Cohesin Gene Promoter Methylation in Patients with Acute Myeloid Leukemia.

Background: Aberrant gene promoter methylation is one of the hallmarks of Acute Myeloid Leukemia (AML). is an important gene, implicated in sister chromatids cohesion, DNA repair, the regulation of gene transcription, apoptosis and hematopoiesis.

Methods: In this study, we investigate the possible implication of promoter methylation in AML pathogenesis using a cohort of AML patients and a cohort of healthy individuals.

Exploration of isatin-based inhibitors of SARS-CoV-2 Nsp15 endoribonuclease.

The global health crisis caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) urges the development of new antiviral agents with broad coronavirus coverage. Due to its key role in viral evasion from the host innate immune response, the coronavirus Nsp15 uridine-specific endoribonuclease (EndoU) is of high interest as a drug target. Considering that the isatin scaffold is well-known for its versatile pharmacological properties, we synthesized and evaluated a series of compounds carrying an isatin core.

Development of a novel apigenin prodrug programmed for alkaline-phosphatase instructed self-inhibition to combat cancer.

Elevated levels of alkaline phosphatase (ALP) in the tumor microenvironment (TME) are a hallmark of cancer progression and thus inhibition of ALP could serve as an effective approach against cancer. Herein, we developed a novel prodrug approach to tackle cancer that bears self-inhibiting alkaline phosphatase-responsiveness properties that can enhance at the same time the solubility of the parent compound. To probe this novel concept, we selected apigenin as the cytotoxic agent since we first unveiled, that it directly interacts and inhibits ALP activity.

Using Sister Chromatid Exchange Assay to Detect Homologous Recombination Deficiency in Epigenetically Deregulated Urothelial Carcinoma Cells.

Sister chromatid exchange (SCE) is the process of exchanging regions between two sister chromatids during DNA replication. Exchanges between replicated chromatids and their sisters can be visualized in cells when DNA synthesis in one chromatid is labelled by 5-bromo-2'-deoxyuridine (BrdU). Homologous recombination (HR) is considered as the principal mechanism responsible for the sister chromatid exchange (SCE) upon replication fork collapse, and therefore SCE frequency upon genotoxic conditions reflects the capacity of HR repair to respond to replication stress.

Cancer Evolution in Precision Medicine Era.

Recent advances in our understanding of cancer, driven mainly by the emergence of new technologies have highlighted that heterogeneity shapes not only the genetic profile of tumors but also their epigenetic and gene expression profile [...

Prognostic Significance of Methylation in Plasma Cell-Free DNA in Advanced High-Grade Serous Ovarian Cancer.

Background: Epigenetic alterations in ctDNA are highly promising as a source of novel potential liquid biopsy biomarkers and comprise a very promising liquid biopsy approach in ovarian cancer, for early diagnosis, prognosis and response to treatment.

Methods: In the present study, we examined the methylation status of six gene promoters (, , , , and in high-grade serous ovarian cancer (HGSOC). We evaluated the prognostic significance of DNA methylation of these six gene promoters in primary tumors (FFPEs) and plasma cfDNA samples from patients with early, advanced and metastatic HGSOC.

Biological and Clinical Significance of Adaptive Evolution of Coronaviruses.

RNA viral genomes are generally small genomes that rarely exceed 10 kb in size [...

N-terminal domain mutations of the spike protein are structurally implicated in epitope recognition in emerging SARS-CoV-2 strains.

During the past two years, the world has been ravaged by a global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Acquired mutations in the SARS-CoV-2 genome affecting virus infectivity and/or immunogenicity have led to a number of novel strains with higher transmissibility compared to the original Wuhan strain. Mutations in the receptor binding domain (RBD) of the SARS-CoV-2 spike protein have been extensively studied in this context.

Promoter Methylation in Plasma Cell-Free DNA in Prostate Cancer.

Liquid biopsy provides real-time monitoring of tumor evolution and response to therapy through analysis of circulating tumor cells (CTCs) and plasma-circulating tumor DNA (ctDNA). is a critical gene which plays an important role in cell proliferation; however, its accurate role in other cellular networks is under research. promoter methylation has been so far reported in colorectal neoplasia and metastatic breast cancer.

HDAC Inhibitors: Dissecting Mechanisms of Action to Counter Tumor Heterogeneity.

Intra-tumoral heterogeneity presents a major obstacle to cancer therapeutics, including conventional chemotherapy, immunotherapy, and targeted therapies. Stochastic events such as mutations, chromosomal aberrations, and epigenetic dysregulation, as well as micro-environmental selection pressures related to nutrient and oxygen availability, immune infiltration, and immunoediting processes can drive immense phenotypic variability in tumor cells. Here, we discuss how histone deacetylase inhibitors, a prominent class of epigenetic drugs, can be leveraged to counter tumor heterogeneity.

The Role of Coronavirus RNA-Processing Enzymes in Innate Immune Evasion.

Viral RNA sensing triggers innate antiviral responses in humans by stimulating signaling pathways that include crucial antiviral genes such as interferon. RNA viruses have evolved strategies to inhibit or escape these mechanisms. Coronaviruses use multiple enzymes to synthesize, modify, and process their genomic RNA and sub-genomic RNAs.

Animal Coronaviruses Induced Apoptosis.

Apoptosis is a form of programmed death that has also been observed in cells infected by several viruses. It is considered one of the most critical innate immune mechanisms that limits pathogen proliferation and propagation before the initiation of the adaptive immune response. Recent studies investigating the cellular responses to SARS-CoV and SARS-CoV-2 infection have revealed that coronaviruses can alter cellular homeostasis and promote cell death, providing evidence that the modulation of apoptotic pathways is important for viral replication and propagation.

Exploring the Eco-Evolutionary Dynamics of Tumor Subclones.

Mutational processes constantly shape the cancer genome and defects in DNA repair pathways of tumor cells facilitate the accumulation of genomic alterations [...

Monitoring of Active Notch Signaling in Mouse Bladder Urothelium.

Notch signaling plays a crucial role in differentiation and homeostasis in a wide variety of epithelia. The tumor suppressor role of Notch in bladder urothelium is well accepted as the inactivation of this pathway due to damaging mutations in its components is associated with neoplastic transformation. Monitoring Notch signaling is therefore critical to understand how the deregulation of cell-cell communication can lead to differentiation loss and carcinogenesis.

Mitonuclear Interactions in the Maintenance of Mitochondrial Integrity.

In eukaryotic cells, mitochondria originated in an α-proteobacterial endosymbiont. Although these organelles harbor their own genome, the large majority of genes, originally encoded in the endosymbiont, were either lost or transferred to the nucleus. As a consequence, mitochondria have become semi-autonomous and most of their processes require the import of nuclear-encoded components to be functional.

TP53 mutational landscape of metastatic head and neck cancer reveals patterns of mutation selection.

Background: Head and neck squamous cell carcinoma is a heterogeneous disease with respect to the anatomic site of the primary tumor. On the other hand, it is highly recurrent, and once metastatic, it is associated with poor prognosis. TP53 is the most commonly mutated gene in primary disease.

Resolving DNA Damage: Epigenetic Regulation of DNA Repair.

Epigenetic research has rapidly evolved into a dynamic field of genome biology. Chromatin regulation has been proved to be an essential aspect for all genomic processes, including DNA repair. Chromatin structure is modified by enzymes and factors that deposit, erase, and interact with epigenetic marks such as DNA and histone modifications, as well as by complexes that remodel nucleosomes.

Targeting DNA repair in cancer: current state and novel approaches.

DNA damage response, DNA repair and genomic instability have been under study for their role in tumor initiation and progression for many years now. More recently, next-generation sequencing on cancer tissue from various patient cohorts have revealed mutations and epigenetic silencing of various genes encoding proteins with roles in these processes. These findings, together with the unequivocal role of DNA repair in therapeutic response, have fueled efforts toward the clinical exploitation of research findings.

Unraveling UCA1 lncRNA prognostic utility in urothelial bladder cancer.

In the era of precision oncology, bladder cancer (BlCa) is characterized by generic patient management and lack of personalized prognosis and surveillance. Herein, we have studied the clinical significance of urothelial cancer associated 1 (UCA1) lncRNA in improving patients' risk stratification and prognosis. A screening cohort of 176 BlCa patients was used for UCA1 quantification.

The lysine-specific methyltransferase KMT2C/MLL3 regulates DNA repair components in cancer.

Genome-wide studies in tumor cells have indicated that chromatin-modifying proteins are commonly mutated in human cancers. The lysine-specific methyltransferase 2C (KMT2C/MLL3) is a putative tumor suppressor in several epithelia and in myeloid cells. Here, we show that downregulation of KMT2C in bladder cancer cells leads to extensive changes in the epigenetic status and the expression of DNA damage response and DNA repair genes.

A new tumor suppressor role for the Notch pathway in bladder cancer.

The Notch signaling pathway controls cell fates through interactions between neighboring cells by positively or negatively affecting the processes of proliferation, differentiation and apoptosis in a context-dependent manner. This pathway has been implicated in human cancer as both an oncogene and a tumor suppressor. Here we report new inactivating mutations in Notch pathway components in over 40% of human bladder cancers examined.

Markers of epithelial to mesenchymal transition in association with survival in head and neck squamous cell carcinoma (HNSCC).

Background: Elucidating the molecular phenotype of cancers with high metastatic potential will facilitate the development of novel therapeutic approaches to the disease. Gene expression profiles link epithelial to mesenchymal transition (EMT) phenotype with high-risk HNSCC. We sought to determine the role of protein biomarkers of EMT in head and neck squamous carcinoma (HNSC) prognosis.