Metabolic dependence of cyclosporine  A on cell proliferation of human non‑small cell lung cancer A549 cells and its implication in post‑transplant malignancy.

Metabolic dependence of cyclosporine A on cell proliferation of human non‑small cell lung cancer A549 cells and its implication in post‑transplant malignancy. Oncol Rep. 2019 Mar 18;: Authors: Qin X, Chen Z Abstract Cyclosporine A (CsA), a widely used immunosuppressant to prevent organ transplant rejection, is associated with an increased cancer risk following transplantation, particularly in the lung. However, the underlying mechanisms remain unclear. In the present study, using human non‑small cell lung cancer A549 cells, it was determined that CsA (0.1 or 1 µM) promoted cell proliferation with glucose alone as the energy source. CsA treatment increased the phosphorylation of protein kinase B (Akt) and consequently the expression of Cyclin D1. Inhibiting Akt signaling with the phosphatidylinositol 3‑kinase inhibitor wortmannin prevented this effect. Mechanistically, CsA treatment increased reactive oxygen species (ROS) generation, and the intracellular ROS scavenger N‑acetyl‑cysteine (NAC) attenuated CsA‑induced cell proliferation as well as the activation of Akt/Cyclin D1 signaling. However, notably, it was demonstrated that CsA treatment decreased cell proliferation and Akt phosphorylation under normal lipid loading. Further investigation indicated that palmitic acid induced excessive generation of ROS, while CsA treatment further stimulated this ROS production. Scavenging intracellular ROS with NAC at...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research

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Conclusion: This study suggests that a clinically efficacious cardiovascular Chinese herbal medicine (DLP) can be successfully repurposed to treat a lung disease in pulmonary fibrosis guided by TCM theory. Our comparative study between DLP and DHP demonstrated a critical requirement of suppressing both pro-inflammatory and pro-fibrotic pathways for the treatment of pulmonary fibrosis, supporting that a multi-component prescription capable of “removing both phlegm and blood stasis” will better achieve co-protection of heart and lung in PHD. Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic an...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 18 April 2019Source: Journal of Sport and Health ScienceAuthor(s): Xin Luan, Xiangyang Tian, Haixin Zhang, Rui Huang, Na Li, Peijie Chen, Ru WangAbstractA growing understanding of the benefits of exercise over the past few decades has prompted researchers to take an interest in the possibilities of exercise therapy. Because each sport has its own set of characteristics and physiological complications that tend to appear during exercise training, the effects and underlying mechanisms of exercise remain unclear. Thus, the first step in probing exercise effects on different diseases is the s...
Source: Journal of Sport and Health Science - Category: Sports Medicine Source Type: research
Conclusions MDSC are major players in the immunosuppressive scenario in cancer, thanks to their phenotype heterogeneity and critical interaction with several innate immune cells, thus representing a crucial target in oncology. Here we reviewed the interactions of MDSCs with NK cells. The contribution of key cytokines, chemokines and mediators active in this process have been discussed. We also described the contribution of MDSC on angiogenesis directly or indirectly through interactions with NK and immunosuppressive activities. A parallel of the cancer associated to the decidual counterpart of these cells is discussed, a...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions and Perspectives In this review, we have discussed important milestones from the early description of “Serum-sickness” as being due to antibodies directed against Neu5Gc epitopes all the way to the present-day therapeutic implications of these antibodies in cancer therapy. Some of these milestones have been represented in a concise timeline (Figure 6). While the “Xenosialitis” hypothesis is well-supported in the human-like mouse models, it has yet to be conclusively proven in humans. It remains to be seen if “Xenosialitis” plays a role in other uniquely-human diseases. FI...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In this study, we aimed to investigate the potential anti-proliferative and pro-apoptotic activities of SNG in a panel of MM cell lines (U266, IM9, MM1S, and RPMI-8226). SNG treatment of MM cells resulted in a dose-dependent decrease in cell viability through mitochondrial membrane potential loss and activation of caspase 3, 9, and cleavage of PARP. Pre-treatment of MM cells with a universal caspase inhibitor, Z-VAD-FMK, prevented SNG mediated loss of cell viability, apoptosis, and caspase activation, confirming that SNG-mediated apoptosis is caspase-dependent. The SNG-mediated apoptosis appears to be resulted from suppres...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In this study, several biopsies from a patient-derived primary renal-cell carcinoma were analyzed by whole-exome sequencing and aligned to healthy tissue. Next to several shared mutations between different subclones, ca. 23% of the mutations were only found in specific regions of the tumor. Strikingly, a single biopsy of that same tumor only covered around 55% of the total mutational diversity, underlining the need for multi-region sampling. Tracing the order of mutations in different subclones revealed that they develop in a branching fashion from the primary tumor clone, harboring the driver mutation, rather than in a li...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In this study they also showed PTX3 localized in NETs formed after neutrophil activation (5). Proteomics analysis revealed that PTX3 forms complexes with two anti-microbial proteins [azurocidin (AZU1) and myeloperoxidase (MPO)] associated to NETs (30). More recently, PTX3 localization in NETs has been confirmed, and the colocalization with AZU1 and MPO has been defined more accurately (31). Further investigation will be needed to understand the involvement of PTX3 interaction with AZU1 and MPO in their antibacterial role during NET formation. Regulation of Complement Activation PTX3 interaction with microorganisms is not...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Discussion Suppressor of cytokine signaling 1 is an essential molecule for maintaining immune homeostasis and subverting inflammation. Disorders arising from excess inflammation or SOCS1 deficiency can be potentially treated with SOCS1 mimetics (Ahmed et al., 2015). While SOCS1 has promising potential in many disorders, it should be noted that new targets and actions of SOCS1 are still being discovered and not all the effects of this protein are beneficial in autoimmune diseases and cancer. For instance, SOCS1 degrades IRS1 and IRS2, required for insulin signaling, via the SOCS Box domain, thus, limiting its potential in ...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusions: CAR T cell therapies have demonstrated the clinical benefits of harnessing our body's own defenses to combat tumor cells. Similar research is being conducted on lesser known modifications and gene-modified immune cells, which we highlight in this review. Introduction Chimeric antigen receptors and engineered T cell receptors (based on previously identified high affinity T cell receptors) function by redirecting T cells to a predefined tumor-specific (or tumor-associated) target. Most of these modifications use retroviral or lentiviral vectors to integrate the construct, and most of the receptors ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Monica Parodi1, Herman Favoreel2, Giovanni Candiano3, Silvia Gaggero4, Simona Sivori4,5, Maria Cristina Mingari1,4,5, Lorenzo Moretta6, Massimo Vitale1 and Claudia Cantoni4,5,7* 1Immunology Operative Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy 2Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium 3Laboratory of Molecular Nephrology, IRCCS Istituto Giannina Gaslini, Genoa, Italy 4Department of Experimental Medicine, University of Genoa, Genoa, Italy 5Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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