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Unresectable neuroendocrine neoplasms (NENs) often poorly respond to standard therapeutic approaches. Alkylating agents, in particular temozolomide, commonly used to treat high-grade brain tumors including glioblastomas, have recently been tested in advanced or metastatic NENs, where they showed promising response rates. In glioblastomas, prediction of response to temozolomide is based on the assessment of the methylation status of the MGMT gene, as its product, O6 -methylguanine-DNA methyltransferase, may counteract the damaging effects of the alkylating agent. However, in NENs, such a biomarker has not been validated yet. Thus, we have investigated MGMT methylation in 42 NENs of different grades and from various sites of origin by two different approaches: in contrast to methylation-specific PCR (MSP), which is commonly used in glioblastoma management, amplicon bisulfite sequencing (ABS) is based on high-resolution, next-generation sequencing and interrogates several additional CpG sites compared to those covered by MSP. Overall, we found MGMT methylation in 74% (31/42) of the NENs investigated. A higher methylation degree was observed in welldifferentiated tumors and in tumors originating in the gastrointestinal tract. Comparing MSP and ABS results, we demonstrate that the region analyzed by the MSP test is sufficiently informative of the MGMT methylation status in NENs, suggesting that this predictive parameter could routinely be interrogated also in NENs.  相似文献   
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It is well recognized that the world population is ageing rapidly. Therefore, it is important to understand ageing processes at the cellular and molecular levels to predict the onset of age‐related diseases and prevent them. Recent research has focused on the identification of ageing biomarkers, including those associated with the properties of the Golgi apparatus. In this context, Golgi‐mediated glycosylation of proteins has been well characterized. Additionally, other studies show that the secretion of many compounds, including pro‐inflammatory cytokines and extracellular matrix–degrading enzymes, is modified during ageing, resulting in physical and functional skin degradation. Since the Golgi apparatus is a central organelle of the secretory pathway, we investigated its structural organization in senescent primary human dermal fibroblasts using confocal and electron microscopy. In addition, we monitored the expression of Golgi‐related genes in the same cells. Our data showed a marked alteration in the Golgi morphology during replicative senescence. In contrast to its small and compact structure in non‐senescent cells, the Golgi apparatus exhibited a large and expanded morphology in senescent fibroblasts. Our data also demonstrated that the expression of many genes related to Golgi structural integrity and function was significantly modified in senescent cells, suggesting a relationship between Golgi apparatus function and ageing.  相似文献   
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The purpose of this study was to determine the in vitro susceptibility to cetyltrimethylammonium naproxenate for various aerobic and anaerobic micro-organisms responsible for oral and pharyngeal diseases by assessing the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) or minimum fungicidal concentrations (MFCs) and by determining kill-times. The MICs of cetyltrimethylammonium naproxenate for 46 tested strains (25 reference strains and 21 clinical isolates) ranged from 8 to 500 micrograms/ml. The MIC was found to be 31.25 micrograms/ml for 36% of the reference strains. Even lower MIC values (15.63 micrograms/ml) were observed for some anaerobic strains, for Haemophilus influenzae and for Candida tropicalis. MIC and MBC values corresponded for the majority of strains tested while the MFC for C. tropicalis and C. albicans was much higher. Only 9.5% of the clinical isolates gave a MIC value of 31.25 micrograms/ml. Enterococcus faecalis, Streptococcus pyogenes and Staphylococcus aureus showed MIC at 62.5 micrograms/ml. The MIC and MBC values among the isolates were comparable, while the MFC value for the yeasts was greater. A concentration of 125 micrograms/ml of cetyltrimethylammonium naproxenate inhibited the growth of all bacteria, except Enterobacteriaceae and Pseudomonaceae, and yeasts. Cetyltrimethylammonium naproxenate shows very rapid kill-time for S. sanguis (0"), and rapid (15") for S. pyogenes, S. dysgalactiae and S. mutans and for Moraxella catarrhalis, while a longer kill-time was necessary for the other microbes tested.  相似文献   
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BACKGROUND: The aim of this study was to report on the prevalence of Actinobacillus actinomycetemcomitans (Aa) and the periodontal clinical conditions in children and adolescents from a rural area of central Italy compared with the ones from an urban area of the same region. METHOD: The study population consisted of 780 systemically healthy children, aged 6-14 years inhabiting the county of Chieti. 505 children attended 3 primary and 2 secondary schools from a rural area whereas 275 individuals attended 1 primary and 1 secondary school from the city of Chieti. The 2 provincial areas present a great difference in socioeconomic level and cultural background. Clinical examination consisted of recording the % of gingival sites positive for the presence of plaque (P1+), bleeding on probing (BOP+), mean probing depth (PD) from each primary or permanent tooth fully erupted in the oral cavity. Loss of periodontal attachment (AL+) was evaluated only in interproximal sites. AL+ subjects were distinguished in juvenile periodontitis (JP) prepubertal periodontis and early periodontitis (EP) patients. 8 gingival sites were microbiologically sampled in each subject and cultured, after pooling, for the presence of Aa. RESULTS: 30.3% of rural subjects, were positive for the presence of Aa, the difference from urban children (16%) being statistically significant (p=0.01) irrespective of gender and age. Aa showed a significantly (p=0.006) higher mean proportion in subgingival plaque samples from rural children (0.13% versus 0.02%). Loss of periodontal attachment in at least one site was found in 18 rural children (3.56%) (3 JP; 15 EP) and 2 urban girls (0.72%)(1 JP; 1 EP). No significant differences for AL were observed within the rural group according to the gender and age differentiation. In the urban group, both AL+ subjects were Aa+, while among children from rural areas all 3 JP and 13 EP subjects were Aa+. Rural subjects evidenced significantly worse clinical parameters with respect to urban children (% PI+ sites: p=0.000; % BOP+ sites: p=0.010; mean PD: p=0.000.) The relative risk for AL+ sites was significantly greater (2.42) in rural subjects harboring Aa in subgingival plaque. Similarly, the presence of Aa in subgingival plaque was related to a greater risk of more than 50% of BOP+ gingival sites in both rural and urban subjects (1.45 and 8.40, respectively). CONCLUSIONS: Results of this study suggest that Aa colonization in children and adolescents from central Italy is affected by socioeconomic and cultural factors; these factors also affect the periodontal condition of the subjects.  相似文献   
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