Identification of CD24 as a potential diagnostic and therapeutic target for malignant pleural mesothelioma
CELL DEATH DISCOVERY
Authors: Karnan, Sivasundaram; Ota, Akinobu; Murakami, Hideki; Rahman, Lutfur; Hasan, Muhammad Nazmul; Wahiduzzaman; Hanamura, Ichiro; Lam Quang Vu; Inoko, Akihito; Hyodo, Toshinori; Konishi, Hiroyuki; Tsuzuki, Shinobu; Hosokawa, Yoshitaka
Abstract
Malignant pleural mesothelioma (MPM) is an aggressive malignancy of the pleura that is currently incurable due to the lack of an effective early diagnostic method and specific medication. The CDKN2A (p16) and NF2 genes are both frequently mutated in MPM. To understand how these mutations contribute to MPM tumor growth, we generated NF2/p16 double-knockout (DKO) cell clones using human MeT-5A and HOMC-B1 mesothelial cell lines. Cell growth and migration activities were significantly increased in DKO compared with parental cells. cDNA microarray analysis revealed differences in global gene expression profiles between DKO and parental cells. Quantitative PCR and western blot analyses showed upregulation of CD24 concomitant with increased phosphorylation of AKT, p70S6K, and c-Jun in DKO clones. This upregulation was abrogated by exogenous expression of NF2 and p16. CD24 knockdown in DKO cells significantly decreased TGF-beta 1 expression and increased expression of E-cadherin, an epithelial-mesenchymal transition marker. CD24 was highly expressed in human mesothelioma tissues (28/45 cases, 62%) and associated with the loss of NF2 and p16. Public data analysis revealed a significantly shorter survival time in MPM patients with high CD24 gene expression levels. These results strongly indicate the potential use of CD24 as a prognostic marker as well as a novel diagnostic and therapeutic target for MPM.
Water-in-Fluorocarbon Nanoemulsions Stabilized by Phospholipids and Characterized for Pharmaceutical Applications
ADVANCED MATERIALS INTERFACES
Authors: Ullmann, Kirsten; Meier, Manuel; Benner, Carolyn; Leneweit, Gero; Nirschl, Hermann
Abstract
Fluorocarbons are one of the most promising hydrophobic phases for future pharmaceutical production processes and various biomedical applications. Yet, because of their specific characteristics such as high density and refractive index similar to water, analysis of water-in-fluorocarbon (w/fc) nanoemulsions remains a challenge. The present work examines w/fc nanoemulsions stabilized with phospholipids as natural emulsifiers and tackles the measuring problems of photon correlation spectroscopy (PCS) when used for investigation of fluorocarbon nanoemulsions. These emulsions are suitable to form liposomes via centrifugation and thus, are required to meet certain criteria such as stability and size. The results imply a stability of up to 4 weeks with an average size of 180 nm. The intensity mean diameter gained from PCS measurements shows large scattering directly after sonication which is due to gas bubbles from sonication. The number mean is not influenced by gas bubbles and gives a more accurate depiction of the produced nanoemulsions. These findings are supported by small-angle X-ray scattering data, which are additionally applied for liposome analysis measuring a size of approximately 60 nm.