Nucleosome reorganisation in breast cancer tissues.

BACKGROUND: Nucleosome repositioning in cancer is believed to cause many changes in genome organisation and gene expression. Understanding these changes is important to elucidate fundamental aspects of cancer. It is also important for medical diagnostics based on cell-free DNA (cfDNA), which originates from genomic DNA regions protected from digestion by nucleosomes. RESULTS: We have generated high-resolution nucleosome maps in paired tumour and normal tissues from the same breast cancer patients using MNase-assisted histone H3 ChIP-seq and compared them with the corresponding cfDNA from blood plasma. This analysis has detected single-nucleosome repositioning at key regulatory regions in a patient-specific manner and common cancer-specific patterns across patients. The nucleosomes gained in tumour versus normal tissue were particularly informative of cancer pathways, with ~ 20-fold enrichment at CpG islands, a large fraction of which marked promoters of genes encoding DNA-binding proteins. The tumour tissues were characterised by a 5-10 bp decrease in the average distance between nucleosomes (nucleosome repeat length, NRL), which is qualitatively similar to the differences between pluripotent and differentiated cells. This effect was correlated with gene activity, differential DNA methylation and changes in local occupancy of linker histone variants H1.4 and H1X. CONCLUSIONS: Our study offers a novel resource of high-resolution nucleosome maps in breast cancer patients and reports for the first time the effect of systematic decrease of NRL in paired tumour versus normal breast tissues from the same patient. Our findings provide a new mechanistic understanding of nucleosome repositioning in tumour tissues that can be valuable for patient diagnostics, stratification and monitoring.

The Effect of Poly (Ethylene glycol) Emulation on the Degradation of PLA/Starch Composites.

As a hydrophilic renewable polymer, starch has been widely used in biocompatible plastics as a filler for more than two decades. The present study aimed at investigating the effects of polyethylene glycol (PEG), as a plasticizer, on the physicochemical properties of a hybrid composite-polylactic acid (PLA) and thermoplastic starch (TPS). A solvent evaporation process was adopted to gelatinize the starch and disparate PEG contents ranging from 3 to 15 wt.% (with respect to the sample weight) were examined. It was revealed that the increase in the PEG content was accompanied by an increment in the starch gelatinization degree. Referring to the microstructural analyses, the TPS/PLA mixture yielded a ductile hybrid composite with a fine morphology and a uniform phase. Nevertheless, two different solvents, including acetone and ethanol, were used to assess if they had any effect on the hybrid's morphology, tensile strength and thermal properties. It was found that ethanol culminated in a porous hybrid composite with a finer morphology and better starch distribution in the PLA structure than acetone. As the result of PEG addition to the composite, the crystallinity and tensile strength were decreased, whereas the elongation increased. The hydrolytic degradation of samples was assessed under different pH and thermal conditions. Moreover, the microbial degradation of the PLA/TPS hybrid composite containing different PEG molar fractions was investigated in the soil for 45 days. The rate of degradation in both hydrolytic and biodegradation increased in the samples with a higher amount of PEG with ethanol solvent.

MGMT activity in mucosal epithelium and squamous cell carcinoma of the head and neck.

UNLABELLED: Smoking and alcohol abuse cause squamous cell carcinoma of the head and neck (SCCHN) through smoke-induced mutations, which are counteracted by O(6)-methylguanine-DNA methyltransferase (MGMT). This study aimed at elucidating the role of MGMT in SCCHN and its precursor lesions (SIN). MGMT was also determined in the normal mucosa (NM) and blood lymphocytes (PBLCs). RESULTS: a) MGMT was lower in NM than in PBLCs. b) Smoking reduced MGMT in NM but had no effect in PBLCs. c) MGMT activity increased in the sequence NM