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Background The protein anillin (ANLN) has important roles in cell cytokinesis. Until now, no studies have evaluated the role of ANLN expression in a large cohort of patients with urothelial carcinoma of the upper urinary tract (UCUT). Methods This study analysed 156 cases of primary localised UCUT. Pathological slides were reviewed and clinical findings were collected. An immunohistochemical study was performed and the cytoplasmic and nuclear staining results of UCUT were recorded. Expressions of ANLN were analysed to identify correlations with various clinicopathological parameters, disease-specific survival (DSS) and metastasis-free survival (MeFS). Results Overexpression of ANLN in the nucleus had significant positive associations with tumour stage (p=0.017), histological grade ( p=0.040), mitotic count (p=0.023), tumour necrosis ( p=0.009), invasion patterns (p<0.001) and simultaneous involvement of the renal pelvis and ureter (p=0.032). Overexpression of ANLN in the cytoplasm had a significant negative correlation with patient age (p=0.004), tumour grade (p=0.021) and vascular invasion (p=0.013). Notably, univariable analysis showed that overexpression of ANLN in the nucleus was significantly associated with a poor DSS ( p=0.006) and MeFS ( p=0.010), and multivariable analysis showed that it was an independent predictor of adverse DSS outcome ( p=0.031, relative risk 1.535). Low expression of ANLN in the cytoplasm was strongly associated with a poor DSS ( p=0.045) and MeFS (p=0.041) in univariable analysis but not in Cox regression analysis. Conclusions Subcellular localisation of ANLN is correlated with different tumour phenotypes and probably confers different tumorigenicity. Since high nuclear expression of ANLN is also an independent predictor of poor DSS, it is a useful prognostic marker of UCUT. [ABSTRACT FROM AUTHOR]

Background. Central neurocytoma and oligodendroglioma are rare tumors of the central nervous system. However, diagnosis between these two types of tumors is challenging due to their many cytological and histological similarities. Death-associated protein kinase (DAPK) is a calcium/calmodulin-regulated serine/threonine protein kinase involved in many apoptosis pathways, and repressed expression of DAPK by promoter hypermethylation has been found in a variety of human cancers.The purpose of this study was to assess DAPK protein expression and promoter hypermethylation in central neurocytoma and oligodendroglioma. Method. Central neurocytoma and oligodendroglioma samples were obtained from age- and sex-matched patients. DAPK protein expression was performed using immunohistochemical assays in formalin-fixed, paraffin-embedded sections. DAPK promoter hypermethylation was carried out using bisulfite-modified genomic DNA in methylation-specific PCR followed by separation in agarose gels. Findings. A statistically significant difference (P = 0.021) in DAPK promoter hypermethylation between central neurocytoma (76.9%) and oligodendroglioma (20%) was observed. High levels of DAPK protein expression were generally found in oligodendroglioma (90%), compared with 38.5% in central neurocytoma (P = 0.054; not statistically significant). There was an inverse correlation between DAPK protein expression and DAPK promoter hypermethylation in the cohort of 23 patients (P = 0.002). Conclusions. The results show that DAPK promoter hypermethylation and repressed expression of DAPK protein were more common in central neurocytoma than in oligodendroglioma.Thus, DAPK promoter hypermethylation could be useful for differential diagnosis between these two types of tumors, whereas DAPK protein expression might be less predictive.The role of DAPK promoter hypermethylation in the pathogenesis of central neurocytoma warrants further study. [ABSTRACT FROM AUTHOR]

Cholesteatoma is a destructive and expanding growth of keratinizing squamous epithelium in the middle ear or petrous apex. The molecular and cellular processes of the pathogenesis of acquired middle ear cholesteatoma have not been fully understood. In this study, comparative proteomic analysis was conducted to investigate the roles of specific proteins in the pathways regarding keratinocyte proliferation in cholesteatoma. The differential proteins were detected by comparing the two-dimension electrophoresis (2-DE) maps of the epithelial tissues of 12 attic cholesteatomas with those of retroauricular skins. There were 14 upregulated proteins in the epithelial tissues of cholesteatoma in comparison with retroauricular skin. The modulation of five crucial proteins, HSP27, PRDX2, GRP75, GRP78 and GRP94, was further determined by RT-PCR, Western blot and immunohistochemistry. Phosphorylation of HSP27 at Ser-82 was identified by mass spectroscopy. The results of this study suggested that phosphorylated HSP27 is the end expression of two potential signal-transduction pathways, and together with PRDX2, they are very likely involved in the proliferation of keratinocytes in cholesteatoma. Upregulations of GRP75, GRP78 and GRP94 in keratinocytes may be able to counter endoplasmic reticulum stress, to inhibit cell apoptosis, to prevent protein unfolding and to promote cholesteatoma growth. [ABSTRACT FROM AUTHOR]

Administration of antioxidants and anti-inflammatory agents is an effective strategy for preventing ultraviolet (UV) irradiation-induced skin damage. Artocarpus communis possesses several pharmacological activities, such as antioxidant, anticancer and anti-inflammation. However, the photoprotective activity of methanol extract of A. communis heartwood (ACM) in ultraviolet irradiation-induced skin damage has not yet been investigated. The present study was performed using ultraviolet absorption, histopathological observation, antioxidant and anti-inflammation assays to elucidate the mechanism of the photoprotective activity of ACM. Our results indicated that ACM displayed a UVA and UVB absorption effect and then effectively decreased scaly skin, epidermis thickness and sunburn cells during ultraviolet irradiation in hairless mice. ACM not only decreased ultraviolet irradiation-mediated oxidative stress, including lowering the overproduction of reactive oxygen species and lipid peroxidation (p < 0.05), but also reduced the levels of pro-inflammatory cytokines, including tumor necrosis factor-a (TNF-a) and interleukin 1ß. Additionally, ACM can decrease the synthesis of cytosolic phospholipase A2, cyclooxygenase, inducible nitric oxide synthase and vascular cell adhesion molecular-1 via inhibiting TNF-a-independent pathways (p < 0.05) in UVB-mediated inflammation and formation of sunburn cells. Consequently, we concluded that ACM extract has a photoprotective effect against UVB-induced oxidative stress and inflammation due to its sunscreen property, and its topical formulations may be developed as therapeutic and/or cosmetic products in further studies. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (DM), characterized by peripheral insulin resistance, is the most common form of diabetes. Probiotics are live micro-organisms that, when administered in adequate amounts, confer delaying effect on DM development. In this study, the effects Lactobacillus reuteri GMNL-263 (Lr263), a new probiotic strain developed by our laboratory, on insulin resistance and the development of hepatic steatosis in high-fructose fed rats were explored. Furthermore, the relevant regulatory pathways involved were also investigated. Method: Male Sprague-Dawley rats were fed a high-fructose diet with or without Lr263 administration for 14 weeks. The composition of fecal microbiota, oral glucose tolerance, glycated haemoglobin, insulin, leptin, C-peptide, and incretions were measured. The markers of liver injury, serum and hepatic lipids profile, activity of hepatic antioxidant enzyme, and proinflammatory cytokines in adipose tissue were investigated. Additionally, the expression of hepatic lipogenic genes and insulin signaling related genes in adipose tissue were also studied. Liver sections were examined for hepatic steatosis using hematoxylin-eosin staining. Results: The levels of serum glucose, insulin, leptin, C-peptide, glycated hemoglobin, GLP-1, liver injury markers, lipid profile in serum and liver were significantly increased in high-fructose-fed rats. However, after Lr263 administration, the elevation of these parameters was significantly suppressed. Feeding of Lr263 reversed the decreased number of bifidobacterium species and lactobacillus species and increased number of clostridium species induced by high fructose treatment. The decreased activities of hepatic antioxidant enzymes in HFD rats were dramatically reversed by Lr263 treatment. Concentrations of IL-6 and TNF-α in adipose tissue which were elevated in high fructose treatment were markedly decreased after Lr263 feeding. Decreased levels of PPAR- γ and GLUT4 mRNA after high fructose treatment were significantly enhanced by Lr263 administration. Lr263 consumption normalized the increased lipogenic gene (Srebp-1c, FAS, and Elvol6) expressions stimulated by high fructose. Administration of Lr263 significantly ameliorated hepatic steatosis observed in high fructose treated rats. Conclusion: Our study provided evidences clarifying the effectiveness of Lr263 on reducing insulin resistance as well as hepatic steatosis formation in high-fructose-fed rats and suggested that Lr263 may be a promising therapeutic agent in treating type 2 diabetes. [ABSTRACT FROM AUTHOR]

This study examines whether the expression of cyclooxgenase-2 (COX-2) in urothelial carcinoma (UC) is associated with macrophage infiltration, hypoxia-inducible factor-1α (HIF-1α) expression and angiogenesis. We investigated the expression of COX-2 associated with HIF-1α and performed double immunohistochemical analysis of 216 UCs for COX-2 expression and the correlation with tumor-associated-macrophage (TAM) density and microvessel density (MVD) in situ. A high expression of COX-2 was positively correlated with tumor invasiveness, histologic grade and HIF-1α expression in UC (p<0.0001, p=0.003, p<0.0001, respectively). Quantification of double staining of COX-2/CD34 and COX-2/CD68 showed that a higher MVD and TAM density was found in COX-2 high-expression than in COX-2 low-expression tumor fields (p<0.0001). Adjacent to the principal of COX-2 expression areas, MVD value and TAM density were significantly increased in HIF-1α high-expression specimens compared with HIF-1α low-expression ones (p<0.0001). Interestingly, our data revealed that high COX-2 expression (p =0.002), high HIF-1α expression (p<0.0001) and TAM density (p<0.0001) were all associated with high MVD value. Our results suggest that COX-2 may produce a cooperative effect in promoting tumor progression and may be involved in the process of angiogenesis through increasing TAM infiltration or HIF-1α regulation by hypoxia. [ABSTRACT FROM AUTHOR]

The aim was to investigate the expression of human telomerase reverse transcriptase (hTERT) and cyclin D1 in correlation with clinicopathologic features of urothelial carcinoma (UC). Tissue microarrays (TMA) were constructed from paraffin-embedded specimens of 94 UC patients and immunohistochemical staining was used. High hTERT expression was found in 50 (53%) of the 94 tumors and was significantly associated with tumor invasiveness and tumor grade ( P=0.008 and 0.0190, respectively). High cyclin D1 expression was found in 69 (73%) of the 94 tumors and was significantly associated with non-invasiveness and smaller tumor size, but there was no correlation with tumor grade. Kaplan–Meier analysis indicated that patients with low hTERT and high cyclin D1 levels had longer local recurrence-free survival ( P=0.0482 and 0.0123, respectively). In addition, patients with high cyclin D1 levels had longer disease-free survival ( P=0.0195). In conclusion, this study demonstrated that hTERT and cyclin D1 may be of recurrence predictive value for UC, thus providing clinicians with ancillary information when deciding on suitable therapeutic strategies in UC. [ABSTRACT FROM AUTHOR]

The aim of our study was to analyze the expression and possible role of CD66a in colorectal adenoma and adenocarcinoma and the relationship between its expression and pre-operation serum carcinoembryonic antigen (CEA) level and tumor stage in patients with colorectal adenocarcinomas. Paraffin-embedded sections from 184 patients including 42 colorectal adenomas with low-grade dysplasia, 43 adenomas with high-grade dysplasia, and 99 adenocarcinomas were collected for this study. Immunohistochemical analysis was performed, and the expression and the location of CD66a were evaluated and were correlated with β-catenin nuclear expression. The expression of CD66a was found not only in the apical membrane of neoplastic glands but also in secretion within the lumen of the neoplastic glands including adenomas and adenocarcinomas. Expressions of secreted CD66a were of higher level in adenocarcinoma than in adenoma with high-grade dysplasia and adenoma with low-grade dysplasia ( p < 0.0001). High expression of secreted CD66a was also associated with tumor stage, invasion, and pre-operation serum CEA level of patients with colorectal adenocarcinoma. This study implied that CD66a can function both as an epithelial cell adhesion protein or alternatively as secreted CD66a. In addition, a high expression of CD66a was significantly correlated with tumor invasion, stage, and pre-operation serum CEA level. [ABSTRACT FROM AUTHOR]

The clinical pathologic criteria for nuclear features of papillary thyroid carcinoma are subjective and sometimes cannot distinguish carcinoma from adenomatous goiter and follicular neoplasms. No single antibody has demonstrated high sensitivity or specificity in making these distinctions. Using quantitative analysis of immunohistochemical staining with D2-40, a recently available monoclonal antibody used as a lymphatic endothelial marker, we examined 72 cases of papillary carcinoma. Controls included 36 follicular adenomas, 36 follicular carcinomas, and 20 adenomatous goiters with papillary hyperplasia. Cytoplasmic D2-40 immunoreactivity was present in 60 of 72 papillary carcinomas, 2 cases of follicular adenoma and 2 cases of follicular carcinoma, whereas no adenomatous goiter or normal thyroid glands contained positive epithelial cells. Overexpression of D2-40 in papillary thyroid carcinomas thus has potential diagnostic utility in differentiating these tumors from their potential histologic mimics. [ABSTRACT FROM AUTHOR]

Olfactory neuroblastoma is an uncommon neoplasm. Typically, these tumors are indolent with long-standing symptomatology, but the fact that the lesions are indeed malignant has been proven by the repeated demonstration that they can metastasize to distant organs. Suitable prognostic factors are lacking and therapeutic strategy still remains controversial. Expression of human telomerase reverse transcriptase (hTERT) is associated with most human malignancies and high levels have been correlated with poor prognosis in many cancers. In comparison, overexpression of cyclin-D1 occurs in several malignancies and has been associated with aggressive tumor behavior and poorer prognosis. In this study, we collected 16 olfactory neuroblastomas from the Kaohsiung Medical University Hospital. The aim was to investigate the value of immunoexpression of hTERT and cyclin-D1 in correlation with clinicopathologic features of olfactory neuroblastoma. Low and high cyclin-D1 expression was found in 6 and 10 cases, respectively. For hTERT, low and high protein expression was detected in 5 and 11 tumors, respectively. Cyclin-D1 expression was not correlated with selected parameters. However, high hTERT expression was significantly correlated with high Kadish stage. In conclusion, high hTERT expression can be considered a potential indicator of aggressive olfactory neuroblastoma. [ABSTRACT FROM AUTHOR]

The article presents a study which proposes a membrane for selective capture of the microbial pathogen Listeria monocytogenes. The methodology of the study is detailed. Based on results, fluorescent microscopy from batch experiments show that L. monocytogenes attaches nonspecifically to poly-L-lysine/glutaraldehyde membranes and is not removed by washing with protein-based surfactants buffer.

Arsenic is widely distributed in the environment, and is a proven toxic and carcinogenic agent that is associated with various human malignancies, including bladder cancer. However, the mechanisms of its carcinogenic action are still not well understood. In addition, over-expression of mutant p53 and cyclooxygenase-2 (COX-2) frequently occurs in a variety of human malignancies. It is therefore of interest to study the genotoxicity of arsenic salts on human uroepithelial cells and the expression of oncoproteins p53 and COX-2. In this study, the relative genotoxicity of sodium arsenite was evaluated in SV-40 immortalized human uroepithelial cells (SV-HUC-1) using the alkaline comet assay. The expression of mutant p53 and COX-2 was also evaluated by immunocytochemistry and western blotting. Our results revealed that sodium arsenite was able to induce DNA damage, and that its genotoxicity is correlated with its concentration. In addition, the expression of mutant p53 increased in parallel with comet scores, and the maximal expression of mutant p53 was observed at 4 μM arsenite. Similarly, sodium arsenite stimulated a concentration-dependent increase in COX-2 expression. In conclusion, this study demonstrated that sodium arsenite is genotoxic to uroepithelial cells in vitro, and that it will induce expression of mutant p53 and COX-2 proteins, indicating a possible key event in carcinogenesis. This study provides us with knowledge of the relationship between p53 and COX-2 over-expression in arsenite-treated urothelial cells and suggests a potential therapeutic role of COX-2 inhibitors in human urothelial malignancies. [ABSTRACT FROM AUTHOR]