Evaluation of the Anti-Cancer Potential of Extracellular Vesicles Derived from Human Amniotic Fluid Stem Cells: Focus on Effective miRNAs in the Treatment of Melanoma Progression.

Mesenchymal stromal cells (MSCs) and their secretome show intrinsic antitumor properties, however, the anti-cancer effects of MSCs remain debated and depend on the cancer type or model. MSCs derived from discarded samples, such as human amniotic fluid (hAFSC), have been introduced as an attractive and potent stem cell source for clinical applications due to their collection procedures, which minimize ethical issues. Until now, various studies have obtained controversial results and poor understanding of the mechanisms behind the effects of perinatal cells on cancer cells.

Signaling pathways and bone marrow microenvironment in myelodysplastic neoplasms.

Key signaling pathways within the Bone Marrow Microenvironment (BMM), such as Notch, Phosphoinositide-Specific Phospholipase C (PI-PLCs), Transforming Growth Factor β (TGF-β), and Nuclear Factor Kappa B (NF-κB), play a vital role in the progression of Myelodysplastic Neoplasms (MDS). Among the various BMM cell types, Mesenchymal Stromal Cells (MSCs) are particularly central to these pathways. While these signaling routes can independently affect both MSCs and Hematopoietic Stem Cells (HSCs), they most importantly alter the dynamics of their interactions, leading to abnormal changes in survival, differentiation, and quiescence.

Myoblast-Derived Galectin 3 Impairs the Early Phases of Osteogenesis Affecting Notch and Akt Activity.

Galectin-3 (Gal-3) is a pleiotropic lectin produced by most cell types, which regulates multiple cellular processes in various tissues. In bone, depending on its cellular localization, Gal-3 has a dual and opposite role. If, on the one hand, intracellular Gal-3 promotes bone formation, on the other, its circulating form affects bone remodeling, antagonizing osteoblast differentiation and increasing osteoclast activity.

The potential of the nutraceutical berberine in the treatment of hepatocellular carcinoma and other liver diseases such as NAFLD and NASH.

Hepatocellular carcinoma (HCC) is a common cancer which unfortunately has poor outcomes. Common anti-cancer treatments such as chemotherapy and targeted therapy have not increased patient survival significantly. A common treatment for HCC patients is transplantation, however, it has limitations and complications.

Nuclear Phospholipids and Signaling: An Update of the Story.

In the last three decades, the presence of phospholipids in the nucleus has been shown and thoroughly investigated. A considerable amount of interest has been raised about nuclear inositol lipids, mainly because of their role in signaling acting. Here, we review the main issues of nuclear phospholipid localization and the role of nuclear inositol lipids and their related enzymes in cellular signaling, both in physiological and pathological conditions.

Detection of Cancer Stem Cells in Normal and Dysplastic/Leukemic Human Blood.

The hierarchical organization of the leukemic stem cells (LSCs) is identical to that of healthy counterpart cells. It may be split into roughly three stages: a small number of pluripotent stem cells at the top, few lineage-restricted cells in the middle, and several terminally differentiated blood cells at the bottom. Although LSCs can differentiate into the hematopoietic lineage, they can also accumulate as immature progenitor cells, also known as blast cells.

Deciphering signaling pathways in hematopoietic stem cells: the molecular complexity of Myelodysplastic Syndromes (MDS) and leukemic progression.

Myelodysplastic Syndromes, a heterogeneous group of hematological disorders, are characterized by abnormalities in phosphoinositide-dependent signaling, epigenetic regulators, apoptosis, and cytokine interactions within the bone marrow microenvironment, contributing to disease pathogenesis and neoplastic growth. Comprehensive knowledge of these pathways is crucial for the development of innovative therapies that aim to restore normal apoptosis and improve patient outcomes.

Nuclear Phosphoinositides as Key Determinants of Nuclear Functions.

Polyphosphoinositides (PPIns) are signalling messengers representing less than five per cent of the total phospholipid concentration within the cell. Despite their low concentration, these lipids are critical regulators of various cellular processes, including cell cycle, differentiation, gene transcription, apoptosis and motility. PPIns are generated by the phosphorylation of the inositol head group of phosphatidylinositol (PtdIns).

A miRNA screening identifies miR-192-5p as associated with response to azacitidine and lenalidomide therapy in myelodysplastic syndromes.

Background: miRNAs are small non-coding RNAs that regulate gene expression and are linked to cancer development and progression. miRNA profiles are currently studied as new prognostic factors or therapeutic perspectives. Among hematological cancers, myelodysplastic syndromes at higher risk of evolution into acute myeloid leukemia are treated with hypomethylating agents, like azacitidine, alone or in combination with other drugs, such as lenalidomide.

Effects of chloroquine and hydroxychloroquine on the sensitivity of pancreatic cancer cells to targeted therapies.

Approaches to improve pancreatic cancer therapy are essential as this disease has a very bleak outcome. Approximately 80% of pancreatic cancers are pancreatic ductal adenocarcinomas (PDAC). PDAC is a cancer which is difficult to effectively treat as it is often detected late in the disease process.

Effects of TP53 Mutations and miRs on Immune Responses in the Tumor Microenvironment Important in Pancreatic Cancer Progression.

Approximately 90% of pancreatic cancers are pancreatic ductal adenocarcinomas (PDAC). PDAC is the fourth leading cause of cancer death world-wide. Therapies for PDAC are largely ineffective due to the dense desmoplastic tumor microenvironment which prevents chemotherapeutic drugs and small molecule inhibitors from exerting effective anti-cancer effects.

Molecular International Prognostic Scoring System for Myelodysplastic Syndromes.

BACKGROUND: Risk stratification and therapeutic decision-making for myelodysplastic syndromes (MDS) are based on the International Prognostic Scoring System–Revised (IPSS-R), which considers hematologic parameters and cytogenetic abnormalities. Somatic gene mutations are not yet used in the risk stratification of patients with MDS. METHODS: To develop a clinical-molecular prognostic model (IPSS-Molecular [IPSS-M]), pretreatment diagnostic or peridiagnostic samples from 2957 patients with MDS were profiled for mutations in 152 genes.

Microbiota-Gut-Brain Axis in Neurological Disorders: From Leaky Barriers Microanatomical Changes to Biochemical Processes.

Background: The gastrointestinal tract and the central nervous system are distinct because of evident morpho-functional features. Nonetheless, evidence indicates that these systems are bidirectionally connected through the gut-brain axis, defined as the signaling that takes place between the gastrointestinal tract and central nervous system, which plays in concert with the gut microbiota, i.e.

Effects of the Mutant TP53 Reactivator APR-246 on Therapeutic Sensitivity of Pancreatic Cancer Cells in the Presence and Absence of WT-TP53.

The TP53 tumor suppressor is mutated in ~75% of pancreatic cancers. The mutant TP53 protein in pancreatic ductal adenocarcinomas (PDAC) promotes tumor growth and metastasis. Attempts have been made to develop molecules that restore at least some of the properties of wild-type (WT) TP53.

Effects of the MDM2 inhibitor Nutlin-3a on sensitivity of pancreatic cancer cells to berberine and modified berberines in the presence and absence of WT-TP53.

Approaches to improve pancreatic cancer therapy are essential as this disease has a very bleak outcome. Approximately 80% of pancreatic cancers are pancreatic ductal adenocarcinomas (PDAC). A key regulatory gene frequently mutated (∼75%) in PDAC is the TP53 tumor suppressor gene which controls the transcription of multiple genes involved in cell cycle progression, apoptosis, cancer progression and other growth regulatory processes.

Role of PLCγ1 in the modulation of cell migration and cell invasion in glioblastoma.

Phosphoinositide-specific phospholipases C (PLCs) are a class of enzymes involved in several cell activities, such as cell cycle regulation, proliferation, differentiation and cytoskeletal dynamics. Among these enzymes, PLCγ1 is one of the most expressed PLCs in the brain, contributing to a complex network in the developing nervous system. Several studies have shown that PLCγ1 signaling imbalance is linked to several brain disorders, including glioblastoma, the most aggressive brain tumor in adults.

"Modulating Phosphoinositide Profiles as a Roadmap for Treatment in Acute Myeloid Leukemia".

Polyphosphoinositides (PPIns) and their modulating enzymes are involved in regulating many important cellular functions including proliferation, differentiation or gene expression, and their deregulation is involved in human diseases such as metabolic syndromes, neurodegenerative disorders and cancer, including Acute Myeloid Leukemia (AML). Given that PPIns regulating enzymes are highly druggable targets, several studies have recently highlighted the potential of targeting them in AML. For instance many inhibitors targeting the PI3K pathway are in various stages of clinical development and more recently other novel enzymes such as PIP4K2A have been implicated as AML targets.