Validation of ZIP4 as a tumour-associated antigen for nanotargeting.

Pancreatic ductal adenocarcinoma remains a highly aggressive and untreatable cancer. There is a need to develop a new PDAC-associated antigen-targeting drug delivery system to tackle this disease. We validated choosing ZIP4 as a putative target in PDAC theranostics.

Dynamic changes in immune cell populations by AXL kinase targeting diminish liver inflammation and fibrosis in experimental MASH.

Background And Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant health concern with limited treatment options. AXL, a receptor tyrosine kinase activated by the GAS6 ligand, promotes MASH through activation of hepatic stellate cells and inflammatory macrophages. This study identified cell subsets affected by MASH progression and the effect of AXL inhibition.

Scn1a haploinsufficiency in the prefrontal cortex leads to cognitive impairment and depressive phenotype.

Altered development and function of the prefrontal cortex (PFC) during adolescence is implicated in the origin of mental disorders. Deficits in the GABAergic system prominently contribute to these alterations. Nav1.

Prognostic Value of Soluble AXL in Serum from Heart Failure Patients with Preserved and Reduced Left Ventricular Ejection Fraction.

Heart failure (HF) is classified according to the degree of reduction in left ventricular ejection fraction (EF) in HF with reduced, mildly reduced, and preserved EF. Biomarkers could behave differently depending on EF type. Here, we analyze the soluble form of the AXL receptor tyrosine kinase (sAXL) in HF patients with reduced and preserved EF.

Long-term platinum-based drug accumulation in cancer-associated fibroblasts promotes colorectal cancer progression and resistance to therapy.

A substantial proportion of cancer patients do not benefit from platinum-based chemotherapy (CT) due to the emergence of drug resistance. Here, we apply elemental imaging to the mapping of CT biodistribution after therapy in residual colorectal cancer and achieve a comprehensive analysis of the genetic program induced by oxaliplatin-based CT in the tumor microenvironment. We show that oxaliplatin is largely retained by cancer-associated fibroblasts (CAFs) long time after the treatment ceased.

Sialyltransferase Inhibitor Ac3FNeu5Ac Reverts the Malignant Phenotype of Pancreatic Cancer Cells, and Reduces Tumor Volume and Favors T-Cell Infiltrates in Mice.

Hypersialylation is a feature of pancreatic ductal adenocarcinoma (PDA) and it has been related to tumor malignancy and immune suppression. In this work, we have evaluated the potential of the sialyltransferase inhibitor, Ac3FNeu5Ac, to decrease tumor sialoglycans in PDA and to revert its malignant phenotype. Sialoglycans on PDA cells were evaluated by flow cytometry, and the functional impact of Ac3FNeu5Ac was assessed using E-selectin adhesion, migration, and invasion assays.

Exploring the Role of Galectins in Cancer : In Vitro and In Vivo Approaches.

Galectins have been linked to tumorigenesis since 1975, even before this family of proteins was given its name. Since then, hundreds of papers have analyzed the role of different galectins in cancer development and progression, deciphering their involvement in many different pathological events, from the regulation of cell cycle, to angiogenesis, metastasis, and immune attack evasion. Importantly, the tumor galectin profile is often altered in many cancers and aberrant levels of some of the members of this family have been considered in diagnosis and frequently correlated with patient prognosis and clinicopathological characteristics.

Distinct roles for PARP-1 and PARP-2 in c-Myc-driven B-cell lymphoma in mice.

Dysregulation of the c-Myc oncogene occurs in a wide variety of hematologic malignancies, and its overexpression has been linked with aggressive tumor progression. Here, we show that poly (ADP-ribose) polymerase 1 (PARP-1) and PARP-2 exert opposing influences on progression of c-Myc-driven B-cell lymphoma. PARP-1 and PARP-2 catalyze the synthesis and transfer of ADP-ribose units onto amino acid residues of acceptor proteins in response to DNA strand breaks, playing a central role in the response to DNA damage.

Knockdown of α2,3-Sialyltransferases Impairs Pancreatic Cancer Cell Migration, Invasion and E-selectin-Dependent Adhesion.

Aberrant sialylation is frequently found in pancreatic ductal adenocarcinoma (PDA). α2,3-Sialyltransferases (α2,3-STs) ST3GAL3 and ST3GAL4 are overexpressed in PDA tissues and are responsible for increased biosynthesis of sialyl-Lewis (sLe) antigens, which play an important role in metastasis. This study addresses the effect of α2,3-STs knockdown on the migratory and invasive phenotype of PDA cells, and on E-selectin-dependent adhesion.

Impact of Galectins in Resistance to Anticancer Therapies.

Galectins are an endogenous family of β-galactoside-binding proteins that play complex and multifaceted roles at various stages of cancer progression, including modulation of tumor cell proliferation, signaling, adhesion, migration, invasion, epithelial-mesenchymal transition, angiogenesis, and immune escape. Recently, galectins have been implicated as major therapeutic determinants that confer sensitivity or resistance to a wide range of anticancer modalities including chemotherapy, radiotherapy, targeted therapies, antiangiogenic therapies, and immunotherapies. Here, we present an integrated approach to the pleiotropic functions of galectins and discuss their emerging roles with respect to mechanisms of resistance or sensitivity to anticancer therapies.

Galectins in the Tumor Microenvironment: Focus on Galectin-1.

In the last decades, the focus of cancer research has moved from epithelial cells to the tumor milieu, in an effort to better understand tumor development and progression, and with the important end goal of translating this knowledge into effective therapies. The galectin family of glycan-binding proteins displays important functions in cancer development and progression. Numerous groups have made outstanding contributions to deepen our knowledge about the role of galectins in the tumor-stroma crosstalk, defining them as key players in modulating interactions between tumor cells and the extracellular matrix, fibroblasts, endothelium, and the immune system.

The Galectin Family as Molecular Targets: Hopes for Defeating Pancreatic Cancer.

Galectins are a family of proteins that bind β-galactose residues through a highly conserved carbohydrate recognition domain. They regulate several important biological functions, including cell proliferation, adhesion, migration, and invasion, and play critical roles during embryonic development and cell differentiation. In adults, different galectin members are expressed depending on the tissue type and can be altered during pathological processes.

Galectins in prostate and bladder cancer: tumorigenic roles and clinical opportunities.

Advanced prostate and bladder cancer are two outstanding unmet medical needs for urological oncologists. The high prevalence of these tumours, lack of effective biomarkers and limited effective treatment options highlight the importance of basic research in these diseases. Galectins are a family of β-galactoside-binding proteins that are frequently altered (upregulated or downregulated) in a wide range of tumours and have roles in different stages of tumour development and progression, including immune evasion.

Modelling physical resilience in ageing mice.

Geroprotectors, a class of drugs targeting multiple deficits occurring with age, necessitate the development of new animal models to test their efficacy. The COST Action MouseAGE is a European network whose aim is to reach consensus on the translational path required for geroprotectors, interventions targeting the biology of ageing. In our previous work we identified frailty and loss of resilience as a potential target for geroprotectors.

Increased plasma levels of galectin-1 in pancreatic cancer: potential use as biomarker.

Pancreatic ductal adenocarcinoma (PDA) is the most frequent type of pancreatic cancer and one of the deadliest diseases overall. New biomarkers are urgently needed to allow early diagnosis, one of the only factors that currently improves prognosis. Here we analyzed whether the detection of circulating galectin-1 (Gal-1), a soluble carbohydrate-binding protein overexpressed in PDA tissue samples, can be used as a biomarker for PDA.

Interplay between epicardial adipose tissue, metabolic and cardiovascular diseases.

Cardiovascular disease is the primary cause of death in obese and diabetic patients. In these groups of patients, the alterations of epicardial adipose tissue (EAT) contribute to both vascular and myocardial dysfunction. Therefore, it is of clinical interest to determine the mechanisms by which EAT influences cardiovascular disease.

Immune Evasion in Pancreatic Cancer: From Mechanisms to Therapy.

Pancreatic ductal adenocarcinoma (PDA), the most frequent type of pancreatic cancer, remains one of the most challenging problems for the biomedical and clinical fields, with abysmal survival rates and poor therapy efficiency. Desmoplasia, which is abundant in PDA, can be blamed for much of the mechanisms behind poor drug performance, as it is the main source of the cytokines and chemokines that orchestrate rapid and silent tumor progression to allow tumor cells to be isolated into an extensive fibrotic reaction, which results in inefficient drug delivery. However, since immunotherapy was proclaimed as the breakthrough of the year in 2013, the focus on the stroma of pancreatic cancer has interestingly moved from activated fibroblasts to the immune compartment, trying to understand the immunosuppressive factors that play a part in the strong immune evasion that characterizes PDA.

Circulating CCL20 as a New Biomarker of Abdominal Aortic Aneurysm.

Autoimmunity appears to play a role in abdominal aortic aneurysm (AAA) pathology. Although the chemokine CCL20 has been involved in autoimmune diseases, its relationship with the pathogenesis of AAA is unclear. We investigated CCL20 expression in AAA and evaluated it as a potential biomarker for AAA.