Oncolytic alphavirus-induced extracellular vesicles counteract the immunosuppressive effect of melanoma-derived extracellular vesicles.

Extracellular vesicles (EVs)-mediated communication by cancer cells contributes towards the pro-tumoral reprogramming of the tumor microenvironment. Viral infection has been observed to alter the biogenesis and cargo of EVs secreted from host cells in the context of infectious biology. However, the impact of oncolytic viruses on the cargo and function of EVs released by cancer cells remains unknown.

Altered galectin-3 distribution and migratory function in the pre-diabetic non-obese diabetic mouse thymus.

Galectin-3 is an endogenous lectin which binds mainly to β-galactosides on the cell surface and extracellular matrix (ECM) glycoproteins. In the thymus, this lectin is constitutively expressed, being involved in thymocyte adhesion, migration, and death. Galectin-3 has been related to type 1 diabetes, an autoimmune disease characterized by pancreatic β-cell destruction mediated by autoreactive T lymphocytes.

Mannose-6-Phosphate Isomerase Functional Status Shapes a Rearrangement in the Proteome and Degradome of Mannose-Treated Melanoma Cells.

Metabolic reprogramming is a ubiquitous feature of transformed cells, comprising one of the hallmarks of cancer and enabling neoplastic cells to adapt to new environments. Accumulated evidence reports on the failure of some neoplastic cells to convert mannose-6-phosphate into fructose-6-phosphate, thereby impairing tumor growth in cells displaying low levels of mannose-6-phosphate isomerase (MPI). Thus, we performed functional analyses and profiled the proteome landscape and the repertoire of substrates of proteases (degradome) of melanoma cell lines with distinct mutational backgrounds submitted to treatment with mannose.

Data-driven, cross-disciplinary collaboration: lessons learned at the largest academic health center in Latin America during the COVID-19 pandemic.

Introduction: The COVID-19 pandemic has prompted global research efforts to reduce infection impact, highlighting the potential of cross-disciplinary collaboration to enhance research quality and efficiency.

Methods: At the FMUSP-HC academic health system, we implemented innovative flow management routines for collecting, organizing and analyzing demographic data, COVID-related data and biological materials from over 4,500 patients with confirmed SARS-CoV-2 infection hospitalized from 2020 to 2022. This strategy was mainly planned in three areas: organizing a database with data from the hospitalizations; setting-up a multidisciplinary taskforce to conduct follow-up assessments after discharge; and organizing a biobank.

Polymorphisms in transcription factor binding sites and enhancer regions and pancreatic ductal adenocarcinoma risk.

Genome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratification and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict significance threshold commonly used makes it likely that many true risk loci are missed. Functional annotation of GWAS polymorphisms is a proven strategy to identify additional risk loci.

Prognostic Impact of Primary Tumor Sidedness in Stage III Colorectal Cancer: Real-World Evidence from a Brazilian Cohort.

Background: Primary tumor sidedness (PTS) is an independent prognostic factor in patients with metastatic colorectal cancer (CRC), with a worse prognosis for right-sided tumors. There are limited data on the prognostic impact of PTS in stage III CRC. The main objective of this study was to analyze the prognostic impact of PTS in stage III CRC.

Aerobic exercise training mitigates tumor growth and cancer-induced splenomegaly through modulation of non-platelet platelet factor 4 expression.

Exercise training reduces the incidence of several cancers, but the mechanisms underlying these effects are not fully understood. Exercise training can affect the spleen function, which controls the hematopoiesis and immune response. Analyzing different cancer models, we identified that 4T1, LLC, and CT26 tumor-bearing mice displayed enlarged spleen (splenomegaly), and exercise training reduced spleen mass toward control levels in two of these models (LLC and CT26).

A novel program of infiltrative control in astrocytomas: ADAM23 depletion promotes cell invasion by activating -secretase complex.

Background: Infiltration is a life-threatening growth pattern in malignant astrocytomas and a significant cause of therapy resistance. It results in the tumor cell spreading deeply into the surrounding brain tissue, fostering tumor recurrence and making complete surgical resection impossible. We need to thoroughly understand the mechanisms underlying diffuse infiltration to develop effective therapies.

Development of a Prognostic Model for Early Breast Cancer Integrating Neutrophil to Lymphocyte Ratio and Clinical-Pathological Characteristics.

Background: Breast cancer-related inflammation is critical in tumorigenesis, cancer progression, and patient prognosis. Several inflammatory markers derived from peripheral blood cells count, such as the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII) are considered as prognostic markers in several types of malignancy.

Methods: We investigate and validate a prognostic model in early patients with breast cancer to predict disease-free survival (DFS) based on readily available baseline clinicopathological prognostic factors and preoperative peripheral blood-derived indexes.

deltaXpress (ΔXpress): a tool for mapping differentially correlated genes using single-cell qPCR data.

Background: High-throughput experiments provide deep insight into the molecular biology of different species, but more tools need to be developed to handle this type of data. At the transcriptomics level, quantitative Polymerase Chain Reaction technology (qPCR) can be affordably adapted to produce high-throughput results through a single-cell approach. In addition to comparative expression profiles between groups, single-cell approaches allow us to evaluate and propose new dependency relationships among markers.

A scan of all coding region variants of the human genome, identifies 13q12.2-rs9579139 and 15q24.1-rs2277598 as novel risk loci for pancreatic ductal adenocarcinoma.

Coding sequence variants comprise a small fraction of the germline genetic variability of the human genome. However, they often cause deleterious change in protein function and are therefore associated with pathogenic phenotypes. To identify novel pancreatic ductal adenocarcinoma (PDAC) risk loci, we carried out a complete scan of all common missense and synonymous SNPs and analysed them in a case-control study comprising four different populations, for a total of 14 538 PDAC cases and 190 657 controls.

Expression data of FOS and JUN genes and FTIR spectra provide diagnosis of thyroid carcinoma.

We explore the feasibility of using FOS and JUN gene expression and ATR-FTIR for diagnosis of thyroid cancer. For the study, 38 samples (6 non-neoplastic (NN), 10 papillary thyroid carcinoma (PTC), 7 follicular thyroid carcinoma (FTC), and 15 benign tumors (BT) were subjected to RNA extraction followed by quantitative real time PCR (qRT-PCR) and 30 samples (5 NN, 9 PTC, 5 FTC, and 11 BT) were used for Attenuated Total Reflectance - Fourier Transform Infrared (ATR-FTIR) followed by multivariate analysis. Of the above, 20 samples were used for both gene expression and ATR-FTIR studies.

Deciphering the Functional Status of Breast Cancers through the Analysis of Their Extracellular Vesicles.

Breast cancer (BC) accounts for the highest incidence of tumor-related mortality among women worldwide, justifying the growing search for molecular tools for the early diagnosis and follow-up of BC patients under treatment. Circulating extracellular vesicles (EVs) are membranous nanocompartments produced by all human cells, including tumor cells. Since minimally invasive methods collect EVs, which represent reservoirs of signals for cell communication, these particles have attracted the interest of many researchers aiming to improve BC screening and treatment.

Screening of Exosome-Derived Proteins and Their Potential as Biomarkers in Diagnostic and Prognostic for Pancreatic Cancer.

In the oncological area, pancreatic cancer is one of the most lethal diseases, with 5-year survival rising just 10% in high-development countries. This disease is genetically characterized by as a driven mutation followed by , , and -associated mutations. In clinical aspects, pancreatic cancer presents unspecific clinical symptoms with the absence of screening and early plasmatic biomarker, being that CA19-9 is the unique plasmatic biomarker having specificity and sensitivity limitations.

Insights from a Computational-Based Approach for Analyzing Autophagy Genes across Human Cancers.

In the last decade, there has been a boost in autophagy reports due to its role in cancer progression and its association with tumor resistance to treatment. Despite this, many questions remain to be elucidated and explored among the different tumors. Here, we used omics-based cancer datasets to identify autophagy genes as prognostic markers in cancer.

Anticoagulant Activity of Nucleic Acid Nanoparticles (NANPs) Assessed by Thrombin Generation Dynamics on a Fully Automated System.

Rapidly reversible anticoagulant agents have great clinical potential. Oligonucleotide-based anticoagulant agents are uniquely positioned to fill this clinical niche, as they are able to be deactivated through the introduction of the reverse complement oligo. Once the therapeutic and the antidote oligos meet in solution, they are able to undergo isothermal reassociation to form short, inactive, duplexes that are rapidly secreted via filtration by the kidneys.

Reverse Transfection of Functional RNA Rings into Cancer Cells Followed by in Vitro Irradiation.

RNA nanoparticles are promising therapeutic platforms to improve radiotherapy since they can be functionalized with multiple small interfering RNAs (RNAi) to simultaneously silence critical radioresistance genes. Here we describe the transfer of RNA rings to mammalian cancer cells through reverse transfection, followed by in vitro irradiation and biological assays as surrogates' endpoints for radiotherapy efficacy.

Phomactinine, the First Nitrogen-Bearing Phomactin, Produced by sp. CBMAI 1333.

Metabolomics analyses and improvement of growth conditions were applied toward diversification of phomactin terpenoids by the fungus sp. CBMAI 1333. Visualization of molecular networking results on Gephi assisted the observation of phomactin diversification and guided the isolation of new phomactin variants by applying a modified version of chemometrics based on a fractional factorial design.

Extracellular Vesicle-Packaged miR-195-5p Sensitizes Melanoma to Targeted Therapy with Kinase Inhibitors.

Management of advanced melanoma remains challenging, with most BRAF (B-Raf proto-oncogene, serine/threonine kinase)-mutated metastatic patients relapsing within a few months upon MAPK inhibitors treatment. Modulation of tumor-derived extracellular vesicle (EVs) cargo with enrichment of antitumoral molecules is a promising strategy to impair tumor progression and increase treatment response. Herein, we report that restored expression of miR-195-5p, down-regulated in melanoma favoring drug resistance, increases the release of EVs enriched in the tumor suppressor miRNAs, miR-195-5p, miR-152-3p, and miR-202-3p.