Interleukin 3- receptor targeted exosomes inhibit in vitro and in vivo chronic myelogenous Leukemia cell growth
Despite Imatinib (IM), a selective inhibitor of Bcr-Abl, having led to improved prognosis in Chronic Myeloid Leukemia (CML) patients, acquired resistance and long-term adverse effects is still being encountered. There is, therefore, urgent need to develop alternative strategies to overcome drug resistance. According to the molecules expressed on their surface, exosomes can target specific cells. Exosomes can also be loaded with a variety of molecules, thereby acting as a vehicle for the delivery of therapeutic agents. In this study, we engineered HEK293T cells to express the exosomal protein Lamp2b, fused to a fragment of Interleukin 3 (IL3). The IL3 receptor (IL3-R) is overexpressed in CML…
Evaluation of a Cell-Free Collagen Type I-Based Scaffold for Articular Cartilage Regeneration in an Orthotopic Rat Model.
The management of chondral defects represents a big challenge because of the limited self-healing capacity of cartilage. Many approaches in this field obtained partial satisfactory results. Cartilage tissue engineering, combining innovative scaffolds and stem cells from different sources, emerges as a promising strategy for cartilage regeneration. The aim of this study was to evaluate the capability of a cell-free collagen I-based scaffold to promote cartilaginous repair after orthotopic implantation in vivo. Articular cartilage lesions (ACL) were created at the femoropatellar groove in rat knees and cell free collagen I-based scaffolds (S) were then implanted into right knee defect for the…
Multipotential Role of Growth Factor Mimetic Peptides for Osteochondral Tissue Engineering
Articular cartilage is characterized by a poor self-healing capacity due to its aneural and avascular nature. Once injured, it undergoes a series of catabolic processes which lead to its progressive degeneration and the onset of a severe chronic disease called osteoarthritis (OA). In OA, important alterations of the morpho-functional organization occur in the cartilage extracellular matrix, involving all the nearby tissues, including the subchondral bone. Osteochondral engineering, based on a perfect combination of cells, biomaterials and biomolecules, is becoming increasingly successful for the regeneration of injured cartilage and underlying subchondral bone tissue. To this end, recently,…
The phospholipase DDHD1 as a new target in colorectal cancer therapy
Background Our previous study demonstrates that Citrus-limon derived nanovesicles are able to decrease colon cancer cell viability, and that this effect is associated with the downregulation of the intracellular phospholipase DDHD domain-containing protein 1 (DDHD1). While few studies are currently available on the contribution of DDHD1 in neurological disorders, there is no information on its role in cancer. This study investigates the role of DDHD1 in colon cancer. Methods DDHD1 siRNAs and an overexpression vector were transfected into colorectal cancer and normal cells to downregulate or upregulate DDHD1 expression. In vitro and in vivo assays were performed to investigate the functional…
Galactosylated Polymer/Gold Nanorods Nanocomposites for Sustained and Pulsed Chemo-Photothermal Treatments of Hepatocarcinoma
In this paper, we propose a rational design of a hybrid nanosystem capable of locally delivering a high amount of hydrophobic anticancer drugs (sorafenib or lenvatinib) and heat (hyperthermia) in a remote-controlled manner. We combined in a unique nanosystem the excellent NIR photothermal conversion of gold nanorods (AuNRs) with the ability of a specially designed galactosylated amphiphilic graft copolymer (PHEA-g-BIB-pButMA-g-PEG-GAL) able to recognize hepatic cells overexpressing the asialoglycoprotein receptor (ASGPR) on their membranes, thus giving rise to a smart composite nanosystem for the NIR-triggered chemo-phototherapy of hepatocarcinoma. In order to allow the internalization of A…
PO-053 The phospholipase ddhd1 as a new target in colorectal cancer therapy
Introduction We have recently demonstrated that Citrus-limon derived nanovesicles are able to decrease colon cancer cell viability and that this effect is associated with the down-regulation of the intracellular phospholipase DDHD domain-containing protein 1 (DDHD1). While few studies are currently available on DDHD1 contribution in neurological disorders, information on its involvement in cancer is missing. Here we investigate the role of DDHD1 in colon cancer. Material and methods DDHD1 siRNAs and overexpression vector were transfected into colorectal cancer and normal cells to down-regulate or up-regulate DDHD1 expression. In vitro and in vivo assays were performed to investigate the fun…
A Curcumin-BODIPY Dyad and Its Silica Hybrid as NIR Bioimaging Probes
In this paper we describe the synthesis of a novel bichromophoric system in which an efficient photoinduced intercomponent energy transfer process is active. The dyad consists of one subunit of curcumin and one of BODIPY and is able to emit in the far-red region, offering a large Stokes shift, capable of limiting light scattering processes for applications in microscopy. The system has been encapsulated in MCM-41 nanoparticles with dimensions between 50 and 80 nm. Both the molecular dyad and individual subunits were tested with different cell lines to study their effective applicability in bioimaging. MCM-41 nanoparticles showed no reduction in cell viability, indicating their biocompatibil…
Retinoic Acid affects Lung Adenocarcinoma growth by inducing differentiation via GATA6 activation and EGFR and Wnt inhibition
AbstractA fundamental task in cancer research aims at the identification of new pharmacological therapies that can affect tumor growth. Differentiation therapy might exploit this function not only for hematological diseases, such as acute promyelocytic leukemia (APML) but also for epithelial tumors, including lung cancer. Here we show that Retinoic Acid (RA) arrests in vitro and in vivo the growth of Tyrosine Kinase Inhibitors (TKI) resistant Non Small Cell Lung Cancer (NSCLC). In particular, we found that RA induces G0/G1 cell cycle arrest in TKI resistant NSCLC cells and activates terminal differentiation programs by modulating the expression of GATA6, a key transcription factor involved …
Spectroscopic correlates of antidepressant response to sleep deprivation and light therapy: a 3.0 Tesla study of bipolar depression.
Glutamate is the primary excitatory neurotransmitter of the human brain, and recent findings suggest a role for the glutamatergic system in the pathophysiology and treatment of mood disorders. Single proton magnetic resonance spectroscopy (1H-MRS) was used to study the relative in vivo levels of brain neural metabolites. We evaluated the effect of antidepressant treatments on the relative concentration of unresolved glutamate and glutamine (Glx) with GABA contamination (2.35 ppm peak) using single voxel 1H-MRS at 3.0 Tesla. We studied 19 inpatients (7 males, 12 females) affected by bipolar disorder type 1, current depressive episode without psychotic features, before and after 1 week of tre…
Additional file 1: of The phospholipase DDHD1 as a new target in colorectal cancer therapy
Supplementary Material and Methods. (DOCX 24Â kb)
Cycloastragenol as an Exogenous Enhancer of Chondrogenic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells. A Morphological Study
Stem cell therapy and tissue engineering represent a promising approach for cartilage regeneration. However, they present limits in terms of mechanical properties and premature de-differentiation of engineered cartilage. Cycloastragenol (CAG), a triterpenoid saponin compound and a hydrolysis product of the main ingredient in Astragalus membranaceous, has been explored for cartilage regeneration. The aim of this study was to investigate CAG&rsquo
Additional file 3: of The phospholipase DDHD1 as a new target in colorectal cancer therapy
Table S1. Data from SWATH-MS Gene Ontology analysis. (XLSX 740Â kb)
Additional file 4: of The phospholipase DDHD1 as a new target in colorectal cancer therapy
Figure S2. Effects of DDHD1-expressing cells conditioned medium on DDHD1-silenced cell growth. Cell viability was measured by MTT assay on DDHD1-silenced SW480 cells in the presence of the conditioned medium (CM) of mock cells and DDHD1 overexpressing cells. (TIFF 3275Â kb)
Additional file 2: of The phospholipase DDHD1 as a new target in colorectal cancer therapy
Figure S1. DDHD1 silencing. To evaluate DDHD1 silencing a. Real-time PCR and b. Western blot analysis were performed on SW480, HCT116, HS5 and HUVEC transfected for 48 or 72Â h with scrambled siRNA or DDHD1 siRNA. (TIFF 6629Â kb)