microRNA profiling for early detection of nonmelanoma skin cancer.

BACKGROUND: microRNAs (miRNAs) are single-stranded, noncoding RNA molecules. Given the vast regulatory potential of miRNAs and their often tissue-specific and disease-specific expression patterns, miRNAs are being assessed as possible biomarkers to aid diagnosis and prediction of different types and stages of cancers, including skin cancer. Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common forms of nonmelanoma skin cancer (NMSC). BCC originates from the basal layer of the epidermis, while SCC arises from epidermal keratinocytes or from the dermal appendages. Although NMSCs are currently the most common types of malignancies, both BCC and SCC have a better than 95% cure rate if detected early. AIM: To identify plasma miRNAs suitable for early detection of NMSC. METHODS: Expression profiles of 741 miRNAs were evaluated using high-throughput real-time quantitative PCR from plasma samples in 42 patients with NMSC and 282 healthy controls (HCs). RESULTS: Our results demonstrated that in patients with NMSC, compared with HCs, expression levels of miR-30e-3p, miR-145-5p, miR-186-5p and miR-875-5p were significantly (P < 0.05) upregulated, while those of miR-19a-3p, miR-25-3p, miR-30a-5p, miR-451 and miR-576-3p were significantly downregulated. CONCLUSION: Our study suggests that the miRNAs with significant changes in expression (miR-19a-3p, miR-25-3p, miR-30a-5p, miR-145-5p and miR-186-5p) could serve as novel noninvasive biomarkers for detection of NMSC.

Effects of intravitreal injection of bevacizumab on nitric oxide levels.

PURPOSE: This study aimed to determine the possible effects of single-dose intravitreal bevacizumab on nitric oxide (NO) levels in serum and remote organs and to reveal one of the possible mechanisms in the pathophysiology of hypertension. METHODS: Thirty-eight adult New Zealand albino rabbits were divided into a control group (no injection was performed, killed on day 28 of the study), group 1 (killed on day 1 of the study), group 2 (killed on day 7 of the study), group 3 (killed on day 14 of the study), and group 4 (killed on day 28 of the study). The right eyes of the animals in groups 1-4 received an intravitreal single injection of 1.25 mg (0.05 ml) bevacizumab (Avastin), and their brain, heart, liver, kidney, and blood samples were collected. NO levels were evaluated in the serum and organ homogenates. Kidney tissues were assessed by electron microscopy. RESULTS: Serum, brain, kidney, and liver NO levels significantly decreased in groups 2, 3, and 4 as compared with the control group (P<0.05). In addition, heart NO levels significantly decreased in groups 3 and 4 compared with the control group (P<0.05). There were no electron microscopic changes in the kidneys of either group. CONCLUSIONS: This study demonstrated that single intravitreal injection of bevacizumab decreased NO levels in serum, brain, heart, liver, and kidneys. In addition, there were no electron microscopic changes in the kidneys.

Circulating microRNA expression profiles in ovarian cancer.

MicroRNA (miRNA) is an abundant class of small non-coding RNAs that act as gene regulators. Recent studies have suggested that miRNA deregulation is associated with the initiation and progression of human cancer. However, information about ovarian cancer-related miRNA is mostly limited to tissue miRNA. The aim of this study was to find specific profiles of plasma-derived miRNAs of ovarian cancer. In this present study, the expression profiles of 740 miRNAs in plasma from 18 patients and 24 healthy women subjects were evaluated using microfluidic based multiplex qRT-PCR. Our results demonstrated that expression levels of eight miRNAs were significantly upregulated in patients with ovarian cancer when compared with a control group (p < 0.05). Expression levels of four miRNAs were found significantly downregulated in patients with ovarian cancer (p < 0.05). In addition, 10 miRNAs were expressed only in the ovarian cancer group and miR-138-5p of these miRNAs is ovarian specific. In conclusion, our study suggests that detecting these ovarian cancer specific miRNAs in plasma might serve as novel non-invasive biomarkers for ovarian cancer.

N-acetylcysteine ameliorates nitrosative stress on radiation-inducible damage in rat liver.

PURPOSE: The present study was designed to investigate the potential radioprotective effects of N-acetylcysteine (NAC) on radiation-induced nitrosative stress caused by gamma irradiation (single dose, 6 Gy) in rat liver. METHODS: The rats (n=40) were divided randomly and equally into 4 groups: Control (C), Radiation (R), R+NAC (received irradiation and 1,000 mg/kg of NAC) and R+WR-2721 (received irradiation and 200 mg/kg of WR-2721). Liver tissue of each animal was harvested and utilized for 3-nitrotyrosine (3-NT) detection using high-performance liquid chromatography- ultraviolet (HPLC-UV) system. RESULTS: In the R rats, 3-NT levels significantly increased when compared to those of the C rats (p<0.05). There were no significant differences in the 3-NT levels among R+NAC and R+WR-2721 rats. Histologically examined liver tissue samples showed no obvious differences. CONCLUSION: The present study suggests that irradiation has a negative effect on the cellular proteins by enhancing 3-NT formation. The prophylactic use of NAC seems to reduce the nitrosative damage during radiotherapy.

Role of CYP2C9 and CYP2C19 polymorphisms in patients with atherosclerosis.

The arachidonic acid metabolizing CYP enzymes with prominent roles in vascular regulation are epoxygenases of the two gene family which generate epoxyeicosatrienoic acids. Carriers of CYP2C9 mutant alleles exhibit a diminished CYP2C9 metabolic capacity leading to decreased endothelium-derived hyperpolarizing factors (EDHF) synthesis and an increased risk for atherosclerosis. We investigated whether the polymorphisms of CYP2C9/19 are related with atherosclerosis. We examined 108 patients having angioraphically > or =70 coronary artery narrowing and 90 healthy controls. CYPC2C9/19*2 and CYP2C9/19*3 alleles were investigated in both patients and controls by a real time PCR instrument. There was no significant difference in the distribution of the CYP2C9*2/*3 alleles between cases and the controls. We found that smoker patients having CYP2C9*2 heterozygote genotype have 3.7-fold risk of developing atherosclerosis. CYP2C19*3 heterozygote alleles are more frequent in patients than in controls (10.2%, 5.6% respectively) and it is related with a three-fold risk of atherosclerosis (odds ratio (OR) = 3.75, confidence interval (CI) = 0.75-18.65). It becomes clear that cigarette smoking can cause almost all major diseases prevalent today, such as cancer or heart disease. This inter-subject variability in cigarette-induced pathologies is partly mediated by genetic variants of genes that may participate in detoxification processes, e.g., cytochrome P450 (CYP), cellular susceptibility to toxins, such as p53, or disease development such as atherosclerosis.