Stressors alter intercellular communication and exosome profile of nasopharyngeal carcinoma cells.

BACKGROUND: Head and neck cancers comprise the sixth most common cancer type worldwide. One of the most remarkable malignancies of the head and neck is the cancer of the nasopharynx, with a strong metastatic tendency already in the early stage. Besides the conventional pathways of metastasis formation, the information content of exosomes produced by the cancer cells may play a key role in metastatic transformation. The aim of this study was to investigate how stressors alter the characteristic of tumor derived exosomes. METHODS: In our experimental model, we compared the quantity and content of exosomes produced by a nasopharyngeal carcinoma cell line (5-8F) under conventional (chemotherapy) and alternative (Ag-TiO2 -catalyzed reactive oxygen species generation) cytostatic treatment. After isolation, exosomes were identified by atomic force microscopy and quantified with Nanosight NS500 device. MicroRNA content of them was analyzed using SOLiD 5500xl technology. The sequences were annotated in CLC Genomics Workbench version 5.5.1. RESULTS: Beyond the classic chemotherapeutic agent (doxorubicin), Ag-TiO2 in a photo-catalytic process also showed cytostatic activity. Tumor cell damage induced by the cytostatic treatments significantly altered the number of released exosomes and led to the predominance of tumor suppressors in the exosomal miRNA profile. CONCLUSIONS: Our results suggest that the intercellular communication between tumor cells and surrounding stroma cells can be altered by microenvironment which increased quantity of exosomes and diversity of miRNAs in this study. Imbalance of oncogenic and tumor suppressor miRNAs caused by cytostatic treatments may influence the antiproliferative and metastasis inhibitory effect of cytostatic agents.

Volatile sulphur compound measurement with OralChroma(TM): a methodological improvement.

The instrumental measurement of volatile sulphur compounds is a common practice to assess halitosis. One of the most widespread devices for that purpose is OralChroma(TM), a combination of a semiconductor gas sensor and a compact gas chromatograph (GC) system. Several lines of evidence indicate that although the hardware of OralChroma(TM) is fit for the precise measurement of volatile sulphur compounds (VSCs), its software needs revision to allow that precision. In this study we sought to develop software to solve this problem, and to test the utility of the new software in a population of patients and controls. The results were also compared with VSC measurements performed with Halimeter(®), another widespread device, so as to assess the correlation. A set of measurements involving volunteers (21 controls and 14 oral cancer patients) were conducted. The analysis of the chromatograms recorded by OralChroma(TM) indicated that the majority of the studied breath samples contained significant amounts of isoprene (the peak was around 100 s) and acetaldehyde (the peak was around 350 s), therefore OralChroma(TM) was also calibrated for both isoprene and acetaldehyde. A linear relationship was found between the concentration (in the range of 80-1400 ppbv for acetaldehyde and 40-560 ppbv for isoprene) and the area under the corresponding peak. In numerous cases the concentrations of VSCs calculated by the software of OralChroma(TM) required revision. In the new software, the concentrations of the VSCs, isoprene and acetaldehyde were determined by fitting the chromatograms with the sum of six Gaussian functions. Based on the findings of the present study we conclude that our new software allows an improved and instantaneous evaluation of OralChroma(TM) chromatograms with the additional possibility of determining the isoprene and acetaldehyde concentrations from breath samples.

Role of epigenetics in EBV regulation and pathogenesis.

Epigenetic modifications of the viral and host cell genomes regularly occur in EBV-associated lymphomas and carcinomas. The cell type-dependent usage of latent EBV promoters is determined by the cellular epigenetic machinery. Viral oncoproteins interact with the very same epigenetic regulators and alter the cellular epigenotype and gene-expression pattern: there are common gene sets hypermethylated in both EBV-positive and EBV-negative neoplasms of different histological types. A group of hypermethylated promoters may represent, however, a unique EBV-associated epigenetic signature in EBV-positive gastric carcinomas. By contrast, EBV-immortalized B-lymphoblastoid cell lines are characterized by genome-wide demethylation and loss and rearrangement of heterochromatic histone marks. Early steps of EBV infection may also contribute to reprogramming of the cellular epigenome.