37 results on '"Afonso LP"'
Search Results
2. Endoscopic Submucosal Dissection: Recurrence Among R0 Resections… How to Explain?
- Author
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Rodríguez-Carrasco, M, additional, Libânio, D, additional, Pimentel-Nunes, P, additional, Afonso, LP, additional, Monterio, P, additional, and Dinis-Ribeiro, M, additional
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- 2021
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3. RELIABILITY AND ACCURACY OF BLUE LIGHT IMAGING FOR STAGING OF INTESTINAL METAPLASIA IN STOMACH (BLIMPS)
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Castro, R, additional, Libânio, D, additional, Santos, C, additional, Afonso, LP, additional, Pimentel-Nunes, P, additional, and Dinis-Ribeiro, M, additional
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- 2019
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4. Advanced Injection of Botulinum Toxin in the Nasal Muscles: A Novel Dynamic Change in Facial Expression.
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Ramos HHA, Amaral V, de Oliveira Afonso LP, Campagnaro JCM, Gazzinelli HCG, Muzy G, and de Almeida ART
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- Humans, Retrospective Studies, Female, Adult, Middle Aged, Male, Injections, Intramuscular, Treatment Outcome, Nose, Cohort Studies, Esthetics, Neuromuscular Agents administration & dosage, Facial Muscles drug effects, Botulinum Toxins, Type A administration & dosage, Facial Expression
- Abstract
Background: Among the nasal muscles, the levator labii superior alaeque nasi (LLSAN) acts as a transitional muscle that conjugates with other nasal and perinasal muscles. Thus, when treating the nasal region with Botulinum toxin (BTX), it is important to understand local nasal muscular dynamics and how they can influence the muscular dynamics of the entire face., Methods: This is a retrospective analysis of cases treated by an injection pattern encompassing the face, including nasal muscles. Photographs were taken at rest and during motion (frontal and oblique views), before and after treatment., Results: A total of 227 patients have been treated in the last 18 months with the following results: eyebrow tail lifting, softness of crow's feet, improvement of the drooping of the tip of the nose, and shortening of the lip philtrum when smiling. We present cases illustrating the use of this approach., Conclusions: Treating the facial muscles globally (including the frontal, corrugators, procerus, orbicularis oculi, platysma, DAO, and nasal muscles) can improve the smile and facial expressions. This is believed to occur because the elevated portion of the upper lip muscle becomes stronger as the nasal part of the LLSAN is paralyzed., Level of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)
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- 2024
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5. Stool Glycoproteomics Signatures of Pre-Cancerous Lesions and Colorectal Cancer.
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Soares J, Eiras M, Ferreira D, Santos DAR, Relvas-Santos M, Santos B, Gonçalves M, Ferreira E, Vieira R, Afonso LP, Santos LL, Dinis-Ribeiro M, Lima L, and Ferreira JA
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- Humans, Hyperplasia, Carcinogenesis, Antigens, Viral, Tumor, Colorectal Neoplasms diagnosis, Precancerous Conditions
- Abstract
Colorectal cancer (CRC) screening relies primarily on stool analysis to identify occult blood. However, its sensitivity for detecting precancerous lesions is limited, requiring the development of new tools to improve CRC screening. Carcinogenesis involves significant alterations in mucosal epithelium glycocalyx that decisively contribute to disease progression. Building on this knowledge, we examined patient series comprehending premalignant lesions, colorectal tumors, and healthy controls for the T-antigen-a short-chain O -glycosylation of proteins considered a surrogate marker of malignancy in multiple solid cancers. We found the T-antigen in the secretions of dysplastic lesions as well as in cancer. In CRC, T-antigen expression was associated with the presence of distant metastases. In parallel, we analyzed a broad number of stools from individuals who underwent colonoscopy, which showed high T expressions in high-grade dysplasia and carcinomas. Employing mass spectrometry-based lectin-affinity enrichment, we identified a total of 262 proteins, 67% of which potentially exhibited altered glycosylation patterns associated with cancer and advanced pre-cancerous lesions. Also, we found that the stool (glyco)proteome of pre-cancerous lesions is enriched for protein species involved in key biological processes linked to humoral and innate immune responses. This study offers a thorough analysis of the stool glycoproteome, laying the groundwork for harnessing glycosylation alterations to improve non-invasive cancer detection.
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- 2024
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6. Aberrantly Glycosylated GLUT1 as a Poor Prognosis Marker in Aggressive Bladder Cancer.
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Ferreira E, Ferreira D, Relvas-Santos M, Freitas R, Soares J, Azevedo R, Afonso LP, Lima L, Santos B, Gonçalves M, Silva AMN, Santos LL, Peixoto A, and Ferreira JA
- Subjects
- Humans, Glycosylation, Glucose Transporter Type 1 metabolism, Urinary Bladder pathology, Tandem Mass Spectrometry, Urinary Bladder Neoplasms metabolism
- Abstract
Muscle-invasive bladder cancer (MIBC) remains a pressing health concern due to conventional treatment failure and significant molecular heterogeneity, hampering the development of novel targeted therapeutics. In our quest for novel targetable markers, recent glycoproteomics and bioinformatics data have pinpointed (glucose transporter 1) GLUT1 as a potential biomarker due to its increased expression in tumours compared to healthy tissues. This study explores this hypothesis in more detail, with emphasis on GLUT1 glycosylation patterns and cancer specificity. Immunohistochemistry analysis across a diverse set of human bladder tumours representing all disease stages revealed increasing GLUT1 expression with lesion severity, extending to metastasis, while remaining undetectable in healthy urothelium. In line with this, GLUT1 emerged as a marker of reduced overall survival. Revisiting nanoLC-EThcD-MS/MS data targeting immature O -glycosylation on muscle-invasive tumours identified GLUT1 as a carrier of short glycosylation associated with invasive disease. Precise glycosite mapping uncovered significant heterogeneity between patient samples, but also common glycopatterns that could provide the molecular basis for targeted solutions. Immature O -glycosylation conferred cancer specificity to GLUT1, laying the molecular groundwork for enhanced targeted therapeutics in bladder cancer. Future studies should focus on a comprehensive mapping of GLUT1 glycosites for highly specific cancer-targeted therapy development for bladder cancer.
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- 2024
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7. Unexpected pancreatic mixed neuroendocrine-nonneuroendocrine neoplasms (MiNEN)-reflection on a case report.
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Baía CAQ, Sousa A, Sousa F, Santos P, Varelas AI, Afonso LP, Monteiro J, Fernandes JM, Santos LL, and Abreu de Sousa J
- Abstract
The authors present a case involving a 51-year-old male who was diagnosed with a 4-cm mass in the body of the pancreas, initially suspected to be a ductal adenocarcinoma due to an elevated Ca 19.9 during routine analysis. Subsequent imaging studies confirmed a resectable disease without suspicious lymph nodes or distant metastasis, leading to the proposal of surgery. The patient underwent a laparoscopic distal splenopancreatectomy, which was uneventful. The histopathological examination revealed a 3.7-cm pancreatic mixed neuroendocrine neoplasia (MiNEN) with a predominant high-grade ductal adenocarcinoma component and a concurrent high-grade neuroendocrine carcinoma, with negative margins. Two lymph node metastases were identified, each representing metastasis of one of the components. The tumor was classified as pT2N1M0. Currently, the patient is undergoing chemotherapy with FOLFIRINOX. This case prompts reflection on the optimal treatment strategy for pancreatic MiNEN and raises the question of how the preoperative diagnosis could influence the patient's outcome., Competing Interests: None declared., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)
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- 2024
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8. Metachronous lesions after gastric endoscopic submucosal dissection: first assessment of the FAMISH prediction score.
- Author
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Rei A, Ortigão R, Pais M, Afonso LP, Pimentel-Nunes P, Dinis-Ribeiro M, and Libânio D
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- Aged, Female, Humans, Male, Cohort Studies, Gastric Mucosa surgery, Gastric Mucosa pathology, Gastroscopy adverse effects, Incidence, Retrospective Studies, Endoscopic Mucosal Resection adverse effects, Helicobacter Infections diagnosis, Helicobacter pylori, Stomach Neoplasms surgery, Stomach Neoplasms epidemiology
- Abstract
Background: Surveillance after gastric endoscopic submucosal dissection (ESD) is recommended for all patients owing to the persistent risk of metachronous gastric lesions (MGLs). We developed and validated a prediction score to estimate MGL risk after ESD for early neoplastic gastric lesions, to define an individualized and cost-saving approach., Methods: Clinical predictors and a risk score were derived from meta-analysis data. A retrospective, single-center, cohort study including patients with ≥ 3 years of standardized surveillance after ESD was conducted for score validation. Predictive accuracy of the score by the area under the receiver operating characteristic curve (AUC) was assessed and cumulative probabilities of MGL were estimated., Results: The risk score (0-9 points) included six clinical predictors (scored 0-3): positive family history of gastric cancer, older age, male sex, corpus intestinal metaplasia, synchronous gastric lesions, and persistent Helicobacter pylori infection (FAMISH). The study population included 263 patients. The MGL rate was 16 %. The score diagnostic accuracy for predicting MGL at 3 years' follow-up, measured by the AUC, was 0.704 (95 %CI 0.603-0.806). At 3 years and a cutoff < 2, the score achieved maximal sensitivity and negative predictive value; 15 % of patients could be assigned to a low-risk group, in which the progression to MGL was significantly lower than for the high-risk group ( P = 0.04)., Conclusion: The FAMISH score might be a useful tool to accurately identify patients with low-to-intermediate risk for MGL at 3 years of follow-up who could have surveillance intervals extended to reduce the burden of care., Competing Interests: M. Dinis-Ribeiro has been a consultant for Roche (2022) and Medtronic (2021). A. Rei, R. Ortigão, M. Pais, L.P. Afonso, P. Pimentel-Nunes, and D. Libânio, declare that they have no conflict of interest., (Thieme. All rights reserved.)
- Published
- 2023
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9. Predictors of Outcomes in Gastric Neuroendocrine Tumors: A Retrospective Cohort.
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Ortigão R, Afonso LP, Pimentel-Nunes P, Dinis-Ribeiro M, and Libânio D
- Abstract
Introduction/aim: Gastric neuroendocrine tumors (GNETs) frequently have an indolent clinical course, despite their metastatic potential. The aim of the study was to identify prognostic factors associated with overall survival and risk of metastases and to evaluate the impact of serial measurements of chromogranin A (CgA)., Methods: The authors performed a retrospective cohort study including consecutive patients with GNET diagnosed between 2010 and 2019, with a minimum follow-up of 1 year. Univariate and multivariate analyses were performed., Results: We included 132 patients with GNET (type I, 113 patients; type II, 1 patient; type III, 14 patients; type IV, 2 patients; not classifiable, 2 patients), with 61% being female and a mean age at diagnosis of 66 years. During the follow-up period (median 66 months), 3 (2.3%) patients died due to metastatic disease (1 patient with type III and 2 patients with type IV). Male gender ( p = 0.030), type III/IV ( p < 0.001), Ki-67 index >20% ( p < 0.001), grade 2/3 ( p < 0.001), invasion beyond the submucosa ( p < 0.001), and presence of metastases ( p < 0.001) were identified as risk factors for mortality in the univariate analysis. Metastasis developed in 7 patients (5.3%). Multivariable analysis revealed that Ki-67 >20% ( p = 0.016) was an independent risk factor for metastasis. Overall, CgA showed a sensitivity of 20% for detection of recurrence and a specificity of 79% (sensitivity of 8% and specificity of 71% in type I GNETs)., Conclusion: Identification of risk factors for the presence of metastases and for mortality in these groups of patients can help in individualizing the therapeutic strategy. CgA seems to be a weak marker for monitoring patients with GNET., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 The Author(s). Published by S. Karger AG, Basel.)
- Published
- 2023
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10. Syndecan-4 is a maestro of gastric cancer cell invasion and communication that underscores poor survival.
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Poças J, Marques C, Gomes C, Otake AH, Pinto F, Ferreira M, Silva T, Faria-Ramos I, Matos R, Ribeiro AR, Senra E, Cavadas B, Batista S, Maia J, Macedo JA, Lima L, Afonso LP, Ferreira JA, Santos LL, Polónia A, Osório H, Belting M, Reis CA, Costa-Silva B, and Magalhães A
- Subjects
- Humans, Heparitin Sulfate metabolism, Neoplasm Invasiveness, Stomach Neoplasms genetics, Syndecan-4 genetics, Syndecan-4 metabolism
- Abstract
Gastric cancer is a dominating cause of cancer-associated mortality with limited therapeutic options. Here, we show that syndecan-4 (SDC4), a transmembrane proteoglycan, is highly expressed in intestinal subtype gastric tumors and that this signature associates with patient poor survival. Further, we mechanistically demonstrate that SDC4 is a master regulator of gastric cancer cell motility and invasion. We also find that SDC4 decorated with heparan sulfate is efficiently sorted in extracellular vesicles (EVs). Interestingly, SDC4 in EVs regulates gastric cancer cell-derived EV organ distribution, uptake, and functional effects in recipient cells. Specifically, we show that SDC4 knockout disrupts the tropism of EVs for the common gastric cancer metastatic sites. Our findings set the basis for the molecular implications of SDC4 expression in gastric cancer cells and provide broader perspectives on the development of therapeutic strategies targeting the glycan-EV axis to limit tumor progression.
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- 2023
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11. Not a neuroendocrine tumor: A case of hepatocellular carcinoma in ectopic liver tissue in the pancreas.
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Correia AM, Ribeiro C, Videira F, Gigliano D, Cunha AL, Afonso LP, Peyroteo M, Canotilho R, Baía C, Sousa F, and de Sousa JA
- Abstract
Hepatocellular carcinoma (HCC) accounts for most of the hepatic neoplasms and can also occur in ectopic liver tissue. We present a case of a 55-year-old male complaining of weight loss. The imaging studies reported a 2.9 cm nodule in the pancreatic body, with a neuroendocrine tumor diagnosis by cytology. A corpo-caudal pancreatectomy was performed. Pathology showed a well-differentiated HCC developed in ectopic liver tissue with free margins and no lymph node metastases. HCC presenting in ectopic liver tissue is rare. In this case, the preoperative study did not establish the diagnosis, warranting the need for suspicion of this neoplasm.
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- 2023
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12. Endoscopic Resection of Gastrointestinal Neuroendocrine Tumors: Long-Term Outcomes and Comparison of Endoscopic Techniques.
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Pimentel-Nunes P, Ortigão R, Afonso LP, Bastos RP, Libânio D, and Dinis-Ribeiro M
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Introduction: Gastrointestinal neuroendocrine tumors (GI-NETs) are being more frequently diagnosed and treated by endoscopic resection (ER) techniques. However, comparison studies of the different ER techniques or long-term outcomes are rarely reported., Methods: This was a single-center retrospective study analyzing short and long-term outcomes after ER of gastric, duodenum, and rectal GI-NETs. Comparison between standard EMR (sEMR), EMR with a cap (EMRc), and endoscopic submucosal dissection (ESD) was made., Results: Fifty-three patients with GI-NET (25 gastric, 15 duodenal, and 13 rectal; sEMR = 21; EMRc = 19; ESD = 13) were included in the analysis. Median tumor size was 11 mm (range 4-20), significantly larger in the ESD and EMRc groups compared to the sEMR group ( p < 0.05). Complete ER was possible in all cases with 68% histological complete resection (no difference between the groups). Complication rate was significantly higher in the EMRc group (EMRc 32%, ESD 8%, and EMRs 0%, p = 0.01). Local recurrence occurred in only one patient, and systemic recurrence in 6%, with size ≥ 12 mm being a risk factor for systemic recurrence (p = 0.05). Specific disease-free survival after ER was 98%., Conclusion: ER is a safe and highly effective treatment particularly for less than 12 mm luminal GI-NETs. EMRc is associated with a high complication rate and should be avoided. sEMR is an easy and safe technique that is associated with long-term curability, and it is probably the best therapeutic option for most luminal GI-NETs. ESD appears to be the best option for lesions that cannot be resected en bloc with sEMR. Multicenter, prospective randomized trials should confirm these results., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel.)
- Published
- 2022
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13. Complete endoscopic removal of a large appendiceal orifice polyp.
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Carvão J, Libânio D, Rodríguez-Carrasco M, Souto Moura M, Afonso LP, and Dinis-Ribeiro M
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- Endoscopy, Humans, Appendix diagnostic imaging, Appendix surgery
- Abstract
Competing Interests: The authors declare that they have no conflict of interest.
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- 2022
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14. The Extremely Rare Hypopharyngeal Fetal Rhabdomyoma in an Adult.
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Baraças C, Farinha M, Afonso LP, and Bacelar MT
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Extracardiac rhabdomyomas are rare benign tumors showing skeletal muscle differentiation. They can be divided into adult, fetal, and genital subtypes. Fetal rhabdomyomas are rarer than the adult subtype and although usually diagnosed at birth, the diagnosis is based on histology rather than patient age. We present a rare case of a 25-year-old man with a cellular fetal (juvenile) rhabdomyoma, found in the postcricoid region of the hypopharynx., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Baraças et al.)
- Published
- 2021
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15. Repeated Administration of Clinically Relevant Doses of the Prescription Opioids Tramadol and Tapentadol Causes Lung, Cardiac, and Brain Toxicity in Wistar Rats.
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Barbosa J, Faria J, Garcez F, Leal S, Afonso LP, Nascimento AV, Moreira R, Pereira FC, Queirós O, Carvalho F, and Dinis-Oliveira RJ
- Abstract
Tramadol and tapentadol, two structurally related synthetic opioid analgesics, are widely prescribed due to the enhanced therapeutic profiles resulting from the synergistic combination between μ-opioid receptor (MOR) activation and monoamine reuptake inhibition. However, the number of adverse reactions has been growing along with their increasing use and misuse. The potential toxicological mechanisms for these drugs are not completely understood, especially for tapentadol, owing to its shorter market history. Therefore, in the present study, we aimed to comparatively assess the putative lung, cardiac, and brain cortex toxicological damage elicited by the repeated exposure to therapeutic doses of both prescription opioids. To this purpose, male Wistar rats were intraperitoneally injected with single daily doses of 10, 25, and 50 mg/kg tramadol or tapentadol, corresponding to a standard analgesic dose, an intermediate dose, and the maximum recommended daily dose, respectively, for 14 consecutive days. Such treatment was found to lead mainly to lipid peroxidation and inflammation in lung and brain cortex tissues, as shown through augmented thiobarbituric acid reactive substances (TBARS), as well as to increased serum inflammation biomarkers, such as C reactive protein (CRP) and tumor necrosis factor-α (TNF-α). Cardiomyocyte integrity was also shown to be affected, since both opioids incremented serum lactate dehydrogenase (LDH) and α-hydroxybutyrate dehydrogenase (α-HBDH) activities, while tapentadol was associated with increased serum creatine kinase muscle brain (CK-MB) isoform activity. In turn, the analysis of metabolic parameters in brain cortex tissue revealed increased lactate concentration upon exposure to both drugs, as well as augmented LDH and creatine kinase (CK) activities following tapentadol treatment. In addition, pneumo- and cardiotoxicity biomarkers were quantified at the gene level, while neurotoxicity biomarkers were quantified both at the gene and protein levels; changes in their expression correlate with the oxidative stress, inflammatory, metabolic, and histopathological changes that were detected. Hematoxylin and eosin (H & E) staining revealed several histopathological alterations, including alveolar collapse and destruction in lung sections, inflammatory infiltrates, altered cardiomyocytes and loss of striation in heart sections, degenerated neurons, and accumulation of glial and microglial cells in brain cortex sections. In turn, Masson's trichrome staining confirmed fibrous tissue deposition in cardiac tissue. Taken as a whole, these results show that the repeated administration of both prescription opioids extends the dose range for which toxicological injury is observed to lower therapeutic doses. They also reinforce previous assumptions that tramadol and tapentadol are not devoid of toxicological risk even at clinical doses.
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- 2021
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16. Repeated Administration of Clinical Doses of Tramadol and Tapentadol Causes Hepato- and Nephrotoxic Effects in Wistar Rats.
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Barbosa J, Faria J, Garcez F, Leal S, Afonso LP, Nascimento AV, Moreira R, Queirós O, Carvalho F, and Dinis-Oliveira RJ
- Abstract
Tramadol and tapentadol are fully synthetic and extensively used analgesic opioids, presenting enhanced therapeutic and safety profiles as compared with their peers. However, reports of adverse reactions, intoxications and fatalities have been increasing. Information regarding the molecular, biochemical, and histological alterations underlying their toxicological potential is missing, particularly for tapentadol, owing to its more recent market authorization. Considering the paramount importance of liver and kidney for the metabolism and excretion of both opioids, these organs are especially susceptible to toxicological damage. In the present study, we aimed to characterize the putative hepatic and renal deleterious effects of repeated exposure to therapeutic doses of tramadol and tapentadol, using an in vivo animal model. Male Wistar rats were randomly divided into six experimental groups, composed of six animals each, which received daily single intraperitoneal injections of 10, 25 or 50 mg/kg tramadol or tapentadol (a low, standard analgesic dose, an intermediate dose and the maximum recommended daily dose, respectively). An additional control group was injected with normal saline. Following 14 consecutive days of administration, serum, urine and liver and kidney tissue samples were processed for biochemical, metabolic and histological analysis. Repeated administration of therapeutic doses of both opioids led to: (i) increased lipid and protein oxidation in liver and kidney, as well as to decreased total liver antioxidant capacity; (ii) decreased serum albumin, urea, butyrylcholinesterase and complement C3 and C4 levels, denoting liver synthesis impairment; (iii) elevated serum activity of liver enzymes, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and γ-glutamyl transpeptidase, as well as lipid profile alterations, also reflecting hepatobiliary commitment; (iv) derangement of iron metabolism, as shown through increases in serum iron, ferritin, haptoglobin and heme oxygenase-1 levels. In turn, elevated serum cystatin C, decreased urine creatinine output and increased urine microalbumin levels were detected upon exposure to tapentadol only, while increased serum amylase and urine N -acetyl-β-D-glucosaminidase activities were observed for both opioids. Collectively, these results are compatible with kidney injury. Changes were also found in the expression levels of liver- and kidney-specific toxicity biomarker genes, upon exposure to tramadol and tapentadol, correlating well with alterations in lipid profile, iron metabolism and glomerular and tubular function. Histopathological analysis evidenced sinusoidal dilatation, microsteatosis, mononuclear cell infiltrates, glomerular and tubular disorganization, and increased Bowman's spaces. Although some findings are more pronounced upon tapentadol exposure, our study shows that, when compared with acute exposure, prolonged administration of both opioids smooths the differences between their toxicological effects, and that these occur at lower doses within the therapeutic range.
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- 2020
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17. Esophageal pseudoperforation during band mucosectomy of Barrett's esophagus: not all that glitters is gold (with video).
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Pita I, Gigliano D, Afonso LP, Libânio D, and Dinis-Ribeiro M
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- Esophageal Neoplasms, Esophagoscopy, Humans, Barrett Esophagus surgery
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- 2020
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18. Nucleolin-Sle A Glycoforms as E-Selectin Ligands and Potentially Targetable Biomarkers at the Cell Surface of Gastric Cancer Cells.
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Fernandes E, Freitas R, Ferreira D, Soares J, Azevedo R, Gaiteiro C, Peixoto A, Oliveira S, Cotton S, Relvas-Santos M, Afonso LP, Palmeira C, Oliveira MJ, Ferreira R, Silva AMN, Lara Santos L, and Ferreira JA
- Abstract
Background: Gastric cancer (GC) is a major health burden worldwide, with half of patients developing metastases within 5 years after treatment, urging novel biomarkers for diagnosis and efficient therapeutic targeting. Sialyl-Lewis A (SLeA), a terminal glycoepitope of glycoproteins and glycolipids, offers tremendous potential towards this objective. It is rarely expressed in healthy tissues and blood cells, while it is present in highly metastatic cell lines and metastases. SLeA is also involved in E-selectin mediated metastasis, making it an ideal target to control disease dissemination., Methods and Results: To improve cancer specificity, we have explored the SLeA-glycoproteome of six GC cell models, with emphasis on glycoproteins showing affinity for E-selectin. A novel bioinformatics-assisted algorithm identified nucleolin (NCL), a nuclear protein, as a potential targetable biomarker potentially involved in metastasis. Several immunoassays, including Western blot and in situ proximity ligation reinforced the existence of cell surface NCL-SLeA glycoforms in GC. The NCL-SLeA glycophenotype was associated with decreased survival and was not reflected in relevant healthy tissues., Conclusions: NCL-SLeA is a biomarker of poor prognosis in GC holding potential for precise cancer targeting. This is the first report describing SLeA in preferentially nuclear protein, setting a new paradigm for cancer biomarkers discovery and targeted therapies.
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- 2020
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19. Superficially Deceiving Gastric Lesion-What Lies Beneath?
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Pita I, Afonso LP, and Pimentel-Nunes P
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- Adenocarcinoma pathology, Adenocarcinoma surgery, Biopsy, Gastric Mucosa diagnostic imaging, Gastric Mucosa surgery, Humans, Male, Metaplasia diagnosis, Metaplasia pathology, Metaplasia surgery, Middle Aged, Stomach Neoplasms pathology, Stomach Neoplasms surgery, Adenocarcinoma diagnosis, Gastric Mucosa pathology, Gastroscopy, Stomach Neoplasms diagnosis
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- 2020
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20. Epstein-Barr virus is absent in gastric superficial neoplastic lesions.
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Ribeiro J, Malta M, Galaghar A, Afonso LP, Libânio D, Medeiros R, Dinis-Ribeiro M, Pimentel-Nunes P, and Sousa H
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- Aged, Carcinoma pathology, Carcinoma virology, Epstein-Barr Virus Infections complications, Epstein-Barr Virus Infections pathology, Female, Gastric Mucosa pathology, Gastric Mucosa virology, Humans, In Situ Hybridization methods, Male, Middle Aged, Retrospective Studies, Stomach pathology, Stomach Neoplasms pathology, Epstein-Barr Virus Infections virology, Herpesvirus 4, Human pathogenicity, Stomach virology, Stomach Neoplasms virology
- Abstract
Epstein-Barr virus (EBV) has been associated with about 9% of all gastric carcinomas, but its role in gastric carcinogenesis remains unclear since there is lack of evidence of EBV presence in pre-neoplastic lesions of gastric mucosa. This study intends to determine the prevalence of EBV in gastric dysplasia and superficial neoplasia to clarify whether EBV infection is an early or late event in gastric cancer development. This retrospective study included a total of 242 gastric lesions from 199 consecutive patients who were referred for endoscopic resection. The histological classification of lesions includes 137 low- and high-grade dysplasia and 105 superficial carcinomas. EBV infection was investigated by EBER-ISH. Results showed that EBV was not detected in any epithelial cells of any case with dysplasia or superficial carcinomas, although we observed the presence of a small number of EBV-infected lymphocytes in 2.1% of all lesions. These results showed that EBV is not present in gastric dysplasia neither in superficial carcinomas suggesting that EBV carcinogenesis is a late event in well/moderately differentiated gastric carcinogenesis.
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- 2019
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21. Higher IL-6 peri-tumoural expression is associated with gastro-intestinal neuroendocrine tumour progression.
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Pereira SS, Pereira R, Santos AP, Costa MM, Morais T, Sampaio P, Machado B, Afonso LP, Henrique R, and Monteiro MP
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- Adult, Aged, Aged, 80 and over, Disease Progression, Female, Humans, Intestinal Neoplasms complications, Intestinal Neoplasms pathology, Ki-67 Antigen genetics, Male, Metabolic Syndrome complications, Metabolic Syndrome pathology, Middle Aged, Neuroendocrine Tumors complications, Neuroendocrine Tumors pathology, Pancreatic Neoplasms complications, Pancreatic Neoplasms pathology, Receptor, IGF Type 1 metabolism, Stomach Neoplasms complications, Stomach Neoplasms pathology, Interleukin-6 metabolism, Intestinal Neoplasms metabolism, Metabolic Syndrome metabolism, Neuroendocrine Tumors metabolism, Pancreatic Neoplasms metabolism, Stomach Neoplasms metabolism
- Abstract
An association of well-differentiated gastroenteropancreatic neuroendocrine tumours (WD GEP NETs) with metabolic syndrome (MetS) was recently described. Yet no molecular mechanisms linking the two conditions are known. This study's aim was to identify putative molecular signatures linking WD GEP NETs and MetS to gain further insight into potential mechanisms for this association. Patients with WD GEP NETs (n=39), pancreatic (panNET) and gastro-intestinal (GI-NET), were clinically evaluated for presence of MetS. WD GEP NETs immunohistochemistry staining for Forkhead box protein M1 (FOXM1), insulin growth factor 1 receptor (IGF1R), Ki-67 and interleukin 6 (IL-6) was performed and quantified by computerised morphometric analysis. FOXM1, Ki-67, IGF1R or IL-6 expression in WD GEP NETs was not influenced by the presence of MetS. IL-6 peritumoural expression was higher in GI-NETs of patients with low HDL cholesterol (0.018±0.005% vs 0.030±0.005%, p=0.02). In GI-NETs, a higher IL-6 expression was also associated with disease progression (0.026±0.004% vs 0.016±0.002%, p=0.03). In WD GEP-NETs, MetS did not influence FOXM1, IGF1R and IL-6 expression. In GI-NETs, IL-6 expression was influenced by the MetS feature low HDL, and positively associated with disease progression. These data suggest that local and systemic inflammatory status can potentially modulate GI-NET behaviour., (Copyright © 2019 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)
- Published
- 2019
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22. Epithelioid Hemangioendothelioma Of The Internal Jugular Vein.
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Armas I, Vidoedo J, Afonso LP, Moreira A, and Abreu de Sousa J
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- Female, Hemangioendothelioma, Epithelioid diagnosis, Humans, Jugular Veins diagnostic imaging, Jugular Veins pathology, Lymph Node Excision, Middle Aged, Neoplasm Staging, Vascular Neoplasms diagnosis, Hemangioendothelioma, Epithelioid surgery, Jugular Veins surgery, Vascular Neoplasms surgery
- Abstract
Ephitelioid Hemangioendothelioma (EHE) is a rare type of tumor with vascular and sarcomatous components. There's only another case published of an internal jugular vein (IJV) EHE. A case of a 50 years-old woman with a palpable and pulsatile mass on the left cervical area is reported. Doppler ultrasound and magnetic resonance imaging showed an IVJ' 4 cm mass. Cytology was inconclusive. Surgical treatment was therefore decided and during surgery a mass inside the left IJV, with local nonsuspicious lymph nodes, was confirmed. The mass was resected including a segmental resection of the IJV and one affected tributary vessel. Lymphadenectomy of the adjacent cervical levels was performed. Histologic examination depicted an EHE without metastatic lymph nodes. Tumor was staged as pT1bN0M0 and a multidisciplinary sarcoma group proposed surveillance. Patient remained well, without evidence of disease and without complications in a twenty-four months follow-up period.
- Published
- 2019
23. Exploring sialyl-Tn expression in microfluidic-isolated circulating tumour cells: A novel biomarker and an analytical tool for precision oncology applications.
- Author
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Neves M, Azevedo R, Lima L, Oliveira MI, Peixoto A, Ferreira D, Soares J, Fernandes E, Gaiteiro C, Palmeira C, Cotton S, Mereiter S, Campos D, Afonso LP, Ribeiro R, Fraga A, Tavares A, Mansinho H, Monteiro E, Videira PA, Freitas PP, Reis CA, Santos LL, Dieguez L, and Ferreira JA
- Subjects
- Adult, Aged, Aged, 80 and over, Cell Separation, DNA Mutational Analysis, Epithelial Cell Adhesion Molecule metabolism, Female, Humans, Male, Middle Aged, Polysaccharides metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Antigens, Tumor-Associated, Carbohydrate metabolism, Biomarkers, Tumor metabolism, Medical Oncology methods, Microfluidics methods, Neoplastic Cells, Circulating metabolism, Precision Medicine methods
- Abstract
Circulating tumour cells (CTCs) originating from a primary tumour, lymph nodes and distant metastases hold great potential for liquid biopsies by providing a molecular fingerprint for disease dissemination and its temporal evolution through the course of disease management. CTC enumeration, classically defined on the basis of surface expression of Epithelial Cell Adhesion Molecule (EpCAM) and absence of the pan-leukocyte marker CD45, has been shown to correlate with clinical outcome. However, existing approaches introduce bias into the subsets of captured CTCs, which may exclude biologically and clinically relevant subpopulations. Here we explore the overexpression of the membrane protein O-glycan sialyl-Tn (STn) antigen in advanced bladder and colorectal tumours, but not in blood cells, to propose a novel CTC isolation technology. Using a size-based microfluidic device, we show that the majority (>90%) of CTCs isolated from the blood of patients with metastatic bladder and colorectal cancers express the STn antigen, supporting a link with metastasis. STn
+ CTC counts were significantly higher than EpCAM-based detection in colorectal cancer, providing a more efficient cell-surface biomarker for CTC isolation. Exploring this concept, we constructed a glycan affinity-based microfluidic device for selective isolation of STn+ CTCs and propose an enzyme-based strategy for the recovery of viable cancer cells for downstream investigations. Finally, clinically relevant cancer biomarkers (transcripts and mutations) in bladder and colorectal tumours, were identified in cells isolated by microfluidics, confirming their malignant origin and highlighting the potential of this technology in the context of precision oncology., (Copyright © 2018 Elsevier B.V. All rights reserved.)- Published
- 2019
- Full Text
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24. Clinical and pathological characterization of Epstein-Barr virus-associated gastric carcinomas in Portugal.
- Author
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Ribeiro J, Oliveira A, Malta M, Oliveira C, Silva F, Galaghar A, Afonso LP, Neves MC, Medeiros R, Pimentel-Nunes P, and Sousa H
- Subjects
- Aged, Carcinoma pathology, Carcinoma surgery, Carcinoma virology, Epstein-Barr Virus Infections pathology, Epstein-Barr Virus Infections surgery, Epstein-Barr Virus Infections virology, Female, Gastrectomy, Herpesvirus 4, Human genetics, Herpesvirus 4, Human metabolism, Humans, In Situ Hybridization, Male, Middle Aged, Portugal epidemiology, Prevalence, RNA, Small Untranslated isolation & purification, Retrospective Studies, Stomach pathology, Stomach surgery, Stomach virology, Stomach Neoplasms pathology, Stomach Neoplasms surgery, Stomach Neoplasms virology, Carcinoma epidemiology, Epstein-Barr Virus Infections epidemiology, Herpesvirus 4, Human isolation & purification, RNA, Viral isolation & purification, Stomach Neoplasms epidemiology, Viral Matrix Proteins metabolism
- Abstract
Aim: To determine the prevalence of Epstein-Barr virus (EBV)-associated gastric carcinomas in the North Region of Portugal and to study its clinicopathological characteristics., Methods: We have performed a retrospective study including a total of 179 consecutive patients with gastric cancer (GC) submitted to gastrectomy during 2011 at the Portuguese Oncology Institute of Porto. Clinical and pathological data was collected from individual clinical records and inserted on a database with unique codification. Tumour tissues were collected from the institutional tumour bank. EBV was detected by in situ hybridization for the detection of EBV-encoded small RNAs (EBERs) and EBV latent proteins (LMP1 and LMP2A) were detected by immunohistochemistry., Results: The analysis showed that EBV-associated gastric carcinomas (EBVaGC) represents 8.4% (15/179) of all GC cases, with a significant differential distribution among histological types ( P < 0.001): 100% (3/3) of medullary carcinomas, 100% (1/1) of adenosquamous carcinoma, 8.7% (8/92) of tubular adenocarcinomas, 8.0% (2/25) of mixed carcinomas and 2% (1/51) in poorly cohesive carcinomas. The analysis revealed a higher predominance of EBVaGC in the upper third and middle (cardia, fundus and body) of the stomach ( P = 0.041), a significant lower number of regional lymph nodes invasion ( P = 0.025) and a tendency for better prognosis ( P = 0.222). EBV latent protein expression revealed that all EBVaGC cases were LMP1-negative, nevertheless 6 cases (40%) expressed LPM2A, which reveals that these cases show a distinct EBV-Latency profile (latency II-like)., Conclusion: EBVaGC represents 8.4% of all GC in the North Region of Portugal. The EBV-infected patients have specific clinic-pathological features that should be further explored to develop new strategies of management and treatment., Competing Interests: Conflict-of-interest statement: Authors declare no conflict of interests in the reported study.
- Published
- 2017
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25. P53 deregulation in Epstein-Barr virus-associated gastric cancer.
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Ribeiro J, Malta M, Galaghar A, Silva F, Afonso LP, Medeiros R, and Sousa H
- Subjects
- Adult, Aged, Aged, 80 and over, Case-Control Studies, Female, Gene Expression Regulation, Neoplastic, Humans, Immunohistochemistry, Male, Middle Aged, Mutation, RNA, Messenger metabolism, Tumor Suppressor Protein p53 genetics, Epstein-Barr Virus Infections genetics, Epstein-Barr Virus Infections metabolism, Genes, p53, Herpesvirus 4, Human, Stomach Neoplasms genetics, Stomach Neoplasms metabolism, Stomach Neoplasms virology, Tumor Suppressor Protein p53 metabolism
- Abstract
TP53 is a tumour suppressor gene frequently mutated in human cancers; nevertheless, in EBV-associated malignancies mutations are uncommon despite frequent deregulation of the p53 pathway. In this study, we aimed to investigate p53 expression, TP53 mRNA levels and TP53 mutations in EBV-associated gastric carcinoma (EBVaGC). A case-control study was performed using 46 patients: 15 EBVaGC and 31 EBV-negative GC (EBVnGC) cases. p53 expression was detected by immunohistochemistry (IHC), the evaluation of p53 mRNA levels was performed by RT-qPCR and TP53 mutations were investigated only in EBVaGC cases using the DNA sanger sequencing method. p53 expression was found in 97.8% (45/46) of all gastric cancer cases (including EBVaGC and EBVnGC groups). Despite the high frequency of p53 expression in both groups, the percentages of cells are significantly higher among EBVaGC cases (p = 0.027). Regarding the mRNA levels, we found a significantly increased expression of p53 mRNA in EBVnGC (2
-ΔΔCt = 13.4 ± 2.4; p = 0.0029) when compared with EBVaGC. Furthermore, the sequencing analysis of TP53 gene revealed that only one of the 15 EBVaGC cases presented a missense mutation. Our results demonstrated that EBV-associated gastric carcinomas are characterized by a significant decrease of TP53 mRNA levels with a strong p53 expression and rare TP53 mutations when compared with EBV-negative cancers. Considering these results, EBV seems to induce a stabilization of p53 in the EBVaGC independently of the presence of mutations, which remains to be explained., (Copyright © 2017 Elsevier B.V. All rights reserved.)- Published
- 2017
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- View/download PDF
26. Neuroimaging analysis of rare brain metastases from prostate cancer: PS171 .
- Author
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Macedo J, Carneiro E, Ferreira D, Verdelho A, Afonso LP, Maurício J, Silva SM, and Arantes M
- Published
- 2017
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27. Acute administration of tramadol and tapentadol at effective analgesic and maximum tolerated doses causes hepato- and nephrotoxic effects in Wistar rats.
- Author
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Barbosa J, Faria J, Leal S, Afonso LP, Lobo J, Queirós O, Moreira R, Carvalho F, and Dinis-Oliveira RJ
- Subjects
- Analgesics, Opioid administration & dosage, Animals, Biomarkers blood, Chemical and Drug Induced Liver Injury metabolism, Chemical and Drug Induced Liver Injury pathology, Dose-Response Relationship, Drug, Injections, Intraperitoneal, Kidney metabolism, Kidney pathology, Kidney physiopathology, Kidney Diseases metabolism, Kidney Diseases pathology, Kidney Diseases physiopathology, Liver metabolism, Liver pathology, Male, Maximum Tolerated Dose, Oxidative Stress drug effects, Phenols administration & dosage, Proteinuria chemically induced, Rats, Wistar, Risk Assessment, Tapentadol, Time Factors, Tramadol administration & dosage, Analgesics, Opioid toxicity, Chemical and Drug Induced Liver Injury etiology, Glomerular Filtration Rate drug effects, Kidney drug effects, Kidney Diseases chemically induced, Liver drug effects, Phenols toxicity, Tramadol toxicity
- Abstract
Tramadol and tapentadol are two atypical synthetic opioid analgesics, with monoamine reuptake inhibition properties. Mainly aimed at the treatment of moderate to severe pain, these drugs are extensively prescribed for multiple clinical applications. Along with the increase in their use, there has been an increment in their abuse, and consequently in the reported number of adverse reactions and intoxications. However, little is known about their mechanisms of toxicity. In this study, we have analyzed the in vivo toxicological effects in liver and kidney resulting from an acute exposure of a rodent animal model to both opioids. Male Wistar rats were intraperitoneally administered with 10, 25 and 50mg/kg tramadol and tapentadol, corresponding to a low, effective analgesic dose, an intermediate dose and the maximum recommended daily dose, respectively, for 24h. Toxicological effects were assessed in terms of oxidative stress, biochemical and metabolic parameters and histopathology, using serum and urine samples, liver and kidney homogenates and tissue specimens. The acute exposure to tapentadol caused a dose-dependent increase in protein oxidation in liver and kidney. Additionally, exposure to both opioids led to hepatic commitment, as shown by increased serum lipid levels, decreased urea concentration, increased alanine aminotransferase and decreased butyrylcholinesterase activities. It also led to renal impairment, as reflected by proteinuria and decreased glomerular filtration rate. Histopathological findings included sinusoidal dilatation, microsteatosis, vacuolization, cell infiltrates and cell degeneration, indicating metabolic changes, inflammation and cell damage. In conclusion, a single effective analgesic dose or the maximum recommended daily dose of both opioids leads to hepatotoxicity and nephrotoxicity, with tapentadol inducing comparatively more toxicity. Whether these effects reflect risks during the therapeutic use or human overdoses requires focused attention by the medical community., (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Published
- 2017
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28. Effective analgesic doses of tramadol or tapentadol induce brain, lung and heart toxicity in Wistar rats.
- Author
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Faria J, Barbosa J, Leal S, Afonso LP, Lobo J, Moreira R, Queirós O, Carvalho F, and Dinis-Oliveira RJ
- Subjects
- Alanine Transaminase blood, Animals, Aspartate Aminotransferases blood, Blood Glucose analysis, Brain metabolism, Brain pathology, Caspase 3 metabolism, Creatine Kinase blood, Creatine Kinase metabolism, L-Lactate Dehydrogenase blood, L-Lactate Dehydrogenase metabolism, Lactic Acid blood, Lactic Acid metabolism, Lipid Peroxidation, Lung metabolism, Lung pathology, Male, Myocardium metabolism, Myocardium pathology, Protein Carbonylation drug effects, Rats, Wistar, Tapentadol, Analgesics, Opioid toxicity, Brain drug effects, Heart drug effects, Lung drug effects, Phenols toxicity, Tramadol toxicity
- Abstract
Tramadol and tapentadol are extensively prescribed for the treatment of moderate to severe pain. Although these drugs are very effective in pain treatment, the number of intoxications and deaths due to both opioids is increasing, and the underlying toxic mechanisms are not fully understood. The present work aimed to study the potential biochemical and histopathological alterations induced by acute effective (analgesic) doses of tramadol and tapentadol, in Wistar rats. Forty-two male Wistar rats were divided into different groups: a control, administered with normal saline solution, and tramadol- or tapentadol-treated groups (10, 25 or 50mg/kg - typical effective analgesic dose, intermediate and maximum recommended doses, respectively). 24h after intraperitoneal administration, biochemical and oxidative stress analyses were performed in blood, and specimens from brain, lung and heart were taken for histopathological and oxidative stress studies. Both drugs caused an increase in the AST/ALT ratio, in LDH, CK and CK-MB activities in serum samples, and an increase in lactate levels in serum and brain samples. Oxidative damage, namely protein oxidation, was found in heart and lung tissues. In histological analyses, tramadol and tapentadol were found to cause alterations in cell morphology, inflammatory cell infiltrates and cell death in all tissues under study, although tapentadol caused more damage than tramadol. Our results confirmed the risks of tramadol exposure, and demonstrated the higher risk of tapentadol, especially at high doses., (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
29. Long-Term Outcomes of Gastric Endoscopic Submucosal Dissection: Focus on Metachronous and Non-Curative Resection Management.
- Author
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Libânio D, Pimentel-Nunes P, Afonso LP, Henrique R, and Dinis-Ribeiro M
- Abstract
Introduction: Endoscopic submucosal dissection (ESD) is an effective treatment for gastric superficial neoplasms and curative in 80-85% of the patients. The aims of this study were to identify risk factors for non-curative resection and metachronous development, and to evaluate patient management and outcome after non-curative resection., Methods: In this single-centre study, the outcome of consecutive patients submitted to gastric ESD was assessed during a minimum follow-up of 18 months. Univariate analysis and multivariate logistic regression were performed to identify risk factors., Results: ESD was performed in 194 lesions (164 patients) between 2005 and 2014. The median follow-up was 40 months. En bloc and complete resection rates were 95.3 and 93.8%, respectively. Male sex, larger tumor size, longer procedural time, and more advanced histology were associated with a non-curative resection ( p < 0.05), but only carcinoma detected in biopsies before resection was identified as a significant risk factor on multivariate analysis. Metachronous lesions occurred in 18.4%, and the incidence rate was 4.7 lesions/100 person-years. Older age at diagnosis was identified as the only predictor of metachronous development in logistic regression. In the non-curative resection group, survival did not differ between patients allocated to surveillance and those submitted to gastrectomy; 75% of gastrectomy specimens showed no residual lesion., Conclusions: The risk factors identified for non-curative resection help to improve patient selection and patient information. Older patients had an increased risk for the development of metachronous lesions. In patients with non-curative resections, individualized patient management and surveillance seems to be an adequate option in selected cases.
- Published
- 2017
- Full Text
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30. Glycomic analysis of gastric carcinoma cells discloses glycans as modulators of RON receptor tyrosine kinase activation in cancer.
- Author
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Mereiter S, Magalhães A, Adamczyk B, Jin C, Almeida A, Drici L, Ibáñez-Vea M, Gomes C, Ferreira JA, Afonso LP, Santos LL, Larsen MR, Kolarich D, Karlsson NG, and Reis CA
- Subjects
- Glycomics, Humans, Lewis X Antigen genetics, Neoplasm Proteins genetics, Polysaccharides genetics, Receptor Protein-Tyrosine Kinases genetics, Sialyl Lewis X Antigen, Sialyltransferases biosynthesis, Sialyltransferases genetics, Stomach Neoplasms genetics, beta-Galactoside alpha-2,3-Sialyltransferase, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Lewis X Antigen biosynthesis, Neoplasm Proteins biosynthesis, Polysaccharides biosynthesis, Receptor Protein-Tyrosine Kinases metabolism, Stomach Neoplasms metabolism
- Abstract
Background: Terminal α2-3 and α2-6 sialylation of glycans precludes further chain elongation, leading to the biosynthesis of cancer relevant epitopes such as sialyl-Lewis X (SLe(X)). SLe(X) overexpression is associated with tumor aggressive phenotype and patients' poor prognosis., Methods: MKN45 gastric carcinoma cells transfected with the sialyltransferase ST3GAL4 were established as a model overexpressing sialylated terminal glycans. We have evaluated at the structural level the glycome and the sialoproteome of this gastric cancer cell line applying liquid chromatography and mass spectrometry. We further validated an identified target expression by proximity ligation assay in gastric tumors., Results: Our results showed that ST3GAL4 overexpression leads to several glycosylation alterations, including reduced O-glycan extension and decreased bisected and increased branched N-glycans. A shift from α2-6 towards α2-3 linked sialylated N-glycans was also observed. Sialoproteomic analysis further identified 47 proteins with significantly increased sialylated N-glycans. These included integrins, insulin receptor, carcinoembryonic antigens and RON receptor tyrosine kinase, which are proteins known to be key players in malignancy. Further analysis of RON confirmed its modification with SLe(X) and the concomitant activation. SLe(X) and RON co-expression was validated in gastric tumors., Conclusion: The overexpression of ST3GAL4 interferes with the overall glycophenotype of cancer cells affecting a multitude of key proteins involved in malignancy. Aberrant glycosylation of the RON receptor was shown as an alternative mechanism of oncogenic activation., General Significance: This study provides novel targets and points to an integrative tumor glycomic/proteomic-profiling for gastric cancer patients' stratification. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2016
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31. Mucosal Prolapse Polyp Mimicking Rectal Malignancy: A Case Report.
- Author
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Libânio D, Meireles C, Afonso LP, Henrique R, Pimentel-Nunes P, and Dinis-Ribeiro M
- Abstract
Mucosal prolapse polyps (MPPs) are rare inflammatory lesions that are part of the mucosal prolapse syndrome. We present the case of a 40-year-old male with history of constipation referred to our institution with suspected rectal malignancy due to hematochezia and a palpable rectal mass. Colonoscopy revealed a 25 mm wide lesion suggestive of subepithelial origin but with marked erythema and erosion in the mucosa. Crypt dilatation and distortion, mixed inflammatory infiltrate and fibrosis were apparent on histological evaluation after bite-on-bite biopsies. Due to the initial suspicion of malignancy, resection was decided after discussion with the patient. However, due to non-elevation partial resection was performed allowing the diagnosis of MPP. Hematochezia ceased after obstipation treatment and endoscopic follow-up showed maintenance of the lesion with the same characteristics except for reduced dimension. MPP may mimic neoplastic lesions and should be considered in the differential diagnosis of rectal masses. History, endoscopy and histological characteristics are all necessary and important in the diagnosis of MPP.
- Published
- 2016
- Full Text
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32. Humoral response against sialyl-Le(a) glycosylated protein species in esophageal cancer: Insights for immunoproteomic studies.
- Author
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Fernandes E, Peixoto A, Neves M, Afonso LP, Santos LL, and Ferreira JA
- Subjects
- Aged, Aged, 80 and over, Autoantibodies immunology, Biomarkers, Tumor immunology, Biomarkers, Tumor metabolism, CA-19-9 Antigen metabolism, Glycoproteins metabolism, Glycosylation, Humans, Immunity, Humoral, Immunoglobulin G blood, Immunoglobulin G metabolism, Male, Middle Aged, Esophageal Neoplasms immunology, Gangliosides metabolism, Glycoproteins immunology
- Abstract
Esophageal cancers (ECs) show poor prognosis and decreased overall survival due to late diagnosis and ineffective therapeutics, urging the introduction of novel biomarkers to aid disease management. The levels of sialyl-Lewis(a) antigen (sLe(a) ) are frequently increased in digestive tumours, which has been explored in serological non-invasive prognostication (CA19-9 test); however, with low sensitivity and specificity. Autoantibodies against cancer antigens are considered the next generation biomarkers, as they are present in circulation long before tumour-associated proteins. Based on these observations we have mined the serum of EC patients (n = 7) for antibodies against sLe(a) -glycosylated protein species. All EC were positive for sLe(a) , irrespectively of their histological nature but only two patients showed elevated CA19-9. Moreover, IgG titers, with emphasis on IgG1, were elevated in EC patients in comparison to the control group. SLe(a) -glycoproteins were then extracted from tumours of patients with negative CA19-9, isolated by immunoprecipitation and blotted with patients IgG. Autoantibodies against sLe(a) -glycosylated proteins were detected in all cases. Different SLe(a) -glycoproteins were observed for tumours of distinct histological natures, which now require identification and validation in larger patient sets. This preliminary data suggests that antoantibodies against sLe(a) glycosylated proteins hold potential for non-invasive diagnosis in CA19-9 negative cases and sets the rational for future immunoproteomic studies envisaging highly specific EC biomarkers., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2015
- Full Text
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33. Probing the O-glycoproteome of gastric cancer cell lines for biomarker discovery.
- Author
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Campos D, Freitas D, Gomes J, Magalhães A, Steentoft C, Gomes C, Vester-Christensen MB, Ferreira JA, Afonso LP, Santos LL, Pinto de Sousa J, Mandel U, Clausen H, Vakhrushev SY, and Reis CA
- Subjects
- Aged, Aged, 80 and over, Biomarkers, Tumor blood, Cell Line, Tumor, Female, Glycoproteins blood, Humans, Male, Middle Aged, N-Acetylgalactosaminyltransferases blood, Proteome, Stomach Neoplasms blood, Polypeptide N-acetylgalactosaminyltransferase, Biomarkers, Tumor metabolism, Glycoproteins metabolism, N-Acetylgalactosaminyltransferases metabolism, Stomach Neoplasms metabolism
- Abstract
Circulating O-glycoproteins shed from cancer cells represent important serum biomarkers for diagnostic and prognostic purposes. We have recently shown that selective detection of cancer-associated aberrant glycoforms of circulating O-glycoprotein biomarkers can increase specificity of cancer biomarker assays. However, the current knowledge of secreted and circulating O-glycoproteins is limited. Here, we used the COSMC KO "SimpleCell" (SC) strategy to characterize the O-glycoproteome of two gastric cancer SimpleCell lines (AGS, MKN45) as well as a gastric cell line (KATO III) which naturally expresses at least partially truncated O-glycans. Overall, we identified 499 O-glycoproteins and 1236 O-glycosites in gastric cancer SimpleCells, and a total 47 O-glycoproteins and 73 O-glycosites in the KATO III cell line. We next modified the glycoproteomic strategy to apply it to pools of sera from gastric cancer and healthy individuals to identify circulating O-glycoproteins with the STn glycoform. We identified 37 O-glycoproteins in the pool of cancer sera, and only nine of these were also found in sera from healthy individuals. Two identified candidate O-glycoprotein biomarkers (CD44 and GalNAc-T5) circulating with the STn glycoform were further validated as being expressed in gastric cancer tissue. A proximity ligation assay was used to show that CD44 was expressed with the STn glycoform in gastric cancer tissues. The study provides a discovery strategy for aberrantly glycosylated O-glycoproteins and a set of O-glycoprotein candidates with biomarker potential in gastric cancer., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)
- Published
- 2015
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34. Long-term follow-up after endoscopic resection of gastric superficial neoplastic lesions in Portugal.
- Author
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Pimentel-Nunes P, Mourão F, Veloso N, Afonso LP, Jácome M, Moreira-Dias L, and Dinis-Ribeiro M
- Subjects
- Adenocarcinoma pathology, Adult, Aged, Aged, 80 and over, Dissection adverse effects, Female, Follow-Up Studies, Gastroscopy adverse effects, Humans, Male, Middle Aged, Neoplasm, Residual, Portugal, Reoperation, Retrospective Studies, Stomach Neoplasms pathology, Survival Rate, Time Factors, Adenocarcinoma surgery, Gastric Mucosa surgery, Neoplasm Recurrence, Local etiology, Postoperative Hemorrhage etiology, Stomach Neoplasms surgery
- Abstract
Background and Study Aims: Although endoscopic resection for the treatment of gastric superficial neoplastic lesions is an established first-line treatment in Eastern countries, its role has yet to be considered in Western guidelines, mostly due to a lack of long-term studies. The aim of this study was to describe long-term outcomes for endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) in the treatment of gastric neoplasias in Portugal., Patients and Methods: This was a single-center, retrospective, cohort study between March 2003 and April 2013. A total of 162 consecutive patients with 195 gastric superficial neoplasias underwent EMR (n = 54) or ESD (n = 141) and were followed up for a median of 3.2 years., Results: Resection was feasible in 97 %, with en bloc and R0 resection rates of 85 % (94 % ESD vs. 61 % EMR; P = 0.001) and 81 % (91 % ESD vs. 54 % EMR; P < 0.001), respectively. The recurrence rate was 7 %, and recurrence was associated with Rx/R1 resection irrespective of resection technique (OR 5.8; 95 % confidence interval 3.9 - 8.8). The long-term curative resection rate was 86 % after one procedure and 91 % after two procedures. Adverse events were observed in 13 % of cases: 8 % bleeding and 2 % of perforations (EMR = ESD). Surgery was performed in 7 %: 6 % after noncurative endoscopic resection and 1 % due to complications. Metachronous lesion detection rate was 1 % - 1.5 % per patient year. Cancer-specific survival rate was 100 % at follow-up., Conclusions: For the first time in a Western country, results are reported to be similar to those in Eastern countries. Endoscopic resection, particularly ESD, is a highly effective treatment for gastric superficial lesions, without compromising cancer survival. Endoscopic resection should also be considered as first-line treatment for gastric neoplasias in Western countries., (© Georg Thieme Verlag KG Stuttgart · New York.)
- Published
- 2014
- Full Text
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35. Association between environmental factors and CDX2 expression in gastric cancer patients.
- Author
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Peleteiro B, Lunet N, Wen X, Afonso LP, Mendes N, Barros R, Carneiro F, Almeida R, and Barros H
- Subjects
- Adenocarcinoma microbiology, Aged, CDX2 Transcription Factor, Cell Differentiation, Female, Helicobacter Infections, Helicobacter pylori, Humans, Intestinal Mucosa metabolism, Life Style, Male, Middle Aged, Risk Factors, Signal Transduction, Stomach Neoplasms microbiology, Surveys and Questionnaires, Adenocarcinoma metabolism, Biomarkers, Tumor metabolism, Environmental Exposure, Homeodomain Proteins metabolism, Stomach Neoplasms metabolism
- Abstract
Intestinal differentiation, mediated by CDX2, may occur both in intestinal and in diffuse gastric carcinomas. In an attempt to ascertain the environmental determinants of the intestinal differentiation pathway, we aimed to compare the exposure to environmental factors in gastric cancer cases according to the CDX2 expression status. We evaluated 270 patients undergoing gastrectomy due to gastric adenocarcinoma. Cases were classified according to tumour location within the stomach, Laurén's histological type and CDX2 expression. Participants completed a comprehensive structured questionnaire on sociodemographic and behavioural characteristics and provided a blood sample for assessment of Helicobacter pylori infection status. Odds ratios with 95% confidence intervals were computed by unconditional logistic regression to compare cancer cases according to histological type and CDX2 expression status. Approximately 80% of the patients expressed CDX2, regardless of the histological type and location of the tumour. No statistically significant or consistent associations between sociodemographic or environmental exposures and CDX2 expression status were observed, except for a decreased risk of CDX2 expression in those with higher coffee consumption for tumours of the intestinal type (≥ 1 vs. <1 cup/day: odds ratio =0.36, 95% confidence interval: 0.13-0.97). In conclusion, this is the first study to use CDX2 expression as a finer marker of intestinal differentiation to distinguish aetiologically distinct subgroups of gastric cancer, adding new evidence to the previous research on the determinants of cancer of Laurén's intestinal and diffuse types.
- Published
- 2012
- Full Text
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36. MSI phenotype and MMR alterations in familial and sporadic gastric cancer.
- Author
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Leite M, Corso G, Sousa S, Milanezi F, Afonso LP, Henrique R, Soares JM, Castedo S, Carneiro F, Roviello F, Oliveira C, and Seruca R
- Subjects
- Adaptor Proteins, Signal Transducing genetics, Aged, DNA-Binding Proteins genetics, Female, Humans, Male, Middle Aged, MutL Protein Homolog 1, MutS Homolog 2 Protein genetics, Nuclear Proteins genetics, Phenotype, Stomach Neoplasms metabolism, Gene Expression Regulation, Neoplastic, Microsatellite Instability, Microsatellite Repeats, Promoter Regions, Genetic, Stomach Neoplasms genetics
- Abstract
Microsatellite instability (MSI) is a major pathway involved in gastric carcinogenesis occurring in 20% of gastric cancer (GC). However, it is not clear whether MSI phenotype preferentially occurs in the sporadic or familial GC, when stringent inclusion criteria are used. The aim of this study was to compare the frequency of MSI and hypermethylation of MLH1 promoter in a large series of familial GC patients (non-HNPCC and non-CDH1-related) and sporadic cases. Additionally, we analysed the immunoexpression of MMR proteins in a fraction of cases. Overall, the frequency of familial GC was 7.1%, and the frequency of hereditary tumours was 4.6%. MSI phenotype and MLH1 hypermethylation frequencies were not statistical different between familial and sporadic GC settings. Further, the MSI phenotype was not associated with any clinico-pathological features studied in the familial GC setting, whereas in the sporadic setting, it was associated with older age, female gender and intestinal histotype. Using our stringent Amsterdam-based clinical criteria to select familial GC (number of cases, age of onset), we verified that sporadic and familial cases differed in gender but shared histopathological features. We verified that the frequency of MSI was similar in familial and sporadic GC settings, demonstrating that this molecular phenotype is not a hallmark of familial GC in contrast to what is verified in HNPCC. Moreover, we observed that the frequency of MLH1 hypermethylation is similar in sporadic and familial cases suggesting that in both settings MSI is not associated to MMR genetic alterations but in contrast to epigenetic deregulation., (Copyright © 2010 UICC.)
- Published
- 2011
- Full Text
- View/download PDF
37. Rhizomucor and scedosporium infection post hematopoietic stem-cell transplant.
- Author
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Marques DS, Pinho Vaz C, Branca R, Campilho F, Lamelas C, Afonso LP, Jacome M, Breda E, Monteiro E, and Campos Júnior A
- Abstract
Hematopoietic stem-cell transplant recipients are at increased risk of developing invasive fungal infections. This is a major cause of morbidity and mortality. We report a case of a 17-year-old male patient diagnosed with severe idiopathic acquired aplastic anemia who developed fungal pneumonitis due to Rhizomucor sp. and rhinoencephalitis due to Scedosporium apiospermum 6 and 8 months after undergoing allogeneic hematopoietic stem-cell transplant from an HLA-matched unrelated donor. Discussion highlights risk factors for invasive fungal infections (i.e., mucormycosis and scedosporiosis), its clinical features, and the factors that must be taken into account to successfully treat them (early diagnosis, correction of predisposing factors, aggressive surgical debridement, and antifungal and adjunctive therapies).
- Published
- 2011
- Full Text
- View/download PDF
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