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Topic Review
Cripto in scientific literature
Cripto is a small glycosylphosphatidylinisitol (GPI)-anchored and secreted oncofetal protein that plays important roles in regulating normal physiological processes, including stem cell differentiation, embryonal development, and tissue growth and remodeling, as well as pathological processes such as tumor initiation and progression. Cripto functions as a co-receptor for TGF-β ligands such as Nodal, GDF1, and GDF3. Soluble and secreted forms of Cripto also exhibit growth factor-like activity and activate SRC/MAPK/PI3K/AKT pathways. Glucose-Regulated Protein 78 kDa (GRP78) binds Cripto at the cell surface and has been shown to be required for Cripto signaling via both TGF-β and SRC/MAPK/PI3K/AKT pathways.
  • 525
  • 19 Oct 2020
Topic Review
Lipid Metabolism and Acylglycerolphosphate Acyltransferases (AGPATs) in Cancer
Alter lipid metabolism is an emerging hallmark of cancer. The conversion of fatty acids to neutral triacylglycerides (TAG), plays a central role in this adaptive process.  Acylglycerolphosphate acyltransferases (AGPATs)/lysophosphatidic acid acyltransferases (LPAATs) are a family of enzymes that catalyze the synthesis of phosphatidic acid (PA), an intermediate in TAG synthesis, a signaling molecule, and a precursor of phospholipids. Importantly, the expression of AGPATs has been linked to diverse physiological and pathological phenotypes, including cancer.
  • 525
  • 20 Jan 2022
Topic Review
Autophagy in Cell Survival and Cell Death
Autophagy is a process conserved from yeast to humans. Since the discovery of autophagy, its physiological role in cell survival and cell death has been intensively investigated. The inherent ability of the autophagy machinery to sequester, deliver, and degrade cytoplasmic components enables autophagy to participate in cell survival and cell death in multiple ways. The primary role of autophagy is to send cytoplasmic components to the vacuole or lysosomes for degradation. By fine-tuning autophagy, the cell regulates the removal and recycling of cytoplasmic components in response to various stress or signals. Autophagy also facilitates certain forms of regulated cell death. In addition, there is complex crosstalk between autophagy and regulated cell death pathways, with a number of genes shared between them, further suggesting a deeper connection between autophagy and cell death. Finally, the mitochondrion presents an example where the cell utilizes autophagy to strike a balance between cell survival and cell death.
  • 525
  • 22 Jul 2022
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.
  • 524
  • 20 Jan 2021
Topic Review
Metabolic Regulation of Mitochondrial Protein Biogenesis in neurons
Neurons critically depend on mitochondria for ATP production and Ca2+ buffering. They are highly compartmentalized cells and therefore a finely tuned mitochondrial network constantly adapting to the local requirements is necessary. For neuronal maintenance, old or damaged mitochondria need to be degraded, while the functional mitochondrial pool needs to be replenished with freshly synthesized components. Mitochondrial biogenesis is known to be primarily regulated via the PGC-1α-NRF1/2-TFAM pathway at the transcriptional level. However, while transcriptional regulation of mitochondrial genes can change the global mitochondrial content in neurons, it does not explain how a morphologically complex cell like a neuron adapts to local differences in mitochondrial demand. 
  • 524
  • 07 Nov 2022
Topic Review
Precision Medicine in Rare Diseases
The own patient-derived cells can be used to perform personalized pharmacological screening in genetic rare diseases. For precision medicine to be successful at the therapeutic level, in addition of the information provide from genomics, pharmacogenomics, metabolomics and proteomics, our proposal argues that it is also necessary to know the cellular response, and therefore the behavior of particular mutations in vitro, to various therapeutic options. Precision medicine relies on the assumption that different mutations and marked inter-individual genetic variation can contribute significantly to drug response. The goal of personalized medicine is to maximize the probability of therapeutic efficacy for an individual patient.
  • 524
  • 23 Nov 2020
Topic Review
Human Dental Pulp Stem Cells
Human dental pulp stem cells (hDPSCs) are adult mesenchymal stem cells (MSCs) obtained from dental pulp and derived from the neural crest. They can differentiate into odontoblasts, osteoblasts, chondrocytes, adipocytes and nerve cells, and they play a role in tissue repair and regeneration.
  • 523
  • 29 May 2023
Topic Review
STxB in Mucosal Vaccination
One mucosal vaccine candidate is the B-subunit of Shiga toxin, STxB. STxB is a non-toxic protein that binds to a glycosylated lipid, termed globotriaosylceramide (Gb3), which is preferentially expressed by dendritic cells. 
  • 522
  • 25 Mar 2022
Topic Review
Lactadherin in Cancer Development and Progression
Lactadherin is a secreted glycoprotein associated with the milk fat globule membrane, which is highly present in the blood and in the mammary tissue of lactating women. Several biological functions have been associated with this protein, mainly attributable to its immunomodulatory role promoting phagocyte-mediated clearance of apoptotic cells. It has been shown that lactadherin also plays important roles in cell adhesion, promotion of angiogenesis, and tissue regeneration. On the other hand, this protein has been used as a marker of breast cancer and tumor progression. Recently, high levels of lactadherin has been associated with poor prognosis and decreased survival, not only in breast cancer, but also in melanoma, ovarian, colorectal, and other types of cancer. Although the mechanisms responsible for the tumor-promoting effects attributed to lactadherin have not been fully elucidated, a growing body of literature indicates that lactadherin could be a promising therapeutic target and/or biomarker for breast and other tumors. Moreover, recent studies have shown its presence in extracellular vesicles derived from cancer cell lines and cancer patients, which was associated with cancer aggressiveness and worse prognosis. 
  • 522
  • 31 May 2022
Topic Review
Microglial Endocannabinoid Signalling in Alzheimer’s Disease
Chronic inflammation in Alzheimer’s disease (AD) has been recently identified as a major contributor to disease pathogenesis. Once activated, microglial cells, which are brain-resident immune cells, exert several key actions, including phagocytosis, chemotaxis, and the release of pro- or anti-inflammatory mediators, which could have opposite effects on brain homeostasis, depending on the stage of disease and the particular phenotype of microglial cells. The endocannabinoids (eCBs) are pleiotropic bioactive lipids increasingly recognized for their essential roles in regulating microglial activity both under normal and AD-driven pathological conditions. 
  • 522
  • 25 May 2022
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