Patricia Severino

Hospital Israelita Albert Einstein | IIEPAE · Centro de Estudo e Pesquisa

Alternative splicing is the process of generating different mRNAs from the same primary transcript, which contributes to increase the transcriptome and proteome diversity. Abnormal splicing has been associated with the development of several diseases including cancer. Given that mutations and abnormal levels of the RIPK2 transcript and RIP-2 protei...

Inflammation is characterized by a biphasic cycle consisting initially of a proinflammatory phase that is subsequently resolved by anti-inflammatory processes. Interleukin-1β (IL-1β) is a master regulator of proinflammation and is encoded within the same topologically associating domain (TAD) as IL-37, which is an anti-inflammatory cytokine that op...

8554 Background: Surgery is standard of care for patients with stage I non-small cell lung cancer (NSCLC). However, 5-year mortality can reach up to 30%. For patients with contraindication to surgery, treatment with stereotactic ablative radiotherapy (SABR) leads to adequate local tumor control, but has a high rate of regional and distant failure....

Metabolomics has proven to be an important omics approach to understand the molecular pathways underlying the tumour phenotype and to identify new clinically useful markers. The literature on cancer has illustrated the potential of this approach as a diagnostic and prognostic tool. The present study aimed to analyse the plasma metabolic profile of...

HPV infection is one of the most important risk factors for head and neck squamous cell carcinoma among younger patients. Y RNAs are short non-coding RNAs involved in DNA replication. Y RNAs have been found to be dysregulated in many cancers, including head and neck squamous cell carcinoma (HNSCC). In this study we have investigated the role of Y R...

Klebsiella pneumoniae is considered an opportunistic pathogen frequently involved with healthcare-associated infections. The genome of K. pneumoniae is versatile, harbors diverse virulence factors and easily acquires and exchanges resistance plasmids, facilitating the emergence of new threatening clones. In the last years, ST16 has been described a...

Background Healthcare-associated infections by carbapenem-resistant Klebsiella pneumoniae are difficult to control. Virulence and antibiotic resistance genes contribute to infection, but the mechanisms associated with the transition from colonization to infection remain unclear. Objective We investigated the transition from carriage to infection b...

Despite breakthroughs in precision medicine during the past decade due to bulk RNA profiling approaches, those conceal gene expression heterogeneity expected in samples and tissues. Recent developments in single-cell RNA sequencing (scRNA-seq) have enabled researchers to dissect this heterogeneity through genome-wide expression profiling at cellula...

Abstract Background Human papilloma virus infection is known to influence oropharyngeal cancer (OPC) risk, likely via sexual transmission. However, sexual behaviour has been correlated with other risk factors including smoking and alcohol, meaning independent effects are difficult to establish. We aimed to evaluate the causal effect of sexual behav...

Background: MicroRNAs and their role in cancer have been extensively studied for the past decade. Here, we analyzed the biological role and diagnostic potential of miR-154-5p and miR-154-3p in head and neck squamous cell carcinoma (HNSCC). Methods: miRNA expression analyses were performed using The Cancer Genome Atlas (TCGA) data accessed from cBio...

Extracellular vesicles (EVs) are mediators of the immune system response. Encapsulated in EVs, microRNAs can be transferred between cancer and immune cells. To define the potential effects of EVs originated from squamous cell carcinoma cells on immune system response, we performed microRNA profiling of EVs released from two distinct cell lines and...

Human papilloma virus infection is known to influence oropharyngeal cancer (OPC) risk, likely via sexual transmission. However, sexual behaviour has been correlated with other risk factors including smoking and alcohol, meaning independent effects are difficult to establish. Here we evaluate aspects of sexual behaviour in relation to the risk of OP...

Objectives Investigate the DNA copy number and the methylation profile of the homeobox genes HOXA5, HOXA7, HOXA9, HOXB5, HOXB13, HOXC12, HOXC13, HOXD10, HOXD11, IRX4 and ZHX1, and correlate them clinicopathological parameters and overall survival. Material and methods DNA from OSCC samples and surgical margins were submitted to DNA amplification b...

Head and neck squamous cell carcinoma (HNSCC), which includes cancers of the oral cavity and oropharynx, is a cause of substantial global morbidity and mortality. Strategies to reduce disease burden include discovery of novel therapies and repurposing of existing drugs. Statins are commonly prescribed for lowering circulating cholesterol by inhibit...

Klebsiella pneumoniae carbapenemase (KPC) actively hydrolyzes carbapenems, antibiotics often used a last-line treatment for multidrug-resistant bacteria. KPC clinical relevance resides in its widespread dissemination. In this work, we report the genomic context of KPC coding genes blaKPC-2, blaKPC-3 and blaKPC-30 in multidrug-resistant Klebsiella p...

Introduction Head and neck squamous cell carcinoma (HNSCC), which includes cancers of the oral cavity and oropharynx, is a cause of substantial global morbidity and mortality. Strategies to reduce disease burden include discovery of novel therapies and repurposing of existing drugs. Statins are commonly prescribed for lowering circulating cholester...

Mesenchymal Stromal Cells (MSCs) are being targeted for diverse cell-therapies applications. The MSC expansion in bioreactor is necessary to achieve the cell number required for clinical applications in accordance with cGMP guidelines. Since the culture conditions may influence the post-expansion MSC outcomes, in this work, human Umbilical Cord Mat...

Pseudomonas aeruginosa is a ubiquitous microorganism and an important opportunistic pathogen responsible for a broad spectrum of infections mainly in immunosuppressed and critically ill patients. Molecular investigations traditionally rely on pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). In this work we propose a co...

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic stem cell diseases characterized by dysplasia of one or more hematologic lineages and a high risk of developing into acute myeloid leukemia. MDS patients have recurrent bacterial infections and abnormal expression of CD56 by monocytes. We investigated MDS patients' bone marr...

Natural triterpenes exhibit a wide range of biological activities. Since this group of secondary metabolites is structurally diverse, effects may vary due to distinct biochemical interactions within biological systems. In this work, we investigated the anticancer-related activities of the quinone-methide triterpene maytenin and its derivative compo...

In vitro drug screening is widely used in the development of new drugs, because they constitute a cost-effective approach to select compounds with more potential for therapy. They are also an attractive alternative to in vivo testing. However, most of these assays are done in two-dimensional culture models, where cells are grown on a polystyrene or...

Bacterial resistance is a severe threat to global public health. Exposure to sub-lethal concentrations has been considered a major driver of mutagenesis leading to antibiotic resistance in clinical settings. Ciprofloxacin is broadly used to treat infections caused by Pseudomonas aeruginosa, whereas increased mutagenesis induced by sub-lethal concen...

Among the clinical manifestations observed in septic patients, sepsis-associated encephalopathy (SAE) is probably the most obscure and poorly explored. It is well established, however, that SAE is more prevalent in aged individuals and related to a worse outcome. In this context, we decided to investigate the acute effects of sepsis, induced by cec...

Receptor-interacting proteins are a family of serine/threonine kinases, which integrate extra and intracellular stress signals caused by different factors, including infections, inflammation and DNA damage. Receptor-interacting serine/threonine-protein kinase 2 (RIP-2) is a member of this family and an important component of the nuclear factor NF-k...

Pseudomonas aeruginosa is an important opportunistic pathogen in hospitals, responsible for various infections that are difficult to treat due to intrinsic and acquired antibiotic resistance. Here, twenty epidemiologically unrelated strains isolated from patients in a general hospital over a time period of two decades were analyzed using whole geno...

Squamous cell carcinomas (SCCs) remain among the most common malignancies of the head and neck region. Plasma microRNAs (miRNAs) are appealing biomarker candidates for diagnosis or therapy response monitoring since they may be associated with clinical and pathological features of the disease. Increasing evidence also points to a role for these mole...

Antimicrobial peptides possess a myriad of molecular properties including bacterial killing and the regulation of many aspects of innate immunity. Cathelicidins are a group of antimicrobial peptides widely investigated by the scientific community. Many studies have focused on the bactericidal and pro-inflammatory roles of cathelicidins. Because the...

MicroRNAs are small noncoding RNAs that play important roles in cellular biology. They have been implicated in pharmacogenomics by down-regulating genes that are essential for drug function. In this work we verified the potential anticancer activity of the quinone methide triterpenes maytenin and 22-β-hydroxymaytenin, as well as of a quinone methid...

Lymph node (LN) is a secondary lymphoid organ with highly organized structure. Fibroblastic reticular cells (FRCs) integrate LN structure, and are characterized by podoplanin expression (PDPN, gp38) and lack of CD31. FRCs are involved in several immune response processes but the mechanism is still under investigation. Another cell population presen...

Lymph node (LN) is a secondary lymphoid organ with highly organized and compartmentalized structure. LNs harbor B, T, and other cells among fibroblastic reticular cells (FRCs). FRCs are characterized by both podoplanin (PDPN/gp38) expression and by the lack of CD31 expression. FRCs are involved in several immune response processes but mechanisms un...

Double-negative cell (DNC) and fibroblastic reticular cell (FRC) sorting purity. (A) Stromal cells isolated from lymph nodes were sorted in two populations, (B,C) DNCs and, (D–F) FRCs according to gp38/PDPN expression. After DNCs and FRCs expansion in culture and before each experiment, gp38/PDPN expression was verified, and when purity was lower t...

Gate strategy for monocytes, dendritic cells, and lymphocytes. (A) Monocytes were gated on FSC vs CD14, followed by CD14 vs CD33, and the double-positive cells were analyzed for CD80, CD86, CD209, and HLA-DR, (B) immature and, (C) mature dendritic cells were gated on FSC vs CD14, followed by CD14 vs CD33, and the CD14-CD33 + positive cells were ana...

Histopathology of human lymph nodes (LNs). (A) LN derived from larynx cancer patient LN04, (B) LNs derived from liver donor LN16. (C) LN derived from diverticulitis LN12 hematoxylin–eosin (HE) immunostaining show the organ integrity LN immunohistochemistry for CD3, CD20, or CD68 show the presence of T lymphocytes (CD3), B lymphocytes (CD20), and ma...

Sepsis is a major cause of death and its incidence and mortality increase exponentially with age. Most gene expression studies in sepsis have focused in protein-coding genes and the expression patterns, and potential roles of long noncoding RNAs (lncRNAs) have not been investigated yet. In this study, we performed co-expression network analysis of...

Squamous cell carcinoma of the head and neck is one of the most common cancer types worldwide. It initiates on the epithelial lining of the upper aerodigestive tract, at most instances as a consequence of tobacco and alcohol consumption. Treatment options based on conventional therapies or targeted therapies under development have limited efficacy...

Antimicrobial peptides are an ancient family of molecules that emerged millions of years ago and have been strongly conserved during the evolutionary process of living organisms. Recently, our group described that the human antimicrobial peptide LL-37 migrates to the nucleus, raising the possibility that LL-37 could directly modulate transcription...

Antimicrobial peptides are an ancient family of molecules that emerged millions of years ago and have been strongly conserved during the evolutionary process of living organisms. Recently, our group described that the human antimicrobial peptide LL-37 migrates to the nucleus, raising the possibility that LL-37 could directly modulate transcription...

MicroRNAs are small non-coding RNA molecules with roles in gene expression regulation and implications in cancer initiation and progression. Cell-free microRNAs detected in body fluids, and in particular in plasma, are of clinical interest due to their possible use as biomarkers. Despite the fact that their reliable quantification depends on severa...

Lymph node is a secondary lymphoid organ with highly organized and compartmentalized structure. Fibroblastic reticular cells (FRC) integrate LN structure, and are characterized by podoplanin expression (PDPN) and lack of CD31. FRCs are involved in several immune response processes but the mechanism is still under investigation. Another cell populat...

Lymph node is a secondary lymphoid organ with highly organized and compartmentalized structure. Fibroblastic reticular cells (FRC) integrate LN structure, and are characterized by podoplanin expression (PDPN) and lack of CD31. FRCs are involved in several immune response processes but the mechanism is still under investigation. Another cell populat...

Lymph node is a secondary lymphoid organ with highly organized and compartmentalized structure. Fibroblastic reticular cells (FRC) integrate LN structure, and are characterized by podoplanin expression (PDPN) and lack of CD31. FRCs are involved in several immune response processes but the mechanism is still under investigation. Another cell populat...

The total amount of scientific literature has grown rapidly in recent years. Specifically, there are several million citations in the field of cancer. This makes it difficult, if not impossible, to manually retrieve relevant information on the mechanisms that govern tumor behavior or the neoplastic process. Furthermore, cancer is a complex disease...

Sepsis is an especially common affliction in the elderly and despite its increased prevalence and mortality in older people, the immune response of the elderly during septic shock appears similar to that of younger patients. In the original study we conducted a global gene expression analysis of circulating neutrophils from elderly and young septic...

Small noncoding RNAs are regulatory molecules that play important roles in several aspects of cellular biology. They vary from 18 to 30 nucleotides in length and often act through the inactivation of complementary sequences. A variety of small RNA classes have been identified to date and the list is constantly growing, owing to the advent of new se...

Small non-coding regulatory RNAs control cellular functions at the transcriptional and post-transcriptional levels. Oral squamous cell carcinoma is among the leading cancers in the world and the presence of cervical lymph node metastases is currently its strongest prognostic factor. In this work we aimed at finding small RNAs expressed in oral squa...

Sepsis is one of the highest causes of mortality in hospitalized people and a common complication in both surgical and clinical patients admitted to hospital for non-infectious reasons. Sepsis is especially common in older people and its incidence is likely to increase substantially as a population ages. Despite its increased prevalence and mortali...

Despite low mortality rates, nodal recurrence in papillary thyroid carcinoma occurs in up to 20 % of patients. Emerging evidences indicate that dysregulated microRNAs are implicated in the process of metastasis. In the present study, we investigated whether miR-9, miR-10b, miR-21 and miR-146b levels are predictive of papillary thyroid carcinoma rec...

Small noncoding RNAs are important transcriptional regulators implicated in several aspects of cell biology. Recent studies have demonstrated that qualitative and quantitative information on these molecules may be clinically useful for the cancer community. Next-Generation Sequencing is quickly becoming the technology of choice to study their role...

Hemophilia A, B, and von Willebrand disease correspond to more than 90% of all inherited bleeding disorders associated with coagulation factor deficiencies. Symptoms between these deficiencies may vary greatly and yet are often phenotypically similar. Bleeding episodes can range from mild to severe, at times with life threatening hemorrhages. Curre...

Homeobox genes are a family of transcription factors that play a pivotal role in embryogenesis. Prospero homeobox 1 (PROX1) has been shown to function as a tumor suppressor gene or oncogene in various types of cancer, including oral squamous cell carcinoma (OSCC). We have previously identified PROX1 as a downregulated gene in OSCC. The aim of this...

Mechanisms governing the inflammatory response during sepsis involve crosstalk between diverse signaling pathways, but current knowledge provides an incomplete picture of the syndrome. Microarray-based expression profiling is a powerful approach for the investigation of complex clinical conditions such as sepsis. In this study, we investigated whol...

MicroRNAs are small noncoding RNAs involved in the initiation and progression of human cancers. Squamous cell carcinoma of the head and neck is among the leading cancers in the world, whereas suitable screening markers or personalized therapy are currently unavailable. MicroRNAs are being tackled as biomarkers with potential to improve outcomes of...

Mechanisms governing the inflammatory response during sepsis have been shown to be complex, involving cross-talk between diverse signaling pathways. Current knowledge regarding the mechanisms underlying sepsis provides an incomplete picture of the syndrome, justifying additional efforts to understand this condition. Microarray-based expression prof...

Burkitt lymphoma (BL) is an aggressive B-cell lymphoma more common in children comprising one third of pediatric non-Hodgkin lymphoma cases. The recent discovery in BL pathogenesis highlighted the activation of PI3K pathway in cooperation with Myc in the development of BL. In this study, we demonstrated that PI3K/Akt pathway is a target to histone...

Recently, molecular biology has been substantially improved by the development of new technologies that allow the assessment of the genome, transcriptome and proteome on a high-throughput scale and at reasonable costs. The translation of all the information generated by these technologies into new biomarkers is an enormous challenge for the biomedi...

Current evidence implicates aberrant microRNA expression patterns in human malignancies; measurement of microRNA expression may have diagnostic and prognostic applications. Roles for microRNAs in head and neck squamous cell carcinomas (HNSCC) are largely unknown. HNSCC, a smoking-related cancer, is one of the most common malignancies worldwide but...

The implication of post-transcriptional regulation by microRNAs in molecular mechanisms underlying cancer disease is well documented. However, their interference at the cellular level is not fully explored. Functional in vitro studies are fundamental for the comprehension of their role; nevertheless results are highly dependable on the adopted cell...

Dendritic cells (DCs) are antigen (Ag)-presenting cells that activate and stimulate effective immune responses by T cells, but can also act as negative regulators of these responses and thus play important roles in immune regulation. Pro-angiogenic vascular endothelial growth factor (VEGF) has been shown to cause defective DC differentiation and ma...