Browsing by Author "Faria, Gil"
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- Colon tumor CD31 expression is associated with higher disease-free survival in patients with metabolic syndromePublication . Silva, Ana; Pereira, Sofia S.; Brandão, José Ricardo; Brochado, Paulo; Monteiro, Mariana P.; Araújo, António; Faria, GilMetabolic syndrome (MS) is recognized as a risk factor for colon cancer (CC). However, how does the interplay between metabolic dysfunction caused by MS and its individual components affect CC microenvironment and prognosis remains unexplored. Angiogenesis and lymphangiogenesis are fundamental processes for tumor progression and dissemination, ensuring oxygen and nutrient delivery and supporting one of the most important pathways of tumor dissemination, contributing to metastasis. Thus, our aim was to evaluate whether the expression of molecular biomarkers involved in angiogenic and lymphangiogenic processes influenced CC clinicopathological features and prognosis in patients with MS. Clinical and pathological data of 300 patients submitted to CC surgical resection at a single tertiary hospital were retrospectively retrieved from hospital records. Tumor tissue microarrays of archived paraffin-embedded blocks were used to assess CD31, VEGF-A and D2–40 tissue expression by immunohistochemistry. The percentage of stained area was quantified by computerized morphometric analysis. No association between tissue expression of angiogenesis and lymphangiogenesis biomarkers and tumor clinical and pathological characteristics was found. However, in subgroup analysis of patients with MS, dysglycemia was associated with lower D2–40 expression (p = 0.007) and high waist-circumference was associated with higher D2–40 (p = 0.0029) and VEGF-A expression (p = 0.026). In an adjusted Cox proportional hazard model CD31 expression was significantly associated with greater disease-free survival (HR=0.62; 95% CI: 0.41–0.95, p = 0.028). No association was found between D2–40 and VEGF-A expression and CC prognosis. Our data reinforces previous reports that suggest the potential use of CD31 as a CC prognostic biomarker. Additionally, our data further supports the evidence for an interplay between metabolic dysfunction, tumor microenvironment, and vascularization pathways.
- Effect of metabolic syndrome and individual components on colon cancer characteristics and prognosisPublication . Silva, Ana; Pereira, Sofia S.; Monteiro, Mariana P.; Araújo, António; Faria, GilMetabolic syndrome (MS) is recognized as a risk factor for colon cancer (CC). However, whether the cluster of metabolic changes that define MS also influence CC prognosis remains unclear. Thus, our aim was to investigate whether the presence of MS or any of the MS individual components could provide prognostic information on tumor phenotype and survival outcomes. Clinical and pathological data from patients with CC (n = 300) who underwent surgical resection at a single tertiary hospital were retrospectively collected to evaluate presence of MS components and diagnostic criteria, CC phenotype and disease outcomes. Patients were allocated into two groups according to the presence or absence of MS (n = 85 MS vs n = 83 non-MS). The overall prevalence of MS individual components was 82.7% for increased waist-circumference (WC), 61.3% for high blood pressure (BP), 48.8% for low HDL-cholesterol, 39.9% for high fasting glucose, and 33.9% for hypertriglyceridemia. Patients in the MS group presented smaller tumors (p = 0.006) with lower T-stage (p = 0.002). High BP (p = 0.029) and hypertriglyceridemia (p = 0.044) were associated with a smaller tumor size, while low-HDL (p = 0.008) was associated with lower T-stage. After propensity score matching using age, tumor size and staging as covariates high-BP (p = 0.020) and WC (p = 0.003) were found to influence disease-free survival, but not overall survival. In conclusion, despite MS being an established risk factor for CC, our data does not support the hypothesis that MS components have a negative impact on disease extension or prognosis. Nevertheless, a protective role of BP and lipid lowering drugs cannot be excluded.
- Impact of adiposity on staging and prognosis of colorectal cancerPublication . Silva, Ana; Faria, Gil; Araújo, António; Monteiro, Mariana P.Abdominal visceral fat is a well-recognized a risk for colorectal cancer (CRC). In contrast to the risk for CRC, the impact of adiposity in disease staging and patient survival is less well-established. Our aim was to critically review the literature on the influence of adiposity assessed by different methods routinely used in clinical settings, on CRC staging and prognosis. In the 32 studies reviewed, overweight was initially identified as a survival advantage, an evidence that was later challenged by studies suggesting that body adiposity is likely to have a deleterious effect in CRC outcomes, particularly in males. Hence, whether obesity has a negative impact in CRC staging or prognosis remains controversial. In sum, addressing the impact of body fat in CRC biological behavior is still an unmet need. Understanding how adiposity influences CRC staging and prognosis could allow further patient risk stratification for devising targeted interventions and improve clinical outcomes.
- Inflammatory and Cardiometabolic Risk on Obesity: Role of Environmental XenoestrogensPublication . Teixeira, Diana; Pestana, Diogo; Santos, Cristina; Correia-Sá, Luísa; Marques, Cláudia; Norberto, Sónia; Meireles, Manuela; Faria, Ana; Silva, Ricardo; Faria, Gil; Sá, Carla; Freitas, Paula; Taveira-Gomes, António; Domingues, Valentina; Delerue-Matos, Cristina; Calhau, Conceição; Monteiro, RosárioContext: Some chemicals used in consumer products or manufacturing (eg, plastics, pesticides) have estrogenic activities; these xenoestrogens (XEs) may affect immune responses and have recently emerged as a new risk factors for obesity and cardiovascular disease. However, the extent and impact on health of chronic exposure of the general population to XEs are still unknown. Objective: The objective of the study was to investigate the levels of XEs in plasma and adipose tissue (AT) depots in a sample of pre- and postmenopausal obese women undergoing bariatric surgery and their cardiometabolic impact in an obese state. Design and Participants: We evaluated XE levels in plasma and visceral and subcutaneous AT samples of Portuguese obese (body mass index ≥ 35 kg/m2) women undergoing bariatric surgery. Association with metabolic parameters and 10-year cardiovascular disease risk was assessed, according to menopausal status (73 pre- and 48 postmenopausal). Levels of XEs were determined by gas chromatography with electron-capture detection. Anthropometric and biochemical data were collected prior to surgery. Adipocyte size was determined on tissue sections obtained during surgery. Results: Our data show that XEs are pervasive in this obese population. Distribution of individual and concentration of total XEs differed between plasma, visceral AT, and subcutaneous AT, and the pattern of accumulation was different between pre- and postmenopausal women. Significant associations between XE levels and metabolic and inflammatory parameters were found. In premenopausal women, XEs in plasma seem to be a predictor of 10-year cardiovascular disease risk. Conclusions: Our findings point toward a different distribution of XE between plasma and AT in pre- and postmenopausal women, and reveal the association between XEs on the development of metabolic abnormalities in obese premenopausal women
- Optimization and validation of organochlorine compounds in adipose tissue by SPE-gas chromatographyPublication . Fernandes, Virgínia C.; Pestana, Diogo; Monteiro, Rosário; Faria, Gil; Meireles, Manuela; Correia-Sá, Luísa; Teixeira, Diana; Faria, Ana; Calhau, Conceição; Domingues, Valentina F.; Delerue-Matos, CristinaScientific evidence has shown an association between organochlorine compounds (OCC) exposure and human health hazards. Concerning this, OCC detection in human adipose samples has to be considered a public health priority. This study evaluated the efficacy of various solid-phase extraction (SPE) and cleanup methods for OCC determination in human adipose tissue. Octadecylsilyl endcapped (C18-E), benzenesulfonic acid modified silica cation exchanger (SA), poly (styrene-divinylbenzene (EN) and EN/RP18 SPE sorbents were evaluated. The relative sample cleanup provided by these SPE columns was evaluated using gas chromatography with electron capture detection (GC–ECD). The C18-E columns with strong homogenization were found to provide the most effective cleanup, removing the greatest amount of interfering substance, and simultaneously ensuring good analyte recoveries higher than 70%. Recoveries>70% with standard deviations (SD)<15% were obtained for all compounds under the selected conditions. Method detection limits were in the 0.003–0.009 mg/kg range. The positive samples were confirmed by gas chromatography coupled with tandem mass spectrometry (GC-MS/MS). The highest percentage found of the OCC in real samples corresponded to HCB, o,p′-DDT and methoxychlor, which were detected in 80 and 95% of samples analyzed respectively. Copyright © 2012 John Wiley & Sons, Ltd.
- Persistent organic pollutant levels in human visceral and subcutaneous adipose tissue in obese individuals - Depot differences and dysmetabolism implicationsPublication . Pestana, Diogo; Faria, Gil; Sá, Carla; Fernandes, Virgínia C.; Teixeira, Diana; Norberto, Sónia; Faria, Ana; Meireles, Manuela; Marques, Cláudia; Correia-Sá, Luísa; Cunha, Ana; Guimarães, João T.; Taveira-Gomes, António; Santos, Ana Cristina; Domingues, Valentina F.; Delerue-Matos, Cristina; Monteiro, Rosário; Calhau, ConceiçãoBackground: The role of persistent organic pollutants (POPs) with endocrine disrupting activity in the aetiology of obesity and other metabolic dysfunctions has been recently highlighted. Adipose tissue (AT) is a common site of POPs accumulation where they can induce adverse effects on human health. Objectives: To evaluate the presence of POPs in human visceral (vAT) and subcutaneous (scAT) adipose tissue in a sample of Portuguese obese patients that underwent bariatric surgery, and assess their putative association with metabolic disruption preoperatively, as well as with subsequent body mass index (BMI) reduction. Methods: AT samples (n=189) from obese patients (BMI ≥35) were collected and the levels of 13 POPs were determined by gas chromatography with electron-capture detection (GC-ECD). Anthropometric and biochemical data were collected at the time of surgery. BMI variation was evaluated after 12 months and adipocyte size was measured in AT samples. Results: Our data confirm that POPs are pervasive in this obese population (96.3% of detection on both tissues), their abundance increasing with age (RS=0.310, p<0.01) and duration of obesity (RS=0.170, p<0.05). We observed a difference in AT depot POPs storage capability, with higher levels of ΣPOPs in vAT (213.9±204.2 compared to 155.1±147.4 ng/g of fat, p<0.001), extremely relevant when evaluating their metabolic impact. Furthermore, there was a positive correlation between POP levels and the presence of metabolic syndrome components, namely dysglycaemia and hypertension, and more importantly with cardiovascular risk (RS=0.277, p<0.01), with relevance for vAT (RS=0.315, p<0.01). Finally, we observed an interesting relation of higher POP levels with lower weight loss in older patients. Conclusion: Our sample of obese subjects allowed us to highlight the importance of POPs stored in AT on the development of metabolic dysfunction in a context of obesity, shifting the focus to their metabolic effects and not only for their recognition as environmental obesogens.
- Visceral obesity is associated with lower stage colon tumors in males without survival advantagePublication . Silva, Ana; Gomes, Francisco; S. Pereira, Sofia; P. Monteiro, Mariana; Araújo, António; Faria, GilVisceral obesity and systemic inflammatory response (SIR) were suggested to be closely related to colon cancer (CC) oncological and surgical outcomes. The first by producing several soluble factors involved in carcinogenesis and the second for having a key role in the nutritional and functional decline of patients with cancer. Furthermore, gender differences in relative body composition and adipose tissue regional distribution have also been acknowledged to influence CC. The primary aim of this study was to determine whether visceral adiposity, stratified by gender, influenced CC staging and prognosis. As secondary aim, this study evaluated whether visceral adiposity and SIR markers were associated with CC pathological features so that these could be used in clinical practice to predict disease outcomes and potentially influence therapeutic decisions. Case records from patients (n = 300) submitted to CC surgical resection at a single tertiary hospital were retrospectively reviewed to retrieve clinical, laboratory, imaging and pathological data. Visceral fat area was quantified by computerized morphometric analysis in preoperative tomography scans. Visceral obesity was defined as visceral fat area ≥160 cm2 for men and ≥80 cm2 for women. Preoperative full blood count performed as part of the routine clinical assessment at the hospital laboratory was used to obtain C-reactive protein (CRP) levels and to calculate neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), which were used as SIR markers. One hundred and forty-three (n = 143) patients fulfilled eligibility criteria and were included in the analysis. Patients with high-visceral adipose tissue (vAT) had smaller size CC tumors (p < 0.001), earlier T-stage disease (p = 0.027) and lower nodal involvement (p = 0.039). In gender subgroup analysis, these findings were only confirmed in males. Moreover, male patients with high-vAT also had a lower proportion of metastatic nodes (p = 0.021) and metastatic to dissected lymph node ratio (p = 0.030). Additionally, patients with high-vAT also had lower PLR (p = 0.001). CC survival was not influenced by visceral obesity, gender nor SIR. In conclusion, our study shows that male patients with high visceral adiposity have lower PLR levels and earlier stage tumors. Furthermore, our data suggests that visceral obesity and SIR despite being associated with earlier stage CC tumors do not seem to present a survival advantage.