Pancreatic ductal adenocarcinoma (PDA) is a highly aggressive tumor with limited treatment options. Zolbetuximab, a monoclonal antibody against the tight junction protein Claudin 18.2 has recently been developed.
View Article and Find Full Text PDFBackground/objectives: KRT23 was recently discovered as an epithelial-specific intermediate filament protein in the type I keratin family. Many studies have underlined keratin's involvement in several biological processes as well as in the pathogenesis of different diseases. Specifically, KRT23 was reported to affect the structural integrity of epithelial cells and to trigger cellular signaling leading to the onset of cancer.
View Article and Find Full Text PDFPinin (PNN) is a desmosome-associated protein that reinforces the organization of keratin intermediate filaments and stabilizes the anchoring of the cytoskeleton network to the lateral surface of the plasma membrane. The aberrant expression of PNN affects the strength of cell adhesion as well as modifies the intracellular signal transduction pathways leading to the onset of CRC. In our previous studies, we characterized the role of miR-195-5p in the regulation of desmosome junctions and in CRC progression.
View Article and Find Full Text PDFBackground: SMYD3 has been found implicated in cancer progression. Its overexpression correlates with cancer growth and invasion, especially in gastrointestinal tumors. SMYD3 transactivates multiple oncogenic mechanisms, favoring cancer development.
View Article and Find Full Text PDFDesmosomes are essential structures for ensuring tissue functions, and their deregulation is involved in the development of colorectal cancer (CRC). JUP (γ-catenin) is a desmosome adhesion component that also acts as a signaling hub, suggesting its potential involvement in CRC progression. In this context, we recently demonstrated that miR-195-5p regulated JUP and desmosome cadherins expression.
View Article and Find Full Text PDFIntroduction: Arterial wall viscosity is a source of energy dissipation that takes place during mechanical transduction. In our previous studies, a "global" damping effect in endurance training athletes was introduced, verifying that endurance-athletes dissipate greater pulsatile energy in the circulation compared with healthy untrained subjects.
Objective: To investigate the wall energy dissipation in the vascular bed for each beat and within the conceptual framework of ventricular-arterial coupling, in order to elucidate if different types of training could lead to differentiated levels of cardiovascular energy dissipation.
Desmosomes play a key role in the regulation of cell adhesion and signaling. Dysregulation of the desmosome complex is associated with the loss of epithelial cell polarity and disorganized tissue architecture typical of colorectal cancer (CRC). The aim of this study was to investigate and characterize the effect of miR-195-5p on desmosomal junction regulation in CRC.
View Article and Find Full Text PDFExtraintestinal manifestations occur rather frequently in ulcerative colitis (UC) and Crohn's disease patients and are usually related to an exacerbation of the underlying intestinal bowel disease but sometimes may run a course independent of the inflammatory bowel diseases (IBD). About one-third of patients with IBD develop extraintestinal manifestations, such as pyoderma gangrenosum (PG). PG is an uncommon inflammatory skin disorder of unknown pathogenesis.
View Article and Find Full Text PDFLynch syndrome (LS) is an inherited cancer susceptibility syndrome caused by germline mutations in a DNA mismatch repair (MMR) gene or in the gene. LS is associated with an increased lifetime risk of colorectal cancer (CRC) and other malignancies. The screening algorithm for LS patient selection is based on the identification of CRC specimens that have MMR loss/high microsatellite instability (MSI-H) and are wild-type for .
View Article and Find Full Text PDFMetastatic gastric cancer (mGC) often has a poor prognosis and may benefit from a few targeted therapies. Ramucirumab-based anti-angiogenic therapy targeting the VEGFR2 represents a milestone in the second-line treatment of mGC. Several studies on different cancers are focusing on the major VEGFR2 ligand status, meaning VEGFA gene copy number and protein overexpression, as a prognostic marker and predictor of response to anti-angiogenic therapy.
View Article and Find Full Text PDF[This corrects the article DOI: 10.1016/j.gendis.
View Article and Find Full Text PDFInflammasomes are multiprotein complexes expressed by immune cells in response to distinct stimuli that trigger inflammatory responses and the release of pro-inflammatory cytokines. Evidence suggests a different role of inflammasome NLRP3 in IBD. NLRP3 inflammasome activation can be controlled by post-translational modifications such as ubiquitination through BRCC3.
View Article and Find Full Text PDFInflammasome activation plays a crucial role in the progression to more severe stages of non-alcoholic fatty liver disease (NAFLD), representing a promising therapeutic target. MCC950 is a small molecule acting as a potent and specific inhibitor of the canonical and non-canonical activation of the NLRP3 inflammasome, but its short plasmatic half-life limits its use. Herein, we report, for the first time, the encapsulation of MCC950 in poly(ethylene glycol) (PEG) liposomes (LPs) that are specifically functionalized with an antibody against Frizzled 1 (FZD1), a g-coupled protein involved in the WNT pathway and overexpressed on inflammasome-activated macrophages.
View Article and Find Full Text PDFMany studies found that increased arterial stiffness is significantly associated with the presence and progression of Coronary Calcium Score (CCS). However, none so far have used machine learning algorithms to improve their value. Therefore, this study aims to evaluate the association between carotid-femoral Pulse Wave Velocity (cfPWV) and CCS score through computational clustering.
View Article and Find Full Text PDFAnaplastic classic Kaposi sarcoma (CKS) is an extremely rare pathologic variant of CKS characterized by high aggressiveness and poor prognosis. We report the clinical course of this malignant histologic form in an otherwise healthy 67-year-old male from Apulia in Southern Italy. The anaplastic progression arose during a long history of CKS and developed after multiple local and systemic treatments.
View Article and Find Full Text PDFArterial stiffness is a major condition related to many cardiovascular diseases. Traditional approaches in the assessment of arterial stiffness supported by machine learning techniques are limited to the pulse wave velocity (PWV) estimation based on pressure signals from the peripheral arteries. Nevertheless, arterial stiffness can be assessed based on the pressure-strain relationship by analyzing its hysteresis loop.
View Article and Find Full Text PDFThe aim of this study is to formulate a new methodology based upon informational tools to detect patients with cardiac arrhythmias. As it is known, sudden death is the consequence of a final arrhythmia, and here lies the relevance of the efforts aimed at the early detection of arrhythmias. The information content in the time series from an electrocardiogram (ECG) signal is conveyed in the form of a probability distribution function, to compute the permutation entropy proposed by Bandt and Pompe.
View Article and Find Full Text PDFColorectal cancer (CRC) is among the best examples for depicting the relationship between inflammation and cancer. The introduction of new therapeutics targeting inflammatory mediators showed a marked decrease in the overall risk of CRC, although their chemopreventive potential is still debated. Specifically, a monoclonal antibody that blocks tumor necrosis factor (TNF), infliximab, increases CRC risk in inflammatory bowel disease patients.
View Article and Find Full Text PDFBackground: Intrahepatic cholangiocarcinoma (iCCA) is a highly malignant tumor characterized by an intensive desmoplastic reaction due to the exaggerated presence of the extracellular (ECM) matrix components. Liver fibroblasts close to the tumor, activated by transforming growth factor (TGF)-β1 and expressing high levels of α-smooth muscle actin (α-SMA), become cancer-associated fibroblasts (CAFs). CAFs are deputed to produce and secrete ECM components and crosstalk with cancer cells favoring tumor progression and resistance to therapy.
View Article and Find Full Text PDFThe immunoproteasome is a multi-catalytic protein complex expressed in hematopoietic cells. Increased expression of immuno-subunits followed by increased proteasome activities is associated with the pathogenesis of IBD. Therefore, the identification of molecules that could inhibit the activities of this complex has been widely studied.
View Article and Find Full Text PDFSLC15A4/PHT1 is an endolysosome-resident carrier of oligopeptides and histidine recently come into view as a key path marker of immune/autoimmune/inflammatory pathways in immune cells. Yet, its emerging role in inflammatory processes directly targeting the gastrointestinal epithelial layer, as in the multifactorial pathophysiology of inflammatory bowel disease (IBD), is poorly investigated. Here, the first identification of gene products in human colonic epithelium of ulcerative colitis (UC) patients is reported, showing protein primarily localized in intracellular vesicle-like compartments.
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