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Topic Review
Glycosylation of Cancer Extracellular Vesicles
Glycans are major constituents of extracellular vesicles (EVs). Alterations in the glycosylation pathway are a common feature of cancer cells, which gives rise to de novo or increased synthesis of particular glycans. Therefore, glycans and glycoproteins have been widely used in the clinic as both stratification and prognosis cancer biomarkers. Interestingly, several of the tumor-associated glycans have already been identified in cancer EVs, which constitutes valuable sources of cancer biomarkers. Furthermore, glycans have also shown to play a role in EV protein sorting, uptake and tropism. Altogether, the EV glycan signatures hold tremendous potential to be applied into the clinical setting for both biomarker discovery and as therapeutic delivery systems.
  • 1.1K
  • 25 Jan 2021
Topic Review
COVID-19 effect in Stem cells
The new strain of coronavirus (severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)) emerged in 2019 and hence is often referred to as coronavirus disease 2019 (COVID-19). This disease causes hypoxic respiratory failure and acute respiratory distress syn-drome (ARDS), and is considered as the cause of a global pandemic. Very limited reports in addi-tion to ex vivo model systems are available to understand the mechanism of action of this virus, which can be used for testing of any drug efficacy against virus infectivity. COVID-19 induces tissue stem cell loss, resulting inhibition of epithelial repair followed by inflammatory fibrotic con-sequences. Development of clinically relevant models is important to examine the impact of the COVID-19 virus in tissue stem cells among different organs.
  • 513
  • 22 Jan 2021
Topic Review
Fascin
Fascin, an actin-binding protein, regulates many developmental migrations and contributes to cancer metastasis.
  • 804
  • 21 Jan 2021
Topic Review
Treatment of Intrahepatic Cholangiocarcinoma
Liver metastases are a major management problem; since they occur in tumors of different origin, they are often multiple, difficult to visualize and can lie dormant for many years. Patients with liver metastases usually die of their disease, mostly due to liver failure, since systemic treatments are unable to eradicate micro-metastasis, and interventional loco-regional procedures cannot treat all existing ones. Cholangiocarcinoma (CCA) is the second most common primary liver tumor, showing a poor overall prognosis. When resection is not possible, treatment options include tumor-focused or local ablative therapy, organ-focused or regional therapy and systemic therapy. We reviewed available loco-regional therapeutic options, with particular focus on the CHEMOSAT® Melphalan/Hepatic Delivery System (CS-HDS), which is uniquely positioned to perform a percutaneous hepatic perfusion (PHP), in order to treat the entire liver as a standalone or as complementary therapy. This system isolates the liver circulation, delivers a high concentration of chemotherapy (melphalan), filters most chemotherapy out of the blood and is a repeatable procedure. Most CS-HDS benefits are demonstrated in liver-predominant diseases, like liver metastasis from uveal melanoma (UM), hepatocarcinoma (HCC) and CCA. More than 650 procedures have been performed in Europe to date, mostly to treat liver metastases from UM. In CCA, experience is still limited, but retrospective analyses have been reported, while phase II and III studies are closed, waiting for results or ongoing.
  • 511
  • 20 Jan 2021
Topic Review
Neuron–Glia Interaction in ENS
The enteric nervous system (ENS) constitutes the largest part of the peripheral nervous system.
  • 795
  • 19 Jan 2021
Topic Review
Selective Autophagy by Close Encounters
The aim of the review manuscript is to provide an over-view of the close relation between ubiquitin and the selective process of autophagy. We described how ubiquitin determine the selectivity towards different cellular component and how it may influence autophagy receptors activity. Precisely, we discussed the role of the ubiquitin signal in each type of selective autophagy.    
  • 476
  • 19 Jan 2021
Topic Review
GRKs
G protein-coupled receptor (GPCR) kinases (GRKs) play an important role in the regulation of signaling of GPCRs that bind neurotransmitters. The canonical model of GPCR desensitization posits that GRKs phosphorylate ligand-activated GPCRs, and this phosphorylation prepares receptors for the high-affinity binding of arrestin proteins. Arrestin binding prevents further G protein coupling, promotes receptor internalization, and initiates and/or facilitates specific branches of signaling. Existing data suggest that the role of GPCR phosphorylation by GRKs is distinct in different receptors. The relationship between G protein- and arrestin-mediated signaling on the one hand, and therapeutic and side effects of drugs on the other, is more complex than is widely believed. Also, the relationship between rapid (minutes to hours) GRK/arrestin-mediated regulation and long-term (days to weeks) neural plasticity remains to be elucidated. 
  • 1.2K
  • 19 Jan 2021
Topic Review
Limb Development
The function of retinoic acid (RA) during limb development is still debated, as loss and gain of function studies led to opposite conclusions. With regard to limb initiation, genetic studies demonstrated that activation of FGF10 signaling is required for the emergence of limb buds from the trunk, with Tbx5 and RA signaling acting upstream in the forelimb field, whereas Tbx4 and Pitx1 act upstream in the hindlimb field. Early studies in chick embryos suggested that RA as well as Meis1 and Meis2 (Meis1/2) are required for subsequent proximodistal patterning of both forelimbs and hindlimbs, with RA diffusing from the trunk, functioning to activate Meis1/2 specifically in the proximal limb bud mesoderm. However, genetic loss of RA signaling does not result in loss of limb Meis1/2 expression and limb patterning is normal, although Meis1/2 expression is reduced in trunk somitic mesoderm. More recent studies demonstrated that global genetic loss of Meis1/2 results in a somite defect and failure of limb bud initiation. Other new studies reported that conditional genetic loss of Meis1/2 in the limb results in proximodistal patterning defects, and distal FGF8 signaling represses Meis1/2 to constrain its expression to the proximal limb.
  • 1.1K
  • 19 Jan 2021
Topic Review
TKS4 and TKS5 Scaffold Proteins
Scaffold proteins are typically thought of as multi-domain “bridging molecules.” They serve as crucial regulators of key signaling events by simultaneously binding multiple participants involved in specific signaling pathways. In the case of epidermal growth factor (EGF)-epidermal growth factor receptor (EGFR) binding, the activated EGFR contacts cytosolic SRC tyrosine-kinase, which then becomes activated. This process leads to the phosphorylation of SRC-substrates, including the tyrosine kinase substrates (TKS) scaffold proteins. The TKS proteins serve as a platform for the recruitment of key players in EGFR signal transduction, promoting cell spreading and migration. The TKS4 and the TKS5 scaffold proteins are tyrosine kinase substrates with four or five SH3 domains, respectively. Their structural features allow them to recruit and bind a variety of signaling proteins and to anchor them to the cytoplasmic surface of the cell membrane. TKS4 and TKS5 had been recognized for their involvement in cellular motility, reactive oxygen species-dependent processes, and embryonic development. Furthermore, TKS4 has also been implicated in the regulation of homeostasis of mature adipose and bone tissue.
  • 712
  • 19 Jan 2021
Topic Review
MOB
The MOB family proteins are constituted by highly conserved eukaryote kinase signal adaptors involved in the regulation of cell cycle progression, cell proliferation versus proliferation, morphogenesis, and cell differentiation and are often essential both for cell and organism survival.
  • 786
  • 19 Jan 2021
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