Concept of histone deacetylases in cancer: Reflections on esophageal carcinogenesis and treatment

Esophageal cancer (EC) presents a high mortality rate, mainly due to its aggressive nature. Squamous cell carcinoma is the most common histological type world-wide, though, a continuous increase in esophageal adenocarcinomas has been noted in the past decades. Common risk factors associated with EC include smoking, alcohol consumption, gastroesophageal reflux disease, Barrett's esophagus and obesity. In an effort to overcome chemotherapy resistance in oncology, it was discovered that histone acetylation/deacetylation equilibrium is altered in carcinogenesis, leading to changes in chromatin structure and altering expression of genes important in the cell cycle, differentiation and apoptosis. Based on this knowledge, histone acetylation was addressed as a potential novel chemotherapy drug target to repress cancer cell proliferation. There are four classes of histone deacetylases (HDACs) inhibitors with a variety of different mechanisms of actions that render them possible anticancer drugs. They arrest the cell cycle, inhibit differentiation and angiogenesis and induce apoptosis. They do not necessarily act on histone proteins, since they can also exert indirect anti-cancer effects, by modifying various cellular proteins.In addition,HDACs have also been associated with increased chemotherapy resistance.Based on the literature,HDACs have been associated with EC,with surveys revealing that increased expression of certain HDACs correlates with advanced TNM stages,tumor grade,metastatic potential and decreased 5-year overall and disease-free survival.The aim of this survey is to elucidate the molecular identity and mechanism of action of HDAC inhibitors as well as verify their potential utility as anti-cancer agents in esophageal cancer.     

Novel approaches for the treatment of ventricular tachycardia

Ventricular tachycardia(VT) is a crucial cause of sudden cardiac death(SCD) and a primary cause of mortality and morbidity in patients with structural cardiac disease. VT includes clinical disorders varying from benign to lifethreatening. Most life-threatening episodes are correlated with coronary artery disease, but the risk of SCD varies in certain populations, with various underlying heart conditions, specific family history, and genetic variants. The targets of VT management are symptom alleviation, improved quality of life, reduced implantable cardioverter defibrillator shocks, prevention of reduction of left ventricular function, reduced risk of SCD, and improved overall survival. Antiarrhythmic drug therapy and endocardial catheter ablation remains the cornerstone of guideline-endorsed VT treatment strategies in patients with structural cardiac abnormalities. Novel strategies such as epicardial ablation, surgical cryoablation, transcoronary alcohol ablation, pre-procedural imaging, and stereotactic ablative radiotherapy are an appealing area of res-earch. In this review, we gathered all recent advances in innovative therapies as well as experimental evidence focusing on different aspects of VT treatment that could be significant for future favorable clinical applications.     

Improving the practicality and safety of artificial corneas: Pre-assembly and gamma-rays sterilization of the Boston Keratoprosthesis

Purpose

To make the Boston keratoprosthesis (B-KPro), together with its carrier corneal graft, more easily procured, transported and stored, as well as less expensive, easier for the surgeon to implant and safer for the patient, it is proposed that the B-KPro-graft combination be pre-assembled by an expert technician, followed by sterilization with gamma ray irradiation (GI) allowing long-term storage at room temperature. For this to be possible, it must be shown that the B-KPro itself (not only the graft) remains unharmed by the irradiation.

Mitochondrial genome deletion aids in the identification of false- and true-negative prostate needle core biopsy specimens

We report the usefulness of a 3.4-kb mitochondrial genome deletion (3.4 mtdelta) for molecular definition of benign, malignant, and proximal to malignant (PTM) prostate needle biopsy specimens. The 3.4 mtdelta was identified through long-extension polymerase chain reaction (PCR) analysis of frozen prostate cancer samples. A quantitative PCR assay was developed to measure the levels of the 3.4 mtdelta in clinical samples. For normalization, amplifications of a nuclear target and total mitochondrial DNA were included. Cycle threshold data from these targets were used to calculate a score for each biopsy sample. In a pilot study of 38 benign, 29 malignant, and 41 PTM biopsy specimens, the difference between benign and malignant core biopsy specimens was well differentiated (P & .0001), with PTM indistinguishable from malignant samples (P = .833). Results of a larger study were identical. In comparison with histopathologic examination for benign and malignant samples, the sensitivity and specificity were 80% and 71%, respectively, and the area under a receiver operating characteristic (ROC) curve was 0.83 for the deletion. In a blinded external validation study, the sensitivity and specificity were 83% and 79%, and the area under the ROC curve was 0.87. The 3.4 mtdelta may be useful in defining malignant, benign, and PTM prostate tissues.     

Apolipoprotein E gene polymorphism in psoriasis

Polymorphism in the apolipoprotein E gene has been associated with several neurological, cardiological and ophthalmological diseases. Apolipoprotein E is involved in psoriasis by modifying mitogen-activated T lymphocyte proliferation and by assuring protection against some infections. We evaluated the apolipoprotein E gene polymorphism in patients suffering from psoriasis (compared to matched controls) in Thrace, Northern Greece. One hundred and forty patients suffering from psoriasis vulgaris and 155 matched controls were included in this study and genotyped by semi-nested polymerase chain reaction RFLPs; the results were evaluated by conditional logistic regression. In psoriasis vulgaris patients, the e2 allele showed higher frequency (6.1%, P = 0.021) versus matched controls (2.3%). The above data were ascertained particularly enforced in psoriasis vulgaris male patients (P = 0.031) as well as in late onset psoriasis vulgaris (P = 0.029). Implication of apolipoprotein E in the pathogenesis of psoriasis has been indicated. Allele e2 is more frequent in psoriatic patients and its presence is more evident in late onset psoriasis vulgaris.