Detection of Sepsis in Platelets Using MicroRNAs and Membrane Antigens.

The present study proposes to legitimize in sepsis a characteristic found in platelets that suffer storage lesions in blood banks, which is the increased expression of miRNA miR-320a in relation to miR-127. Under physiologically normal conditions, an inverse relationship is observed. The aim of this study was to verify whether the analysis of miR-320a and miR-127 expression in platelets could detect a decrease in their viability and function due to the presence of pathogens in the blood of patients hospitalized in the Intensive Care Unit. We also investigated the expression of membrane antigens sensitive to platelet activation. Of the 200 patients analyzed, only those who developed sepsis (140) were found to have a higher relative quantity of miR-320a than that of miR-127. This characteristic and the increased expression of membrane antigens P2Y12, CD62P, CD41, and CD61 showed a significant association (p < 0.01) with all types of sepsis evaluated in this study. Additionally, 40% of patients hospitalized for sepsis had negative results for the first cultures. We conclude that analysis of miR-127 and miR-320a expression combined with membrane antigens evaluation, in association with the available clinical and diagnostic parameters, are important tools to detect the onset of sepsis.

Telomerase (hTERT) Overexpression Reveals a Promising Prognostic Biomarker and Therapeutical Target in Different Clinical Subtypes of Pediatric Acute Lymphoblastic Leukaemia.

Acute Lymphoblastic Leukemia (ALL) is a neoplasm of the hematopoietic system defined as a clonal expansion of an abnormal lymphoid precursor cell. It mostly affects children under five years of age and is the most common tumor to afflict pediatric patients. The expression of the human telomerase gene (hTERT) in patients with ALL has been studied as a biomarker and could become a new therapeutic target. We evaluate the role of hTERT gene expression in ALL pediatric patients, through quantitative real-time PCR technique, and the possible correlation between hTERT expression and clinical variables: gender, age, white blood cells (WBC), gene fusions, and immunophenotyping. The analysis between healthy controls and ALL patients (N = 244) was statistically significant (p < 0.001), demonstrating hTERT overexpression in these patients. In comparison with the usual set of clinical variables, the data were not statistically significant (p > 0.05), indicating that hTERT is equally overexpressed among patients regardless of gender, age, gene fusions, and immunophenotyping. Moreover, patients who presented a higher hTERT expression level had a significant (p < 0.0001) lower overall survival rate. In summary, hTERT expression emerges as an important molecular pathway in leukemogenesis regardless patient's clinical variables, thus, the data here presented pointed it as a valuable biomarker in pediatric acute lymphoblastic leukemia and a promising target for new therapeutic and prognostic measures.

PD-L1 Expression Associated with Epstein-Barr Virus Status and Patients' Survival in a Large Cohort of Gastric Cancer Patients in Northern Brazil.

Gastric cancer (GC) is a worldwide health problem, making it one of the most common types of cancer, in fifth place of all tumor types, and the third highest cause of cancer deaths in the world. There is a subgroup of GC that consists of tumors infected with the Epstein-Barr virus (EBV) and is characterized mainly by the overexpression of programmed cell death protein-ligand-1 (PD-L1). In the present study, we present histopathological and survival data of a thousand GC patients, associated with EBV status and PD-L1 expression. Of the thousand tumors analyzed, 190 were EBV-positive and the vast majority (86.8%) had a high relative expression of mRNA and PD-L1 protein (p < 0.0001) in relation to non-neoplastic control. On the other hand, in EBV-negative samples, the majority had a low PD-L1 expression of RNA and protein (p < 0.0001). In the Kaplan-Meier analysis, the probability of survival and increased overall survival of EBV-positive GC patients was impacted by the PD-L1 overexpression (p < 0.0001 and p = 0.004, respectively). However, the PD-L1 low expression was correlated with low overall survival in those patients. Patients with GC positive for EBV, presenting PD-L1 overexpression can benefit from immunotherapy treatments and performing the quantification of PD-L1 in gastric neoplasms should be adopted as routine.

Analysis of Increased EGFR and IGF-1R Signaling and Its Correlation with Socio-Epidemiological Features and Biological Profile in Breast Cancer Patients: A Study in Northern Brazil.

INTRODUCTION: Breast cancer (BC) is the second most frequent cancer worldwide. It is known that a subset of BC has amplification, and overexpression of the epidermal growth factor receptor (EGFR) and high expression of the insulin-like growth factor receptor-1 (IGF-1R) are correlated with a favorable prognosis. This study aimed to evaluate the prognostic and predictive values of the EGFR and IGF-1R in tumor samples from patients with BC and their correlation with socio-epidemiological features. PATIENTS AND METHODS: We analyzed socio-epidemiological, clinical-pathological data and tumor tissues from 124 patients with BC undergoing treatment, to assess levels of EGFR and IGF-1R mRNA and protein. The predictive performance included the calculation of area-under-the-curve (AUC) to discriminate groups of patients with high and low mRNA expression associated with survival analysis within each molecular group of BC. RESULTS: We found a significant expression increase (p <0.001) in EGFR associated with body mass index, angiolymphatic invasion, compromised lymph nodes and follow-up in 58.1% of the triple-negative and HER overexpression tumors. The increase in IGF-IR was significant (p <0.001) in 41.9% of luminal tumors A and B. ROC analysis showed that EGFR had a higher predictive performance (AUC = 0.891) than IGF-1R (AUC = 0.60). The Kaplan-Meier analysis indicated that only the high expression of EGFR was associated with a decreased probability of survival for patients, what did not happen with IGF-1R. CONCLUSION: Our results suggest that EGFR and IGF-1R expression patterns associated with the clinical characteristics of patients and biological profile influenced the evolution of BC.

Copy Number Alterations in Papillary Thyroid Carcinomas: Does Loss of SESN2 Have a Role in Age-related Different Prognoses?

BACKGROUND/AIM: Thyroid cancer is the only tumor in which age is an important prognostic factor. In papillary thyroid carcinomas (PTC), 45 years of age seems to be a key point that divides adult patients into two groups, with different clinical features. The aim of the study was to perform a microarray-based analysis in two groups of patients (<45 and ≥45 years old), in order to verify the occurrence of specific copy number alterations (CNAs) that could be associated to different patient behaviors associated with age. PATIENTS AND METHODS: In order to search and compare genomic alterations that may be related to age, we evaluated the occurrence of CNAs in the genome of 24 PTC samples, divided in two groups (<45 and ≥45 years old). RESULTS: We identified only one region showing a statistically significant difference between the groups (p=0.00357): a deletion of approximately 537 kps in 1p35.3., which was more frequent in patients aged 45 years or older. This is the region where, among others, the gene SESN2 is located, which is activated under oxidative stress and plays an antioxidant role, in addition to protecting the genetic material from damage generated by reactive oxygen species (ROS). CONCLUSION: This is the first time that a CNA involving the deletion of the SESN2 gene is associated with papillary thyroid carcinomas, particularly in patients aged 45 years and older, indicating that this deletion would lead to a more malignant and prominent tumoral behavior associated to a worst prognosis.

Establishment of Drug-resistant Cell Lines as a Model in Experimental Oncology: A Review.

Many types of cancer are initially susceptible to chemotherapy, but during treatment, patients may develop resistance to therapy. Knowing that acquisition of drug resistance is a major clinical problem in antineoplastic treatment, the present work aimed to present, through a literature review, the development of chemoresistant cells lines as a model in experimental oncology. A total of 110 drug-resistant cell lines, mainly from lung tumors and leukemias, have been developed. In addition, it has been observed that the drugs used for induction of resistance represented the drugs used for first-line treatment of each neoplasia, since the ideal chemotherapeutic treatment to induce resistance in vitro aims at a better modulation of the therapeutic response in order to better study the mechanisms of resistance.