Two Different Immune Profiles Are Identified in Sentinel Lymph Nodes of Early-Stage Breast Cancer.

In the management of early-stage breast cancer (BC), lymph nodes (LNs) are typically characterised using the One-Step Nucleic Acid Amplification (OSNA) assay, a standard procedure for assessing subclinical metastasis in sentinel LNs (SLNs). The pivotal role of LNs in coordinating the immune response against BC is often overlooked. Our aim was to improve prognostic information provided by the OSNA assay and explore immune-related gene signatures in SLNs.

Promoting advanced medical services in the framework of 3PM-a proof-of-concept by the "Centro" Region of Portugal.

Unlabelled: Multidisciplinary team from three universities based in the "Centro" Region of Portugal developed diverse approaches as parts of a project dedicated to enhancing and expanding Predictive, Preventive, and Personalized Medicine (3PM) in the Region. In a sense, outcomes acted as a proof-of-concept, in that they demonstrated the feasibility, but also the relevance of the approaches. The accomplishments comprise defining a new regional strategy for implementing 3PM within the Region, training of human resources in genomic sequencing, and generating good practices handbooks dedicated to diagnostic testing via next-generation sequencing, to legal and ethical concerns, and to knowledge transfer and entrepreneurship, aimed at increasing literacy on 3PM approaches.

Influence of clinical factors on the protective or deleterious impact of genetic variants in orthodontically induced external root resorption: an observational study.

Background: Prediction of susceptibility to Orthodontically Induced External Apical Root Resorption (OIEARR) has been hampered by the complex architecture of this multifactorial phenotype. The aim of this study was to analyze the impact of the interaction of multiple variables in the susceptibility to OIEARR.

Methods: The study evaluated 195 patients requiring orthodontic treatment.

Clinical and Genetic Risk Factors for Drug-Induced Liver Injury Associated with Anti-Tuberculosis Treatment-A Study from Patients of Portuguese Health Centers.

Drug-induced liver injury (DILI) is an unpredictable and feared side effect of antituberculosis treatment (AT). The present study aimed to identify clinical and genetic variables associated with susceptibility to AT-associated hepatotoxicity in patients with pulmonary tuberculosis treated with a standard protocol. Of 233 patients enrolled, 90% prospectively, 103 developed liver injury: 37 with mild and 66 with severe phenotype (DILI).

Antagonistic effect of IL1 variants in periodontitis and external apical root resorption: Evidence from a literature review.

External apical root resorption (EARR) induced by orthodontic treatment and chronic periodontitis (CP) are complex phenotypes dependent on the interaction of multiple genetic and non-genetic risk factors. Apart from different environmental triggers, these phenotypes are caused by antagonistic biological mechanisms involving local immunoinflammatory reaction and alveolar bone metabolism, for which IL1 have a prominent role. Whereas EARR benefits from bone remodelling, CP is characterized by osteolytic damaged.

Impairment of breast cancer cell invasion by COX-2-specific inhibitor NS398: roles of CXCR4 and of uPA system.

Inhibition of cyclooxygenase-2 (COX-2) is known to impair cancer cell metastatic behaviour, but the mechanisms involved largely remain elusive. We aimed to analyse whether the antimetastatic effect of COX-2 inhibition in breast cancer cells could be explained by variations in the expression levels of chemokine receptor CXCR4, vascular endothelium growth factor (VEGF) and UPA/UPAR components of the urokinase plasminogen activator system (uPAR). Breast cancer cell line MDA-MB-231 was exposed to COX-2-specific inhibitor NS398.

CYP1A1 m1 and m2 polymorphisms: genetic susceptibility to lung cancer.

Lung cancer is considered an environment-related disease that develops as a consequence of exposure to mutagenic agents, namely those present in tobacco. The CYP1A1 gene codifies the phase I enzyme aryl hydrocarbon hydroxilase (AHH) belonging to the cytochrome P450 system that plays a major role in the bio-activation of tobacco procarcinogenes. Two CYP1A1 polymorphisms, m1 (T6235C transition) and m2 (A4889G transition), are associated with greater enzymatic activity and have been described as genetic susceptibility factors for lung cancer.

TP53 germline mutations in Portugal and genetic modifiers of age at cancer onset.

The Li-Fraumeni syndrome (LFS) is a rare, autosomal dominant disease caused by TP53 germline mutations. This study aimed to characterize the TP53 mutational spectrum in patients suspected to have LFS in Portugal and to evaluate the influence of the MDM2-SNP309 and TP53-72Arg variants and of telomere length on age of tumor onset. Probands were primarily selected using the classical LFS criteria (two cases) or the more sensitive Chompret Li-Fraumeni-like (LFL) criteria (13 cases), but 12 additional patients that did not comply with those LFS or LFL criteria were included in the analysis based on clinical suspicion (LFS suspects).

Lack of association of vitamin D receptor gene polymorphisms with susceptibility to type 1 diabetes mellitus in the Portuguese population.

The vitamin D receptor (VDR) gene is a candidate gene for susceptibility to autoimmune disorders. Association studies of VDR polymorphisms and risk of type 1 diabetes often produced conflicting results in different ethnic backgrounds. The aim of this study was to test for association between common VDR polymorphisms and the genetic susceptibility to type 1 diabetes in the Portuguese population.

The phenotypical and functional characteristics of cord blood monocytes and CD14(-/low)/CD16(+) dendritic cells can be relevant to the development of cellular immune responses after transplantation.

Umbilical cord blood (UCB) has been used as an alternative source of haematopoietic progenitors for transplantation presenting advantages over bone marrow (BM) that are related with known shortages of newborns' immune system at adaptive and innate levels. Using flow cytometry, we studied the expression of Toll-like receptors (TLRs) and chemokine receptors (CKRs) and the production of pro-inflammatory cytokines by monocytes and CD14(-/low)/CD16(+)DCs from peripheral blood (PB; n=10), and umbilical cord blood (UCB; n=10). CKRs and cytokines were studied before and after stimulation of cells with LPS plus IFN-gamma.

Genetic polymorphism of CYP2D6 influences susceptibility to papillary thyroid cancer.

Objective: Xenobiotic-metabolizing enzymes are widely polymorphic and confer interindividual variation in the ability to detoxify carcinogens or to activate pro-carcinogens. A common polymorphism of cytochrome P450 2D6 (CYP2D6) results in lack of enzyme activity and has been associated with an altered susceptibility to several cancers. The aim of this study was to investigate the association between the CYP2D6 poor metaboliser genotype and the risk of papillary thyroid cancer (PTC).

PROP1 gene analysis in Portuguese patients with combined pituitary hormone deficiency.

Objective: Mutations of the PROP1 gene lead to combined pituitary hormone deficiency (CPHD), which is characterized by a deficiency of GH, TSH, LH/FSH, PRL and, less frequently, ACTH. This study was undertaken to investigate the molecular defect in a cohort of patients with CPHD.

Design, Patients And Measurements: A multicentric study involving 46 cases of CPHD (17 familial cases belonging to seven kindreds and 29 sporadic cases) selected on the basis of clinical and hormonal evidence of GH deficiency, central hypothyroidism and hypogonadotrophic hypogonadism, in the absence of an identified cause of hypopituitarism.

Molecular detection of EGFRvIII-positive cells in the peripheral blood of breast cancer patients.

The aim of this study is to evaluate epidermal growth factor receptor variant III, EGFRvIII, a cancer specific mutant, as a possible marker for the diagnosis of breast cancer occult systemic disease. EGFRvIII mRNA was identified by an RT-nested PCR with a high sensitivity. In 102 women studied, the mutant was detected in the peripheral blood of 30% of 33 low risk, early stage patients, in 56% of 18 patients selected for neoadjuvant chemotherapy, in 63.

BRCA1 and BRCA2 germline mutational spectrum and evidence for genetic anticipation in Portuguese breast/ovarian cancer families.

We present the first characterisation of the mutational spectrum of the entire coding sequences and exon-intron boundaries of the BRCA1 and BRCA2 genes as well as large BRCA1 rearrangements in Portuguese families with inherited predisposition to breast/ovarian cancer. Of the 100 probands studied, pathogenic mutations were identified in 22 (24.7%) of 89 breast and/or ovarian cancer families with more than one affected member (15 in BRCA1 and seven in BRCA2), but in none of the 11 patients without family history of cancer.

CYP2D6 genetic polymorphisms are associated with susceptibility to pituitary tumors.

Several polymorphisms of drug-metabolizing enzymes have been implicated in the susceptibility to tumor development. The role of the CYP2D6, GSTM1 and GSTT1 genes has been extensively studied, with alleles conferring different metabolic efficiencies and tumor risk. We studied the relationship between the main polymorphisms of these genes and the susceptibility to develop pituitary tumors, by performing a case-control study comprising 235 patients and 256 controls which were genotyped by means of PCR-RFLP based assays.

Germline MUTYH (MYH) mutations in Portuguese individuals with multiple colorectal adenomas.

Germinal mutations in the base excision repair (BER) gene MUTYH (MYH) have recently been described in association with predisposition to multiple colorectal adenomas and cancer. In contrast to the classic dominant condition of familial adenomatous polyposis (FAP) due to germinal mutations in the APC gene, the MYH polyposis is an autosomal recessive disease. The identification of individuals affected by MYH polyposis brings new and important implications for the diagnostic, screening, genetic counseling, follow up and therapeutic options in these patients.

E-Cadherin (CDH1) and p53 rather than SMAD4 and Caspase-10 germline mutations contribute to genetic predisposition in Portuguese gastric cancer patients.

Approximately 30% of all hereditary diffuse gastric cancer (HDGC) families carry CDH1 germline mutations. The other two thirds remain genetically unexplained and are probably caused by alterations in other genes. Using polymerase chain reaction (PCR)/single-strand conformation polymorphism (SSCP)/sequencing, we screened 32 Portuguese families with a history of gastric cancer and 23 patients with early onset gastric cancer for CDH1 germline mutations.

Immunophenotypic and functional characterization of cord blood dendritic cells.

Dendritic cells (DCs) play a pivotal role in the activation of T cells, which are effector cells in graft-versus-host disease (GVHD). A low incidence of GVHD following cord blood (CB) transplantation has long been reported; despite this, little information is currently available on the characteristics of CB DCs. The goal of the present study was to investigate the immunophenotypic characteristics and distribution of CB DCs and their subsets.

Molecular diagnosis of Huntington disease in Portugal: implications for genetic counselling and clinical practice.

Huntington disease (HD) is a neurodegenerative, autosomal dominant disorder of late-onset, caused by the expansion of a CAG repeat in the coding region of the gene. Ours is the reference laboratory for genetic testing in HD, in Portugal, since 1998; 90.1% of all 158 families known were identified for the first time, including patients with unusual presentation or without family history.

Early onset of medullary thyroid carcinoma in a kindred with multiple endocrine neoplasia type iia associated with cutaneous lichen amyloidosis.

Objective: To describe the molecular characterization of a kindred affected by the rare variant of multiple endocrine neoplasia type IIA (MEN IIA) associated with cutaneous lichen amyloidosis and to discuss the clinical implications in the management of this syndrome.

Methods: A kindred with four affected family members was identified, and DNA analysis was performed by sequencing exon 11 of the RET proto-oncogene. Presymptomatic genetic screening was offered to all first-degree relatives.