PARP1 Characterization as a Potential Biomarker for p190+ Acute Lymphoblastic Leukemia.

Detection of t(9;22), and consequent fusion, is still a marker of worse prognosis for acute lymphoblastic leukemia (ALL), with resistance to tyrosine-kinase inhibitor therapy being a major obstacle in the clinical practice for this subset of patients. In this study, we investigated the effectiveness of targeting poly-ADP-ribose polymerase (PARP) in a model of p190+ ALL, the most common isoform to afflict ALL patients, and demonstrated the use of experimental PARP inhibitor (PARPi), AZD2461, as a therapeutic option with cytotoxic capabilities similar to that of imatinib, the current gold standard in medical care. We characterized cytostatic profiles, induced cell death, and biomarker expression modulation utilizing cell models, also providing a comprehensive genome-wide analysis through an aCGH of the model used, and further validated PARP1 differential expression in samples of ALL p190+ patients from local healthcare institutions, as well as in larger cohorts of online and readily available datasets.

Anticancer Potential of Flavonoids: An Overview with an Emphasis on Tangeretin.

Natural compounds with pharmacological activity, flavonoids have been the subject of an exponential increase in studies in the field of scientific research focused on therapeutic purposes due to their bioactive properties, such as antioxidant, anti-inflammatory, anti-aging, antibacterial, antiviral, neuroprotective, radioprotective, and antitumor activities. The biological potential of flavonoids, added to their bioavailability, cost-effectiveness, and minimal side effects, direct them as promising cytotoxic anticancer compounds in the optimization of therapies and the search for new drugs in the treatment of cancer, since some extensively antineoplastic therapeutic approaches have become less effective due to tumor resistance to drugs commonly used in chemotherapy. In this review, we emphasize the antitumor properties of tangeretin, a flavonoid found in citrus fruits that has shown activity against some hallmarks of cancer in several types of cancerous cell lines, such as antiproliferative, apoptotic, anti-inflammatory, anti-metastatic, anti-angiogenic, antioxidant, regulatory expression of tumor-suppressor genes, and epigenetic modulation.

Mature tertiary lymphoid structures are key niches of tumour-specific immune responses in pancreatic ductal adenocarcinomas.

Objective: To better understand the immune microenvironment of pancreatic ductal adenocarcinomas (PDACs), here we explored the relevance of T and B cell compartmentalisation into tertiary lymphoid structures (TLSs) for the generation of local antitumour immunity.

Design: We characterised the functional states and spatial organisation of PDAC-infiltrating T and B cells using single-cell RNA sequencing (scRNA-seq), flow cytometry, multicolour immunofluorescence, gene expression profiling of microdissected TLSs, as well as in vitro assays. In addition, we performed a pan-cancer analysis of tumour-infiltrating T cells using scRNA-seq and sc T cell receptor sequencing datasets from eight cancer types.

One binge-type cycle of alcohol plus ketamine exposure induces emotional-like disorders associated with oxidative damage in adolescent female rats.

Drug abuse is a global public health problem among adolescents, with alcohol often used in association with other psychotropic drugs, such as ketamine. Considering the scarcity of evidence, this study aimed to investigate emotional behavioral effects induced by ethanol plus ketamine co-abuse, as well as oxidative biochemistry, and neurotrophic mediator in the prefrontal cortex and hippocampus in the early withdrawal of adolescent female rats. Animals were divided into control, ethanol, ketamine, and ethanol plus ketamine groups.

Repeated Cycles of Binge-Like Ethanol Exposure Induces Neurobehavioral Changes During Short- and Long-Term Withdrawal in Adolescent Female Rats.

Alcohol consumption is spread worldwide and can lead to an abuse profile associated with severe health problems. Adolescents are more susceptible to addiction and usually consume ethanol in a binge drinking pattern. This form of consumption can lead to cognitive and emotional disorders, however scarce studies have focused on long-term hazardous effects following withdrawal periods after binge drinking in adolescents.

Expression of Is Epigenetically Regulated by DNA Methylation and Correlates with Immune Infiltrates in Clear-Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (KIRC) is the most common and highly malignant pathological type of kidney cancer, characterized by a profound metabolism dysregulation. As part of aspartate biosynthesis, mitochondrial (glutamic-oxaloacetic transaminase 2) is essential for regulating cellular energy production and biosynthesis, linking multiple pathways. Nevertheless, the expression profile and prognostic significance of in KIRC remain unclear.

Antiviral Responses in Cancer: Boosting Antitumor Immunity Through Activation of Interferon Pathway in the Tumor Microenvironment.

In recent years, it became apparent that cancers either associated with viral infections or aberrantly expressing endogenous retroviral elements (EREs) are more immunogenic, exhibiting an intense intra-tumor immune cell infiltration characterized by a robust cytolytic apparatus. On the other hand, epigenetic regulation of EREs is crucial to maintain steady-state conditions and cell homeostasis. In line with this, epigenetic disruptions within steady-state cells can lead to cancer development and trigger the release of EREs into the cytoplasmic compartment.

B Cell Orchestration of Anti-tumor Immune Responses: A Matter of Cell Localization and Communication.

The immune system plays a crucial role in cancer development either by fostering tumor growth or destroying tumor cells, which has open new avenues for cancer immunotherapy. It was only over the last decade that the role of B cells in controlling anti-tumor immune responses in the tumor milieu has begun to be appreciated. B and plasma cells can exert anti-tumor effects through antibody-dependent cell cytotoxicity (ADCC) and activation of the complement cascade, even though their effector functions extend beyond the classical humoral immunity.

Meningiomas: An Overview of the Landscape of Copy Number Alterations in Samples from an Admixed Population.

Meningiomas are considered the most common intracranial tumors, affecting mainly women. Studies in mixed populations can be of great importance to clarify issues related to the genetic diversity of tumors and their development. Considering that data obtained from analyses of the profile of copy number alterations (CNA) have been a useful diagnostic indicator for many types of tumors and that meningiomas show a complex pattern of gains and losses in the number of copies, our objective was to analyze the CNA profile in 33 samples of meningiomas of different histological grades (WHO Grade I-III) from patients in a city located in the Amazon region of Brazil, using aCGH.

Pisosterol Induces G2/M Cell Cycle Arrest and Apoptosis via the ATM/ATR Signaling Pathway in Human Glioma Cells.

Background: Pisosterol, a triterpene derived from Pisolithus tinctorius, exhibits potential antitumor activity in various malignancies. However, the molecular mechanisms that mediate the pisosterol-specific effects on glioma cells remain unknown.

Objective: This study aimed to evaluate the antitumoral effects of pisosterol on glioma cell lines.

Detection and Correlation of Single and Concomitant , and Alterations in Gliomas.

Gliomas are the most frequent primary tumors of central nervous system and represent a heterogeneous group of tumors that originates from the glial cells. , , and are important tumor suppressor genes that encode proteins involved in sustaining cellular homeostasis by different signaling pathways. Though genetic alterations in these genes play a significant role in tumorigenesis, few studies are available regarding the incidence and relation of concomitant , , and alterations in gliomas.

An update on the epigenetics of glioblastomas.

Glioblastomas, also known as glioblastoma multiforme (GBM), are the most aggressive and malignant type of primary brain tumor in adults, exhibiting notable variability at the histopathological, genetic and epigenetic levels. Recently, epigenetic alterations have emerged as a common hallmark of many tumors, including GBM. Considering that a deeper understanding of the epigenetic modifications that occur in GBM may increase the knowledge regarding the tumorigenesis, progression and recurrence of this disease, in this review we discuss the recent major advances in GBM epigenetics research involving histone modification, glioblastoma stem cells, DNA methylation, noncoding RNAs expression, including their main alterations and the use of epigenetic therapy as a valid option for GBM treatment.

Genotyping and prevalence of Chlamydia trachomatis infection among women in Belém, Pará, northern Brazil.

Introduction: Genital Chlamydia trachomatis infection is one of the most prevalent sexually transmitted diseases in women, and undetected cases of the disease are highly associated with long-term complications. Despite the high prevalence of infections in Brazil, very little is known about the distribution of C. trachomatis genovars.

Expression Analysis of Genes Involved in the RB/E2F Pathway in Astrocytic Tumors.

Astrocytic gliomas, which are derived from glial cells, are considered the most common primary neoplasias of the central nervous system (CNS) and are histologically classified as low grade (I and II) or high grade (III and IV). Recent studies have shown that astrocytoma formation is the result of the deregulation of several pathways, including the RB/E2F pathway, which is commonly deregulated in various human cancers via genetic or epigenetic mechanisms. On the basis of the assumption that the study of the mechanisms controlling the INK4/ARF locus can help elucidate the molecular pathogenesis of astrocytic tumors, identify diagnostic and prognostic markers, and help select appropriate clinical treatments, the present study aimed to evaluate and compare methylation patterns using bisulfite sequencing PCR and evaluate the gene expression profile using real-time PCR in the genes CDKN2A, CDKN2B, CDC6, Bmi-1, CCND1, and RB1 in astrocytic tumors.

Morphology and mitochondrial phylogenetics reveal that the Amazon River separates two eastern squirrel monkey species: Saimiri sciureus and S. collinsi.

Saimiri has a complicated taxonomic history, and there is continuing disagreement about the number of valid taxa. Despite these controversies, one point of consensus among morphologists has been that the eastern Amazonian populations of squirrel monkeys form a single terminal taxon, Saimiri sciureus sciureus (Linnaeus, 1758). This group is distributed to both the north and south of the middle to lower Amazon River and in the Marajó Archipelago.

Perspectives on new biomarkers in gastric cancer: diagnostic and prognostic applications.

Gastric cancer is considered one of the most deadly tumors worldwide. Even with the decline in its incidence, the mortality rate of this disease has remained high, mainly due to its late diagnosis and to the lack of precise prognostic markers. The main purpose of this review is to present genetic, epigenetic and proteomic molecular markers that may be used in a diagnostic and prognostic manner and to discuss the pros and cons of each type of marker for improving clinical practice.

Phylogeography of the dark fruit-eating bat Artibeus obscurus in the Brazilian Amazon.

Artibeus obscurus (Mammalia: Chiroptera) is endemic to South America, being found in at least 18 Brazilian states. Recent studies revealed that different populations of this genus present distinct phylogeographic patterns; however, very little is known on the population genetics structure of A. obscurus in the Amazon rainforest.