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Abstract Background To evaluate the expression and differential significance of c-Jun, p73, Casp-9 and N-ras in thymic epithelial tumors (TETs) with the aim to provide useful information for tumor biology and prospective therapy. Methods In this study, we analyzed the expression of four chromosome 1-related genes, namely c-Jun, p73, Casp-9 and N-ras, in 60 cases of thymic epithelial tumors. The tumors included 52 thymomas and 8 thymic carcinomas which were categorized according to the current WHO classification systems. Results Compared with the normal thymus tissue, all thymic epithelial tumors demonstrated higher expression of c-Jun and p73. The expression of c-Jun and p73 in type B2, B3 thymoma and thymic carcinomas was similar, and significantly higher than that in all other subtypes of thymomas. Unlike type A thymoma, the expression of Casp-9 was relatively lower in type B thymoma and thymic carcinomas. With respect to the clinical staging systems, c-Jun was more expressed in progressive tumors harboring higher stages. In contrast to c-Jun, p73 and Casp-9, there was no significant aberration with N-ras expression irrespective of either tissue or tumor types. Conclusions The overexpression of c-Jun, p73 and Casp-9 in thymic epithelial tumors is closely related with the pathogenesis and biological behavior of the neoplasms. These candidate biomarkers provided useful information for prospective personalized therapy in the clinical management. Additional non-English language abstract language: Chinese 背景:评估c-Jun, p73, Casp-9 和 N-ras在胸腺上皮性肿瘤诊断和鉴别诊断中的运用. 方法:根据世界卫生组织最新的诊断标准60例胸腺上皮性肿瘤分类,运用Envision法检测c-Jun,p73,Casp-9 和N-ras在不同亚型肿瘤中的表达情况,并结合临床病理学特征进行分析. 结果:c-Jun和p73在肿瘤中的表达明显高于正常胸腺组织;c-Jun和p73在B3,B2型胸腺瘤和胸腺癌的表达类似,且表达明显高于其他类型的胸腺肿瘤;Caspase-9在B型胸腺瘤和胸腺癌中的表达相对低于A型胸腺瘤;c-Jun的表达更常见于高级别的胸腺肿瘤. 结论:c-Jun,p73和Casp-9在胸腺肿瘤中的表达很好地反映了肿瘤的生物学特点,为胸腺肿瘤的诊断和鉴别诊断提供了较好的理论基础. Virtual Slides http://www.diagnosticpathology.diagnomx.eu/vs/1521774814749726

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers. In this study, our objective was to identify differentially regulated proteins in ESCC using isobaric tag for relative and absolute quantification (iTRAQ) technique and liquid chromatography-tandem mass spectrometry (LC-MS/MS). We compared the protein expression profiles of ESCC tumor tissues with the corresponding adjacent normal tissue from three patients. It was determined that 72 and 57 unique proteins were significantly up-regulated and down-regulated in all three samples. In addition, there were 431 significantly differentially regulated proteins having at least two biological samples. This subject found some of the differential proteins, such as prolyl 4-hydroxylase subunit alpha-1, prolyl 4-hydroxylase subunit alpha-2, and calponin-2, immunoglobulin superfamily containing leucine-rich repeat protein, and prolyl 3-hydroxylase1, which were few studies about them in ESCC. In order to determine the results, we performed another independent experiment. Our results indicated quantitative proteomics, as a robust discovery tool for the identification, differentially regulated proteins in cancers. [ABSTRACT FROM AUTHOR]

Background: The mTOR gene regulates cell growth by controlling mRNA translation, ribosome biogenesis, autophagy, and metabolism. Abnormally increased expression of mTOR was associated with carcinogenesis, and its functional single nucleotide polymorphisms (SNPs) may regulate the expression of mTOR and thus contribute to cancer risk. Methodology/Principal Findings: In a hospital-based case-control study of 1004 prostate cancer (PCa) cases and 1051 cancer-free controls, we genotyped six potentially functional SNPs of mTOR (rs2536 T>C, rs1883965 G>A, rs1034528 G>C, rs17036508 T>C, rs3806317 A>G, and rs2295080 T>G) and assessed their associations with risk of PCa by using logistic regression analysis. Conclusions/Significances: In the single-locus analysis, we found a significantly increased risk of PCa associated with mTOR rs2536 CT/CC and rs1034528 CG/CC genotypes [adjusted OR = 1.42 (1.13–1.78), P = 0.003 and 1.29 (1.07–1.55), P = 0.007), respectively], compared with their common homozygous genotypes, whereas mTOR rs2295080 GT/GG genotypes were associated with a decreased risk of PCa [adjusted OR = 0.76 (0.64–0.92), P = 0.003], compared with wild-type TT genotypes. In the combined analysis of the six SNPs, we found that individuals carrying two or more adverse genotypes had an increased risk of PCa [adjusted OR = 1.24 (1.04–1.47), P = 0.016], compared with individuals carrying less than two adverse genotypes. In the multiple dimension reduction analysis, body mass index (BMI) was the best one-factor model with the highest CVC (100%) and the lowest prediction error (42.7%) among all seven factors. The model including an interaction among BMI, rs17036508, and rs2536 was the best three-factor model with the highest CVC (100%) and the lowest prediction error of 41.9%. These findings suggested that mTOR SNPs may contribute to the risk of PCa in Eastern Chinese men, but the effect was weak and needs further validation by larger population-based studies. [ABSTRACT FROM AUTHOR]

Genetic variants of nucleotide excision repair (NER) genes have been extensively investigated for their roles in the development of prostate cancer (PCa); however, the published results have been inconsistent. In a hospital-based case-control study of 1,004 PCa cases and 1,055 cancer-free controls, we genotyped eight potentially functional single nucleotide polymorphisms (SNPs) of NER genes (i.e., XPC, rs2228001 T>G and rs1870134 G>C; XPD, rs13181 T>G and rs238406 G>T; XPG, rs1047768 T>C, rs751402 C>T, and rs17655 G>C; and XPF, rs2276464 G>C) and assessed their associations with risk of PCa by using logistic regression analysis. Among these eight SNPs investigated, only XPC rs1870134 CG/CC variant genotypes were associated with a decreased risk of prostate cancer under a dominant genetic model (adjusted odds ratio [OR] = 0.77, 95% confidence interval [CI] = 0.64-1.91, P = 0.003). Phenotype-genotype analysis also suggested that the XPC rs1870134 CG/CC variant genotypes were associated with significantly decreased expression levels of XPC mRNA in a mix population of different ethnicities. These findings suggested that XPC SNPs may contribute to risk of PCa in Eastern Chinese men.

The purpose of this study was to investigate the relation between expression of Wnt11, Rho-associated protein kinase 2 (Rock2), and its clinical characteristics in esophageal squamous cell carcinoma (ESCC). Expression of Wnt11 and Rock2 protein was examined by using immunohistochemistry that contained 260 paraffin-embedded specimens of ESCC and its adjacent normal tissues; expression of Wnt11 and Rock2 protein was verified by Western-blotting that contained 20 specimens of ESCC and its adjacent normal tissues. The positive rates of Wnt11 protein in normal esophageal epithelium tissue was 29.8% and in esophageal carcinomas tissue was 31.9%; there was no significant difference between the two groups(P>0.05); The positive rates of Rock2 protein in normal esophageal epithelium tissue was 12.3% and in esophageal carcinomas tissues was 56.5%, there was a significant difference between the two groups (p<0.05). The expression of Rock2 protein was significantly related with the invasion of vascular and there was no significantly difference between the expression of Rock2 protein and ESCC patients' tumor location, differentiation, T stage, and lymph node metastases. The abnormal expression of Rock2 protein may promote tumor cell invasion., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers. In this study, our objective was to identify differentially regulated proteins in ESCC using isobaric tag for relative and absolute quantification (iTRAQ) technique and liquid chromatography-tandem mass spectrometry (LC-MS/MS). We compared the protein expression profiles of ESCC tumor tissues with the corresponding adjacent normal tissue from three patients. It was determined that 72 and 57 unique proteins were significantly up-regulated and down-regulated in all three samples. In addition, there were 431 significantly differentially regulated proteins having at least two biological samples. This subject found some of the differential proteins, such as prolyl 4-hydroxylase subunit alpha-1, prolyl 4-hydroxylase subunit alpha-2, and calponin-2, immunoglobulin superfamily containing leucine-rich repeat protein, and prolyl 3-hydroxylase1, which were few studies about them in ESCC. In order to determine the results, we performed another independent experiment. Our results indicated quantitative proteomics, as a robust discovery tool for the identification, differentially regulated proteins in cancers.

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most malignancies with a very poor outcome in China. Wnt11 and Rock2, new identified proteins highly associated with metastasis of many cancers, which were never reported in esophageal squamous cell carcinoma (ESCC). Here we measured the expression levels of Wnt11 and Rock2 in tissues from 265 patients with ESCC. Immunohistochemical staining was employed to detect the correlation of Wnt11 and Rock2 expression with clinicopathological features., Methods: The expression of Wnt11 and Rock2 was detected by immunohistochemistry in esophageal squamous cell carcinomas and normal esophageal tissues. A chi-square test was used to assess the statistical significance of the correlations between Wnt11, Rock2 expression and different clinicopathological parameters, respectively., Results: The high-expression of Wnt11 and Rock2 was observed in ESCCs. Seventy-five cases of ESCC (51.7%) showed a positive expression of Wnt11, which indicated a significant association with the AJCC stage (P=0.007). Ninety-eight cases of ESCC (65.5%) showed a positive expression of Rock2, which indicated a significant association with ethnic background. There were no close correlations between Rock2 expression and gender, tumor location, AJCC stage, lymph node metastasis. Specifically, the expression of Rock2 was significantly different between Hans and Kazaks ethnicities (P=0.000). In Kaplan-Meier curve analysis, no significant correlation was observed between the expression of Wnt11, Rock-2 and the poor prognosis of ESCCs., Conclusion: Our finding suggests that the over-expression of Rock2 may play an important role in the carcinogenesis and progression, and may become a new underlying molecular marker in the diagnosis and treatment in ESCC.

Background: Extranodal nasal-type NK/T-cell lymphoma (ENKTCL) is a common and geographic predominant disease in China. We observed the clinical and pathologic features of this tumor type and its relationship to Epstein-Barr virus (EBV), and focused on the epidermology and prevalence of ENKTCL in Xinjiang, in order to improve the diagnostic and differential diagnosis ability., Methods: 103 cases with nasal-type NK/T-cell lymphoma were recruited and assessed. All cases were submitted for histological assessment, immunophenotyping, in situ hybridization detection of EBV-encoded RNA (EBER), and clinical information analysis., Results: Male patients, aged between 40 and 50 years, were predominantly of Han ethnicity outnumbering those of Uyghur ethnicity. 80 cases of ENKTCL involved the nasal cavity or other areas of the upper respirodigestive tract whereas the remaining ones involved other extranodal sites. All cases exhibited similar histological changes: necrosis and inflammatory infiltration were frequently present. Cytologic atypical as well as angiocentric and angiodestructive growth patterns of the tumor cells were consistently noted, although the sizes and contours of the tumor cells varied considerably. All cases expressed one or several T-cell markers and at least one cytotoxic molecule. 86 cases (84%) expressed CD56, and 97 cases submitted for EBER detection showed positive results. ENKTCL affects predominantly middle-aged Han Chinese in the Xinjiang region, with a predilection to involvement of the nasal cavity and a strong association with a high EBV load., Conclusions: Early and correct identification of the disease in daily practice depends on the combination of morphologic evaluation, immunophenotypic assessment, and EBER detection.

Objective: To explore the mechanism underlying changes in microvascular reactivity in single- and double-transgenic mice., Methods: Peripheral vascular reactivity to the vasodilators, acetylcholine and sodium nitroprusside, on perfused microvasculature of the hind footpad was investigated using nontransgenic mice, single-transgenic mice expressing the human APP-C100 (TgC100. WT or TgC100. V717F) and double-transgenic mice coexpressing human APP-C100 and human SOD(1) (G93A) genes., Results: Single TgC100 and double Tg mice C100/SOD(1) (G93A) at 2 - 3 months old showed a statistical decrease of 28% in blood flux compared to nontransgenic control mice. In addition, vasodilative responsiveness was markedly reduced to 34% in 8 - 9 months old TgC100 mice compared to control mice. There was no significant difference in the profile of vasodilative reaction between TgC100. WT and TgC100. V717F mice. TgC100 and double Tg mice also had higher levels of A beta peptide in plasma than nontransgenic mice (P < 0.01)., Conclusions: The present study suggests that the altered reactivity of the microvasculature may be mediated by circulating soluble A beta peptides. The mechanisms underlying the vasoactivity of circulating A beta in TgC100 and double Tg mice may involve both the endothelium and nonendothelium.