translation initiation induced by acetic acid is caused by the phosphorylation and inactivation of eIF2α by Gcn2p kinase. A microarray analysis of polysome-associated mRNAs engaged in translation in acetic acid challenged cells further revealed that HSP90 mRNAs are over-represented in this polysome fraction suggesting preferential translation of HSP90 upon acetic acid treatment. The relevance of HSP90 isoform translation during programmed cell death (PCD) was unveiled using genetic and pharmacological abrogation of HSP90, which suggests opposing roles for HSP90 isoforms in cell survival and death. Hsc82p appears to promote survival and its deletion leads to necrotic cell death, while Hsp82p is a pro-death molecule involved in acetic acid-induced apoptosis. Therefore, HSP90 isoforms have distinct roles in the control of cell fate during PCD and their selective translation regulates cellular response to acetic acid stress. © 2013 Silva et al.

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