Ana Rita Castro

Macrophages from IBD patients exhibit defective tumour necrosis factor-α secretion but otherwise normal or augmented pro-inflammatory responses to infection.

Defects in macrophage function have been implicated in the establishment of Crohns disease (CD). However, the response of macrophages from CD patients to live bacteria, particularly Mycobacterium avium subsp. paratuberculosis (MAP), has not been addressed. Considering MAP has long been associated to CD, our objective was to assess whether macrophages from CD patients showed impaired inflammatory response to infection by MAP comparing to M. avium subsp. avium (MA) and other live intestinal commensal bacteria. Human peripheral blood monocyte-derived macrophages were obtained from CD patients, ulcerative colitis (UC) patients and controls. Following in vitro infection with MAP, MA, Escherichia coli or Enterococcus faecalis, cytokine levels and cell surface receptor expression were evaluated at different time points. Macrophages from CD patients showed impaired TNF-α secretion in response to bacterial challenge, but augmented IL-23 secretion and preserved IL-12 secretion and CD-40 expression. In addition, CD macrophages showed low IL-10 secretion. Macrophages from IBD patients showed increased expression of TLR-2 and -4, unaffected by infection. Differences in cytokine secretion observed after bacterial challenge were not MAP-specific, as other bacteria (E. coli and MA) showed similar effects. Macrophages from UC patients showed a less compromised TNF-α synthesis in response to mycobacterial infection than CD macrophages, with increased constitutive IL-12 secretion, and preserved IL-10 secretion. The increased IL-23 levels in response to infection and decreased IL-10 production observed in macrophages from CD patients may contribute to the inflammatory exacerbation observed in those patients.

Sialyl-Tn identifies muscle-invasive bladder cancer basal and luminal subtypes facing decreased survival, being expressed by circulating tumor cells and metastases

OBJECTIVESnTo evaluate the potential of sialyl-Tn (STn), a cancer-associated glycan antigen present in membrane glycoproteins, to improve a recent molecular model for stratification and prognostication of advanced stage bladder tumors based on keratins (KRT14, 5, and 20) expression. In addition, determine the association between STn and disease dissemination based on the evaluation of circulating tumor cells (CTCs) and the metastasis, which is a critical matter to improve patient management.nnnPATIENTS AND METHODSnA retrospective series of 80 muscle-invasive primary bladder tumors and associated metastasis were screened for KRT14, 5, and 20 and STn by real-time polymerase chain reaction and immunohistochemistry. Peripheral blood was collected in a patients subset, CTCs were isolated through a size-based microfluidic chip and screened for KRTs and STn.nnnRESULTSnBasal-like lesions presented worse cancer-specific and disease-free survival compared to luminal tumors. STn antigen inclusion discriminated patients with worst survival in each subgroup (P = 0.047 for luminal; P = 0.027 for basal-like tumors). STn expression in CTCs and distant metastasis was also demonstrated.nnnCONCLUSIONnThis work reinforces the potential of the KRT-based model for bladder cancer management and the association of STn with aggressiveness, supporting its inclusion in predictive molecular models toward patient-tailored precision medicine. Moreover, we describe for the first time that CTCs and the metastasis present a basal phenotype and express the STn antigen, highlighting its link with disease dissemination. Future studies should focus on determining the biological and clinical significance of these observations in the context of liquid biopsies. Given the membrane nature of STn, highly specific targeted therapeutics may also be envisaged.

MS237 SERUM ATHEROGENIC LIPID MARKERS IN SUBJECTS FROM THREE ISLANDS OF THE AZORES' ARCHIPELAGO (PORTUGAL) – A COMPARISON STUDY

Objective: To study the relation between smoking habit and cardiovascular risk in a Northern Greek population sample. Method: 3000 subjects (54% males and 46% females) with mean age 62±13 years from Northern Greece were examined during an epidemiological project the last three years. All subjects gave informed consent form and completed a questionnaire on personal and family medical history. Demographic/anthropometric characteristics and blood pressure were recorded. Biochemical parameters (total cholesterol, HDL, LDL, triglycerides) were measured by the Cholestech Kit (dry chemistry method). All subjects were divided into three groups according to smoking habit: current smokers, ex smokers and non smokers. SPSS 15.0 was used for the epidemiological analysis. Data are presented as mean±standard deviation. Results: Most of the subjects studied were non smokers (74.1%). Smoking habit was more frequent in men than in women (65/35% respectively) and in younger ages (47±14 years) with a mean smoking duration of 16±6 years. Dyslipidemia and hypertension were the strongest risk factors in all three groups. Atheromatic index and cardiovascular risk score were higher in the current smokers group (4.7±1.6 and 21% respectively). Conclusions: Smoking habit found to be strongly related to the overall cardiovascular risk whereas smoking cessation reduced it greatly. Most of the ex smokers had quit smoking due to health problems such as diabetes, dyslipidemia, coronary artery disease and hypertension. Today every smoker should be considered as a patient examined thoroughly for the existence of other risk factors and be advised to follow a smoking cessation program.