Identification of Novel Methylation Markers in Hepatocellular Carcinoma using a Methylation Array

Promoter CpG island hypermethylation has become recognized as an important mechanism for inactivating tumor suppressor genes or tumor-related genes in human cancers of various tissues. Gene inactivation in association with promoter CpG island hypermethylation has been reported to be four times more frequent than genetic changes in human colorectal cancers. Hepatocellular carcinoma is also one of the human cancer types in which aberrant promoter CpG island hypermethylation is frequently found. However, the number of genes identified to date as hypermethylated for hepatocellular carcinoma (HCC) is fewer than that for colorectal cancer or gastric cancer, which can be attributed to fewer attempts to perform genome-wide methylation profiling for HCC. In the present study, we used bead-array technology and coupled methylation-specific PCR to identify new genes showing cancer-specific methylation in HCC. Twenty-four new genes have been identified as hypermethylated at their promoter CpG island loci in a cancer-specific manner. Of these, TNFRSF10C, HOXA9, NPY, and IRF5 were frequently hypermethylated in hepatocellular carcinoma tissue samples and their methylation was found to be closely associated with inactivation of gene expression. Further study will be required to elucidate the clinicopathological implications of these newly found DNA methylation markers in hepatocellular carcinoma.     

两类远岛环境对守岛战士社会适应能力的影响

响比对照组明显,建议对远岛长期守卫战士进行系统的社会适应能力训练.     

Prominent binding of the dopamine D3 agonist [H]PD 128907 in the caudate–putamen of the adult rat

We have analyzed the binding properties of the selective D₃ receptor agonist [³H]PD 128907 in 120 days old rats. In tissue sections, we found high numbers of binding sites for [³H]PD 128907 both in the islands of Calleja and the caudate–putamen (B_max values being 500 and 1000 fmol/mg protein, respectively). The K_D values were higher in the caudate–putamen than in the islands of Calleja. Similar regional differences in B_max and K_D values were observed in membranes from the caudate–putamen and the subcortical limbic region. The distribution of [³H]PD 128907 in adult rats is markedly different from that observed in young rats. Taken together, the present results suggest a prominent presence of D₃ receptors in the caudate–putamen of adult, but not young, rats. Hence, these findings may have important physiological, pathophysiological, and clinical implications.     

Carcinoma basocelular en el Área Sur de Salud de Tenerife. Características clínico-patológicas fundamentales y estado de los bordes tras exéresis

Background and objectiveSurgical excision is the treatment of choice for basal cell carcinoma (BCC). Complete excision with clear margins is important for reducing the risk of recurrence. The aims of this study were to describe the characteristics of BCCs in our health care area, calculate the percentage of positive margins after surgical excision, and determine the risk factors for incomplete excision.Material and methodsRetrospective observational study of BCCs that were surgically removed at Hospital Universitario Nuestra Señora de Candelaria, in Santa Cruz de Tenerife, Spain, between January 1, 2014 and December 31, 2014. Information was collected on demographic, clinical, and histologic variables, surgical approach, margin status, and the department responsible.ResultsIn total, 966 BCCs were diagnosed in 776 patients. Nine percent of tumors with complete data were biopsied, 89% were surgically excised, and 2% were removed by shave excision. The median age of patients with excised tumors was 71 years and 52% were men. BCCs were most often located on the face (59.1%). Surgical margins were analyzed in 506 cases, 17% of which had positive margins. Incomplete excision was significantly more common in tumors located on the face (22% vs. 10% for other locations) and in high-risk subtypes according to the World Health Organization classification (25% vs. 15% for low-risk subtypes).ConclusionsThe characteristics of BCCs in our health care area are similar to those described elsewhere. Facial location and histologic subtype are risk factors for incomplete excision. Careful surgical planning is therefore important in the initial management of BCCs with these characteristics.     

Ciguatoxin Detection in Flesh and Liver of Relevant Fish Species from the Canary Islands

The Canary Islands are a ciguatoxin (CTX) hotspot with an established official monitoring for the detection of CTX in fish flesh from the authorised points of first sale. Fish caught by recreational fishermen are not officially tested and the consumption of toxic viscera or flesh could lead to ciguatera poisoning (CP). The objectives of this study were to determine the presence of CTX-like toxicity in relevant species from this archipelago, compare CTX levels in liver and flesh and examine possible factors involved in their toxicity. Sixty amberjack (Seriola spp.), 27 dusky grouper (Epinephelus marginatus), 11 black moray eels (Muraena helena) and 11 common two-banded seabream (Diplodus vulgaris) were analysed by cell-based assay (CBA) and Caribbean ciguatoxin-1 (C-CTX1) was detected by liquid chromatography mass spectrometry (LC-MS/MS) in all these species. Most of the liver displayed higher CTX levels than flesh and even individuals without detectable CTX in flesh exhibited hepatic toxicity. Black moray eels stand out for the large difference between CTX concentration in both tissues. None of the specimens with non-toxic liver showed toxicity in flesh. This is the first evidence of the presence of C-CTX1 in the common two-banded seabream and the first report of toxicity comparison between liver and muscle from relevant fish species captured in the Canary Islands.     

Serum C3 and C4 levels and complement-dependent antibody-mediated cytotoxic activity of islet cell surface antibody in Type 1 (insulin-dependent) diabetic children

Summary The role of complement in the pathogenesis of diabetes was studied in 31 Type 1 (insulin-dependent) diabetic children by assaying serum islet cell surface antibody, C₃, C₄ and serum complement-dependent antibody-mediated cytotoxicity. Nine of 21 islet cell surface antibody-positive children were within 5 months of disease onset and showed significantly lower serum C₃ and C₄ levels than either 1 year later or the remainder of the islet cell surface antibody-positive children at 6–12 months after disease onset. The overall trend of all islet cell surface antibody-positive diabetic children within 1 year of disease onset was toward increased serum C₃ and C₄ levels as the disease progressed. Serum C₄ concentration and complement-dependent antibody-mediated cytotoxicity which showed an initial negative correlation were uncorrelated 1 year later. Four children who were initially strongly islet cell surface antibody-positive but negative 1 year later also exhibited significantly higher (p<0.05) mean serum C₄levels after 1 year. There was a significant decrease in complement-dependent antibody-mediated cytotoxicity when sera from the diabetic children were treated with either ethylene glycol tetra-acetic acid or ethylene diamine tetra-acetic acid. These data strongly suggest that complement-dependent antibody-mediated cytotoxicity induced by the classical complement pathway involving an islet cell surface antibody may play an important role in the pathogenesis of Type 1 diabetes.