p.R337H Germline Variant among Women at Risk of Hereditary Breast Cancer in a Public Health System of Midwest Brazil.

Despite the high prevalence of pathogenic variants (PV) carriers in the South and Southeast regions of Brazil, germline genetic testing for hereditary breast cancer (HBC) is not available in the Brazilian public health system, and the prevalence of Li-Fraumeni syndrome (LFS) is not well established in other regions of Brazil. We assessed the occurrence of p.R337H carriers among women treated for breast cancer (BC) between January 2021 and January 2022 at public hospitals of Brasilia, DF, Brazil.

Next-generation sequencing profiling of miRNAs in individuals with 22q11.2 deletion syndrome revealed altered expression of miR-185-5p.

Background: The 22q11.2 deletion syndrome (22q11.2DS) is a microdeletion syndrome with highly variable phenotypic manifestations, even though most patients present the typical 3 Mb microdeletion, usually affecting the same ~ 106 genes.

miR-9-5p is Downregulated in Serum Extracellular Vesicles of Patients Treated with Biperiden After Traumatic Brain Injury.

Traumatic brain injury (TBI) is a prevalent and debilitating condition, which often leads to the development of post-traumatic epilepsy (PTE), a condition that yet lacks preventive strategies. Biperiden, an anticholinergic drug, is a promising candidate that has shown efficacy in murine models of PTE. MicroRNAs (miRNAs), small regulatory RNAs, can help in understanding the biological basis of PTE and act as TBI- and PTE-relevant biomarkers that can be detected peripherally, as they are present in extracellular vesicles (EVs) that cross the blood-brain barrier.

The bladder microbiota is not significantly altered by intravesical BCG therapy.

Introduction: Bladder microbiota dysbiosis has been associated with several urological disorders. However, dysbiosis markers in bladder cancer have not been identified and little is known about the effect of Bacillus Calmette-Guérin (BCG) intravesical therapy on the bladder microbiota. In this study, we compared the bladder microbiota of patients with non-muscle-invasive bladder cancer (NMIBC) undergoing BCG therapy to nononcological controls.

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.

Longitudinal analysis at three oral sites links oral microbiota to clinical outcomes in allogeneic hematopoietic stem-cell transplant.

The oral cavity is the ultimate doorway for microbes entering the human body. We analyzed oral microbiota dynamics in allogeneic hematopoietic stem-cell transplant recipients and showed that microbiota injury and recovery patterns were highly informative on transplant complications and outcomes. Our results highlight the importance of tracking the recipient's microbiota changes during allogeneic hematopoietic stem-cell transplant to improve our understanding of its biology, safety, and efficacy.

Urinary microbiota is associated to clinicopathological features in benign prostatic hyperplasia.

Background: The urinary microbiota of patients with benign prostatic hyperplasia (BPH) has been associated with lower urinary tract symptoms (LUTS), however, little is known about urinary microbiota correlations with clinicopathological parameters associated with BPH. Here, we investigate associations between the urinary microbiota and clinical parameters of patients with BPH undergoing surgery.

Methods: Forty-one patients with BPH undergoing surgery were recruited from two medical centers.

The Clinical and Molecular Profile of Lung Cancer Patients Harboring the R337H Germline Variant in a Brazilian Cancer Center: The Possible Mechanism of Carcinogenesis.

In southern and southeastern Brazil, the founder variant c.1010G>A (R337H) has been previously documented with a prevalence of 0.3% within the general population and linked to a heightened incidence of lung adenocarcinomas (LUADs).

Suspected Germline TP53 Variants and Clonal Hematopoiesis of Indeterminate Potential: Lessons Learned From a Molecular Tumor Board.

Objective: Li-Fraumeni syndrome (LFS) is a pan-cancer predisposition syndrome caused by germline pathogenic variants in the gene TP53. The interpretation of TP53 variants in clinical scenarios outside the classic LFS criteria may be challenging. Here, we report a patient affected by 2 primary cancers at later ages, who harbored a likely pathogenic TP53 at low allele frequency detected in a blood sample.

Set7 deletion attenuates isoproterenol-induced cardiac fibrosis and delays cardiac dysfunction.

Cardiovascular diseases are the main cause of death worldwide. Recent studies have revealed the influence of histone-modifying enzymes in cardiac remodeling and heart dysfunction. The Set7 methyltransferase regulates the expression of several genes through the methylation of histones and modulates the activity of non-histone proteins.

Commensal oral microbiota impacts ulcerative oral mucositis clinical course in allogeneic stem cell transplant recipients.

Oral mucositis (OM) is a complex acute cytotoxicity of antineoplastic treatment that affects 40-85% of patients undergoing hematopoietic stem-cell transplantation. OM is associated with prolonged hospitalization, increased extensive pharmacotherapy, need for parenteral nutrition, and elevated treatment costs. As OM onset relates to the mucosal microenvironment status, with a particular role for microbiota-driven inflammation, we aimed to investigate whether the oral mucosa microbiota was associated with the clinical course of OM in patients undergoing allogeneic hematopoietic stem-cell transplantation.

Choice of 16S Ribosomal RNA Primers Impacts Male Urinary Microbiota Profiling.

Accessibility to next-generation sequencing (NGS) technologies has enabled the profiling of microbial communities living in distinct habitats. 16S ribosomal RNA (rRNA) gene sequencing is widely used for microbiota profiling with NGS technologies. Since most used NGS platforms generate short reads, sequencing the full-length 16S rRNA gene is impractical.

Monoallelic deleterious MUTYH germline variants as a driver for tumorigenesis.

MUTYH encodes a glycosylase involved in the base excision repair of DNA. Biallelic pathogenic germline variants in MUTYH cause an autosomal recessive condition known as MUTYH-associated adenomatous polyposis and consequently increase the risk of colorectal cancer. However, reports of increased cancer risk in individuals carrying only one defective MUTYH allele are controversial and based on studies involving few individuals.

Disruption of the oral microbiota is associated with a higher risk of relapse after allogeneic hematopoietic stem cell transplantation.

Intestinal microbiota (IM) diversity and composition regulates host immunity and affects outcomes after allogeneic stem cell transplantation (allo-HSCT). We evaluated if the oral mucosa microbiota (OM) could impact the outcomes in patients who underwent allo-HSCT. Samples from the oral mucosa of 30 patients were collected at three time points: before the conditioning regimen, at aplasia, and at engraftment.

Dental Biofilm Microbiota Dysbiosis Is Associated With the Risk of Acute Graft--Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation.

Acute graft--host disease (aGVHD) is one of the major causes of death after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recently, aGVHD onset was linked to intestinal microbiota (IM) dysbiosis. However, other bacterial-rich gastrointestinal sites, such as the mouth, which hosts several distinctive microbiotas, may also impact the risk of GVHD.

Evidence of Cooperation between Hippo Pathway and Mutation in Thyroid Carcinomas.

Thyroid cancer incidences have been steadily increasing worldwide and are projected to become the fourth leading cancer diagnosis by 2030. Improved diagnosis and prognosis predictions for this type of cancer depend on understanding its genetic bases and disease biology. mutations have been found in a wide range of thyroid tumors, from benign to aggressive thyroid carcinomas.

Revealing the BRD4-NOTCH3 fusion: A novel hill in the cancer landscape.

Objectives: Gene fusions are becoming more evident in cancer scenario for either being the driver alterations, or for the great therapeutic target potential in many cases. Our aim was to characterize the BRD4-NOTCH3 fusion correlating with clinical features, and to determine the frequency of this fusion in the oncological population.

Material And Methods: One patient diagnosed with lung adenocarcinoma at Hospital Sírio-Libanês (Brazil) was included.

Deletion of miRNA-22 Induces Cardiac Hypertrophy in Females but Attenuates Obesogenic Diet-Mediated Metabolic Disorders.

Background/aims: Obesity is a risk factor associated with cardiometabolic complications. Recently, we reported that miRNA-22 deletion attenuated high-fat diet-induced adiposity and prevented dyslipidemia without affecting cardiac hypertrophy in male mice. In this study, we examined the impact of miRNA-22 in obesogenic diet-induced cardiovascular and metabolic disorders in females.

Metformin as an Alternative Radiosensitizing Agent to 5-Fluorouracil During Neoadjuvant Treatment for Rectal Cancer.

Background: Neoadjuvant chemoradiation for locally advanced rectal cancer combining 5-fluorouracil with radiation increases tumor regression compared with radiation alone. However, it occurs at the cost of significant treatment-related toxicity. Patients with rectal cancer using metformin have been associated with improved response to radiotherapy.

Gene expression changes associated with trajectories of psychopathology in a longitudinal cohort of children and adolescents.

We aimed to identify blood gene expression patterns associated to psychopathological trajectories retrieved from a large community, focusing on the emergence and remission of general psychiatric symptoms. Hundred and three individuals from the Brazilian High-Risk Cohort Study (BHRCS) for mental disorders were classified in four groups according to Child Behavior Checklist (CBCL) total score at the baseline (w0) and after 3 years (w1): low-high (L-H) (N = 27), high-low (H-L) (N = 12), high-high (H-H) (N = 34) and low-low (L-L) groups (N = 30). Blood gene expression profile was measured using Illumina HT-12 Beadchips, and paired analyses comparing w0 and w1 were performed for each group.

NDRG4 promoter hypermethylation is a mechanistic biomarker associated with metastatic progression in breast cancer patients.

The risk of developing metastatic disease in breast cancer patients is traditionally predictable based on the number of positive axillary lymph nodes, complemented with additional clinicopathological factors. However, since lymph node-negative patients have a 20-30% probability of developing metastatic disease, lymph node information alone is insufficient to accurately assess individual risk. Molecular approaches, such as multigene expression panels, analyze a set of cancer-related genes that more accurately predict the early risk of metastasis and the treatment response.

A straightforward assay to evaluate DNA integrity and optimize next-generation sequencing for clinical diagnosis in oncology.

Next generation sequencing (NGS) has become an informative tool to guide cancer treatment and conduce a personalized approach in oncology. The biopsy collected for pathologic analysis is usually stored as formalin-fixed paraffin-embedded (FFPE) blocks and then availed for molecular diagnostic, resulting in DNA molecules that are invariably fragmented and chemically modified. In an attempt to improve NGS based diagnostics in oncology we developed a straightforward DNA integrity assessment assay based on qPCR, defining clear parameters to whether NGS sequencing results is accurate or when it should be analyzed with caution.