Current Molecular Medicine - Volume 17, Issue 10, 2017

Several studies have investigated the risk factors associated with asthma. Both genetic and environmental factors are considered to contribute to asthma susceptibility. Individual genetic association studies usually suffer from small sample size leading to biased results. Meta-analysis is a powerful tool that has the potential to resolve this limitation by increasing the statistical power of analyses. The current review summarizes the recent knowledge concerning genetic factors involved in asthma predisposition based on meta-analyses. Using the keywords: asthma, meta-analysis, polymorphism, we searched Pubmed, Medline, Embase and Google Scholar databases for the associated articles. Genetic polymorphisms in twenty-three genes are associated with asthma risk in meta-analyses. However, polymorphisms in nine genes showed none significant association. These findings are used to assess the genetic risk factors and to understand the molecular pathways related to asthma.

The initial uses of ultrasound waves in the medical field were limited to the thermal ablation of solid tumors and as a diagnostic tool. Recent advances at the preclinical stage have allowed the use of ultrasound as a powerful tool to improve drug delivery when the agent is administered encapsulated inside a nanoparticle. This spatial and temporal control of drug release, using a non-invasive modality, is a promising approach to decrease the side effects of conventional chemotherapy in cancer treatments, as it reduces the interaction of the anti-neoplastic agent with healthy tissues. In this review, we explain the physics of ultrasound, introduce and discuss several examples on the use of nanoparticles as drug carriers, with a focus on liposomes. Examples of in vitro and in vivo studies are presented and discussed.

Background: Tumor-infiltrating lymphocytes (TILs) are one of the major participants in the tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC). However, the mechanism of interaction between TILs and tumors is complex and remains unclear. Objective: To evaluate the state of immunoreactions in PDAC tissues, and explore the prognostic value of these markers in a large sample, to provide a new theoretical basis for PDAC immunotherapy. Method: Immunohistochemical staining of CD4+ and CD8+T cells was performed in a tissue microarray (TMA) of 143 cases of PDAC. Two major variables for the spatial distributions of CD4+T and CD8+T cells in PDAC tissues, intraepithelial attack and intratumoral infiltration, were used to evaluate the state of immunoreactions, and the interrelationships with the clinicopathological variables were analyzed. Results: Our data showed that both the intraepithelial CD4+T and CD8+T attack were less frequent than the intratumoral infiltration. CD8+T intraepithelial attack and intratumoral infiltration were more intense than CD4+T. CD8+T intraepithelial attack was an independent favorable prognostic factor for overall survival, correlating negatively with vascular invasion and positively with CD4+T and CD8+T high intratumoral infiltration. CD8+T high intratumoral infiltration without CD8+T intraepithelial attack was a poor prognostic factor. CD8+T high intratumoral infiltration was accompanied by T stage progression. Conclusively, in PDAC progression, imbalances of T cells occurred in CD4+ and CD8+ immunoreactions. The CD8+T intraepithelial attack was an independent favorable prognostic indicator, however the intraepithelial attack of CD4+T and the both intratumoral infiltration of CD8+T and CD4+T played an ambiguous role. Conclusion: Our data suggested that it is a potential approach to increasing the number of intraepithelial attacking CD8+T cells for tumor immunotherapy, and exploring a new mechanism for immunosuppression in a tumor microenvironment with high T cell infiltration without attack.

Background: Ceramide plays critical roles in cell proliferation, senescence and apoptosis, and is implicated in neurodegenerative diseases, etc. To clarify if ceramide plays some roles in retinal diseases, we established in vivo and in vitro retinal injury models with ceramide 2 (C2) treatment. In addition, Erythropoietin (EPO), which showed protective effects on retinal cells and blood-retinal barrier (BRB), was also tested for its protection and possible mechanism(s) in these models. Methods: Male Sprague-Dawley rats were divided into four groups, i.e., normal control, vehicle control, C2 treatment, and C2+EPO treatment. After intravitreal injection, the rats were examined for eye fundus, electroretinogram, histological study, and immunostaining, etc. In vitro, retinal neuronal cell line (R28) and the primary human retinal microvascular endothelial cells (HRMECs) were treated with C2, cell viability assay, transendothelial electrical resistance (TEER) and BRB-related molecules were studied to test the protective effect of EPO. Results: Intravitreal C2-treatment caused significant vision loss in rats, as reflected by reduced b-wave amplitude, increased TUNEL positive cells and GFAP immunostaining in retina. Another major retinal injury observed was BRB breakdown following C2- treatment. Such C2-induced injuries were further confirmed by in vitro study. When HRMECs were treated with C2, the TEER was significantly reduced. The mechanisms for C2 to induce such injuries might be through evidently increased expressions of the related molecules like plasmalemma vesicle-associated protein (PLVAP or PV-1), ecto- 5'-nucleotidase (CD73) and intercellular adhesion molecule-1 (ICAM-1), as observed in C2-treated R28 cells. All these injuries induced by C2 were significantly prevented by EPO both in vivo and in vitro, and its protective mechanisms here might be, in addition to neuroprotective, closely related to its maintenance of BRB integrity, through reducing the expressions of PV-1, CD73 and ICAM-1. Conclusion: C2 could induce severe retinal injury, and such injuries could be effectively prevented by EPO treatment.

Background: In the last decades, survival rates in head and neck squamous cell carcinoma (HNSCC) have not changed, with a five-year survival of only 50%. Thus, there is a great need for the identification of new molecular targets and development of novel therapeutic strategies. Cancer-testis antigens (CTAs) are expressed in various types of tumor but rarely in healthy normal tissues. Therefore, they appear as ideal targets for immunotherapy approaches, as well as, unique markers for cancer diagnosis/prognosis. Objective: This study evaluated the expression pattern of cancer/testis antigens (CTA) in HNSCC samples and correlated the expression data with the clinicopathological prognostic variables. Methods: An in silico screening was performed using all CTA genes cataloged on the CTDatabase and the expression of the eight CTA genes (ARMC3, DDX53, FTHL17, GAGE1, MAGEA11, SYCE1, TCP11, and XAGE1) was examined in 89 HNSCC and 20 normal mucosa samples using RT-PCR analysis. Results: GAGE1 (48.3%), XAGE1 (40.4%) and MAGEA11 (19.1%) were frequently and specifically expressed in HNSCC samples and 68.5% of the cases expressed at least one of these antigens. Moreover, GAGE1 and XAGE1 mRNA positivity was significantly associated with the presence of metastasis in the lymph nodes (p=0.038 and p=0.023, respectively) and, by multivariate analysis, male gender (p=0.032), advanced clinical stage (p=0.018) and mRNA positivity for GAGE1 (p=0.010) were independent prognostic factors for overall survival. Conclusion: These findings suggest GAGE1 and XAGE1 expressions to be useful as prognostic markers for HNSCC.