Systemic chemotherapy for patients with advanced and metastatic bladder cancer: current status and future directions

n/

The role of Micro-RNAs in Hepatocellular Carcinoma: From Molecular Biology to Treatment

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third leading cause of cancer deaths. microRNAs (miRNAs) are evolutionary conserved small non-coding RNA that negatively regulate gene expression and protein translation. Recent evidences have shown that they are involved in many biological processes, from development and cell-cycle regulation to apoptosis. miRNAs can behave as tumor suppressor or promoter of oncogenesis depending on the cellular function of their targets. Moreover, they are frequently dysregulated in HCC. In this review we summarize the latest findings of miRNAs regulation in HCC and their role as potentially diagnostic and prognostic biomarkers for HCC. We highlight development of miRNAs as potential therapeutic targets for HCC

DEAD-Box Helicase 4 (Ddx4)+ Stem Cells Sustain Tumor Progression in Non-Serous Ovarian Cancers

DEAD-Box Helicase 4 (Ddx4)+ ovarian stem cells are able to differentiate into several cell types under appropriate stimuli. Ddx4 expression has been correlated with poor prognosis of serous ovarian cancer (OC), while the potential role of Ddx4+ cells in non-serous epithelial OC (NS-EOC) is almost unexplored. The aim of this study was to demonstrate the presence of Ddx4+ cells in NS-EOC and investigate the effect of follicle-stimulating hormone (FSH) on this population. Increased Ddx4 expression was demonstrated in samples from patients with advanced NS-EOC, compared to those with early-stage disease. Under FSH stimulation, OC-derived Ddx4+ cells differentiated into mesenchymal-like (ML) cells, able to deregulate genes involved in cell migration, invasiveness, stemness and chemoresistance in A2780 OC cells. This effect was primarily induced by ML-cells deriving from advanced NS-EOC, suggesting that a tumor-conditioned germ cell niche inhabits its microenvironment and is able to modulate, in a paracrine manner, tumor cell behavior through transcriptome modulation

Osteotropism of neuroendocrine tumors: role of the CXCL12/ CXCR4 pathway in promoting EMT in vitro.

Neuroendocrine tumors (NETs) metastasize to the skeleton in approximately 20% of patients. We have previously shown that the epithelial-mesenchymal transition (EMT) regulates the NET osteotropism and that CXCR4 overexpression predicts bone spreading. Here, we unravel the molecular mechanisms linking the activation of the CXCL12/CXCR4 axis to the bone colonization of NETs using cell lines representative of pancreatic (BON1, CM, QGP1), intestinal (CNDT 2.5), and bronchial origin (H727). By combining flow cytometry and ELISA, BON1, CM and QGP1 cells were defined as CXCR4high/CXCL12low, while H727 and CNDT 2.5 were CXCR4low/CXCL12high. CXCL12 was inert on cell proliferation, but significantly increased the in vitro osteotropism of CXCR4high/CXCL12low cells, as assessed by transwell assays with or without Matrigel membranes. In these cells, CXCL12 induced in vitro a marked EMT-like transcriptional shift with acquirement of a mesenchymal shape. The nuclei of CXCR4high/CXCL12low NET cells were typically enriched in non-phosphorylated CXCR4, particularly upon agonist stimulation. Silencing of CXCR4 via siRNA prevented the CXCL12-induced EMT in CXCR4high/CXCL12low NET cell lines resulting in the abrogation of both migration and transcriptional mesenchymal patterns. Our data suggest that CXCL12 conveys EMT-promoting signals in NET cells through CXCR4, which in turn regulates transcriptional, morphologic and functional modifications resulting in enhanced in vitro osteotropism of NET cells. Unique functions of CXCR4 may be segregated in relation to its subcellular localization and may acquire potential relevance in future in vivo studies

COVID-19 pandemic and the crisis of health systems: The experience of the apulia cancer network and of the comprehensive cancer center istituto tumori “Giovanni Paolo II” of bari

On 11 March 2020, the World Health Organization declared a new disease caused by a novel virus characterized by rapid human-to-human transmission and named severe acute respiratory syndrome coronoavirus-2 (SARS-CoV-2) a pandemic. In terms of this ongoing international scenario, we report the situation in Apulia, a region of southern Italy that, as of April 2, has not yet been overwhelmed by this health emergency. In particular, we consider the care models that have been adopted, especially those that manage the requests of cancer patients

NADH-cytochrome b5 reductase and cytochrome b5 isoforms as models for the study of post-translational targeting to the endoplasmic reticulum

AbstractCytochrome b5 and NADH-cytochrome b5, reductase are integral membrane proteins with cytosolic active domains and short membrane anchors, which are inserted post-translationally into their target membranes. Both are produced as different isoforms, with different localizations, in mammalian cells. In the rat, the reductase gene generates two transcripts by an alternative promoter mechanism: a ubiquitous mRNA coding for the myristylated membrane-bound form, and an erythroid mRNA which generates both the soluble form and a nonmyristylated membrane-binding form. The available evidence indicates that the ubiquitous myristylated form binds to the cytosolic face of both outer mitochondrial membranes and ER. In contrast, two genes code for two homologous forms of cytochrome b5, one of which is found on outer mitochondrial membranes, the other on the ER. The gene specifying the ER form probably also generates an erythroid-specific mRNA by alternative splicing, which codes for soluble cytochrome b5. Possible molecular mechanisms responsible for the observed localizations of these different enzyme isoforms are discussed

Cytokine Overproduction, T-Cell Activation, and Defective T-Regulatory Functions Promote Nephritis in Systemic Lupus Erythematosus

Lupus nephritis (LN) occurs in more than one-third of patients with systemic lupus erythematosus. Its pathogenesis is mostly attributable to the glomerular deposition of immune complexes and overproduction of T helper- (Th-) 1 cytokines. In this context, the high glomerular expression of IL-12 and IL-18 exerts a major pathogenetic role. These cytokines are locally produced by both macrophages and dendritic cells (DCs) which attract other inflammatory cells leading to maintenance of the kidney inflammation. However, other populations including T-cells and B-cells are integral for the development and worsening of renal damage. T-cells include many pathogenetic subsets, and the activation of Th-17 in keeping with defective T-regulatory (Treg) cell function regards as further event contributing to the glomerular damage. These populations also activate B-cells to produce nephritogenic auto-antibodies. Thus, LN includes a complex pathogenetic mechanism that involves different players and the evaluation of their activity may provide an effective tool for monitoring the onset of the disease