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Warthin tumor is a benign salivary gland tumor comprising ductal epithelium and lymphoid stroma. To date, reports about the malignant transformations of intraepithelial and lymphoid components in Warthin tumor are extremely rare; lymphoid malignant transformation into B-cell lymphoma is particularly rare in combination with T-cell lymphoma. The case of Warthin tumor complicated with T-lymphoblastic lymphoma is reported to emphasize the importance of a careful light microscopic evaluation of lymphoid tissue in Warthin tumor for identifying occult lymphoma presence, reducing misdiagnosis and missed diagnosis, and determining a timely treatment.Warthin瘤是一种良性唾液腺肿瘤，由导管上皮和淋巴样间质组成，迄今为止，有关Warthin瘤内淋巴成分恶变的报道罕见，且多恶变为B细胞淋巴瘤，合并T细胞淋巴瘤更尤为少见。本文报道1例Warthin瘤合并T淋巴母细胞淋巴瘤，旨在强调要对Warthin瘤内的淋巴组织进行仔细的光学显微镜评估，以识别隐匿性淋巴瘤的存在，减少误诊及漏诊并及时治疗。.

Long non-coding RNAs (lncRNAs) have a role in the occurrence and development of lung squamous cell carcinoma (LUSC). lncRNA γ-butyrobetaine hydroxylase 1 (BBOX1)-antisense 1 (AS1) may contribute to disease development. However, there are no studies on the role of BBOX1-AS1 in LUSC to date. In the present study, an in-house gene microarray analysis was performed to detect the differentially expressed lncRNAs and mRNAs between three pairs of LUSC and normal lung tissues. Only one lncRNA, BBOX1-AS1, was differentially expressed in the in-house microarray and The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and ArrayExpress databases. Reverse transcription-quantitative PCR (RT-qPCR) was then performed and the original RNA-sequencing data from the TCGA, GEO and ArrayExpress datasets were used to determine the expression and clinical value of BBOX1-AS1 in LUSC. In addition, a Cell Counting Kit-8 assay, cell cycle analysis and scratch assay were performed to explore whether BBOX1-AS1 expression affected the proliferation and migration of LUSC cells in vitro. The results of the RT-qPCR analysis and data obtained from the TCGA database, GEO datasets, in-house gene microarray and standard mean deviation analysis all supported the upregulated expression level of BBOX1-AS1 in LUSC. Furthermore, silencing of BBOX1-AS1 inhibited the proliferation and migration of LUSC cells according to in vitro assays. In addition, the cells were arrested in S-phase after knockdown of BBOX1-AS1. In conclusion, the expression level of BBOX1-AS1 was upregulated in LUSC tissues. BBOX1-AS1 may exert an oncogenic effect on LUSC by regulating various biological functions. However, additional functional experiments should be performed to verify the exact mechanism.

BACKGROUND: Cholangiocarcinoma (CCA), which consists of intrahepatic CCA (iCCA), perihilar CCA (pCCA), and distal CCA (dCCA), is an aggressive malignancy worldwide. PCCA and dCCA are often classified as extrahepatic CCA (exCCA). However, the differences in mutational characteristics between pCCA and dCCA remain unclear. METHODS: Deep sequencing targeting of 450 cancer genes was performed for genomic alteration detection. The tumor mutational burden (TMB) was measured by an algorithm developed in-house. Correlation analysis was conducted using Fisher’s exact test. RESULTS: FGFR2 and ERBB2 mutations mainly occurred in iCCA and exCCA, respectively. In exCCA, the frequencies of PIK3CA, FAT4, KDM6A, MDM2, and TCF7L2 mutations were significantly higher in pCCA compared to dCCA, while the frequencies of TP53 and KRAS mutations were markedly lower in pCCA than those in dCCA. The prognosis-related mutations were different among the CCA subtypes. NF1 mutation was associated with short disease-free survival (DFS) and overall survival (OS), and ERBB2 mutation was associated with short DFS in dCCA patients. Meanwhile, MAP2K4 mutation was associated with long DFS and OS, and TERT mutation was associated with short DFS in pCCA. A series of mutations in genes, including ARID1A, ARID2, SMAD4, TERT, TP53, and KRAS, were found to be associated with the TMB. CONCLUSIONS: In this study, we investigated the comprehensive genomic characterizations of CCA patients, identified the significant alterations in each subtype, and identified potential biomarkers for prognosis prediction. These results provide molecular evidence for the heterogeneity of CCA subtypes and evidence for further precision targeted therapy of CCA patients.

Objectives: The objective of the study is to provide an efficient and practical screening strategy to distinguish a broader spectrum of Lynch syndrome (LS) and LS mimics-associated colorectal cancer (CRC), including Lynch-like syndrome (LLS), constitutional mismatch repair-deficiency, familial CRC type X (FCCTX), and polymerase proofreading-associated polyposis syndrome. Materials and Methods: 1294 cases of CRC samples were detected mismatch repair (MMR) status using immunohistochemistry (IHC) staining, in which the cases with MLH1-deficient CRC underwent BRAF mutation analysis by IHC. Following the personal and/or family history survey, next-generation sequencing (NGS) was used to detect gene variants. Results: 1294 CRC patients were dichotomized into tumors caused by a deficient MMR (dMMR) system and a proficient MMR (pMMR) system after MMR status analysis. 45 patients with suspected sporadic dMMR CRC were then separated from MLH1-deficient CRC though BRAF mutation status analysis by IHC. Following the personal and/or family history survey for 1294 patients, as well as germline genetic testing by NGS, 34 patients were diagnosed as LS (8 cases), SLS (13 cases), LLS ( 6 cases), FCCTX (3 cases), and sporadic CRC (4 cases). Conclusions: Our screening strategy, which consists of clinical and molecular analyses, is expected to improve the screening efficiency and management for the LS and LS mimics.

Background Succinate dehydrogenase deficient gastrointestinal stromal tumors (SDH-deficient GISTs), which lack KIT or PDGFRA mutations demonstrate unique clinical and pathological features, and they respond poorly to standard targeted therapy. We herein present a novel case of SDH-deficient GIST in a three-month-old infant’s colon mesentery, and he is the youngest patientto date. Case presentation The infantpresented with complaints of blood in the stool. CT showed a 6.3 × 4.6 cm mass in the left lower retroperitoneal. Complete resection of tumor and segmental bowel resection was performed without regional lymphadenectomy. Histologically, tumor cells were distinctive in their multinodular colon wall involvement with interspersed tracts of colon wall smooth muscle. The tumor was composed mainly of epithelioid cells. Immunohistochemically, the tumor cells were positive for Vim, CD117, PDGFR, while negative for SDHB. Mutational analysis showed a synonymous mutation for SDHB and wild-type for KIT and PDGFRA. Two months after surgery, metastases were found and Imatinib was administered. Unfortunately, the disease continued to progress, and the infant died 5 months after surgery. Conclusions SDH-deficient GISTs comprise a subgroup of a relatively rare tumor type and show a number of clinically and biologically unique features, especially for infants. It is of great importance to developing new therapeutic targets and novel specific drugs.

X-inactivation-specific transcript (XIST) is a long noncoding RNA (lncRNA) that functions as an indicator of various human tumors, including those of breast cancer. This study was conducted to characterize a novel regulatory network involving XIST in breast cancer cells. The mRNAs of XIST, miR-125b-5p, and NOD-like receptor family CARD domain containing 5 (NLRC5) in breast cancer cells and tissues were analyzed using quantitative real-time polymerase chain reaction. Cell proliferation, apoptosis, migration, and invasion were separately detected via cell counting kit-8, flow cytometry, and Transwell assays. The relationships between XIST, miR-125b-5p, and NLRC5 were predicted and then confirmed using the dual-luciferase reporter assay. NLRC5 protein expression was quantitated using western blot assays. XIST was found to be overexpressed in breast cancer tissues and cells, which was accompanied by miR-125b-5p downregulation and NLRC5 upregulation. XIST knockdown significantly repressed cell proliferation, anti-apoptosis, migration, and invasion activities in breast cancer cells, and the loss of miR-125b-5p had a similar effect. XIST was shown to sponge miR-125b-5p, which in turn targeted NLRC5. NLRC5, a breast cancer promotor, is negatively regulated by miR-125b-5p. Moreover, the downregulation of NLRC5 induced by the loss of XIST was significantly reversed by miR-125b-5p knockdown. In conclusion, the lncRNA XIST promotes the malignancy of breast cancer cells partly by competitively binding to miR-125b-5p, which then led to increased NLRC5 expression. Our study suggests that targeting XIST may be a possible treatment for breast cancer.

Acetylene hydrochlorination is an important aspect of the industrial synthesis of polyvinyl chloride, but it requires a toxic mercury chloride catalyst. Here we report a green, highly efficient and low cost nitrogen-doped soybean meal carbon (SBMC) catalyst obtained from the simple carbonization of biomass soybean meal (SBM) in the presence of zinc chloride. This material exhibits excellent catalytic performance during acetylene hydrochlorination, with an initial acetylene conversion greater than 99% and 98% selectivity for vinyl chloride at 200 °C over 110 h. Analyses by X-ray photoelectron spectroscopy and temperature programmed desorption as well as catalytic activity evaluations show that pyridinic species are the active sites for hydrogen chloride, while pyrrolic N species are the main active sites for acetylene. An analysis of charge calculations based on model catalysts further indicates that the activity of pyrrolic N species essentially determines the performance of the SBMC catalyst. This investigation of the mechanism of acetylene hydrochlorination over SBMC confirms that such nitrogen-doped catalysts have two different active sites for the adsorption and activation of hydrogen chloride and acetylene molecules. This mechanism is different from that associated with metal chloride catalysts such as HgCl2. This SBMC catalyst is a potential alternative to HgCl2@AC catalysts for vinyl chloride synthesis and suggests a new means of designing carbon catalysts with basic surfaces for acetylene hydrochlorination.

Background: A subset of Hashimoto's thyroiditis (HT), reported as immunoglobulin G4 (IgG4) thyroiditis, is characterized by IgG4+ plasma cell-rich inflammation and marked sclerotic changes, which suggests a close relationship with immunoglobulin G4-related disease (IgG4-RD). However, to date, there is no consensus regarding the cutoff values used to define a significant IgG4+ plasma cell count in thyroid inflammation. We, therefore, sought to validate both the cutoff value of the comprehensive diagnostic criteria (CVC) and the cutoff value of thyroid-specific diagnostic criteria (CVT) for diagnosing IgG4 thyroiditis. Methods: One hundred twenty cases of HT were retrospectively reviewed. According to the CVC (IgG4+ plasma cells >10/HPF (high-power field) and IgG4+/IgG+ plasma cell ratio >40%) and the CVT (IgG4+ plasma cells >20/HPF and IgG4+/IgG+ plasma cell ratio >30%), cases were subclassified as IgG4 thyroiditis or non-IgG4 thyroiditis. Clinical, serological, sonographic, and histopathological characteristics of the two subsets, and the cases diagnosed as IgG4 thyroiditis using different thresholds were compared. Results: Both the CVC and CVT identified the same set of distinct clinical, laboratory, and sonographic features of the cases diagnosed as IgG4 thyroiditis. All 120 cases of HT were able to be divided into four distinct groups. Group A included the 25 cases who were assigned as IgG4 thyroiditis by both the CVC and CVT, whereas Group D included the 85 cases who did not meet either of the cutoff values. Group B and Group C comprised the borderline cases who only met one of the two thresholds. Based on histological evaluation, the cases in Group B who met the CVT demonstrated similar histological features of IgG4 thyroiditis. Conclusions: Although both of the cutoff values can efficiently distinguish IgG4 thyroiditis from its non-IgG4 counterpart, the thyroid-specific cutoff value (CVT, IgG4+ plasma cells >20/HPF, and IgG4+/IgG+ plasma cell ratio >30%) can better identify borderline cases of HT with more fibrotic changes, which may represent an early phase lesion of IgG4 thyroiditis. We propose a new series of clinical and pathological diagnostic clues for both endocrinologists and pathologists to improve the early recognition of IgG4 thyroiditis.

Sulfotransferase family 1E member 1 (SULT1E1) is known to catalyze sulfoconjugation and play a crucial role in the deactivation of estrogen homeostasis, which is involved in tumorigenesis and the progression of breast and endometrial cancers. Our previous study has shown that the protein levels of SULT1E1 were decreased in breast cancer; however, the underlying mechanism is still poorly understood. In this study, we explored the functional and molecular mechanisms by which SULT1E1 influenced breast cancer. Here, we identified that overexpression of SULT1E1 inhibited breast cancer cell growth through inducing apoptosis and arresting cell cycle progression. Furthermore, enforced expression of SULT1E1 suppressed tumor cell migration and invasion. Moreover, we found that the activation of PPARγ was required for SULT1E1-mediated downregulation of C-myc, Cyclin D1, MMP-2 and MMP-9 as well as for cell apoptosis, migration and invasion. In addition, the overexpression of SULT1E1 significantly inhibited tumor growth in vivo. Taken together, our findings indicated that SULT1E1 performed its tumor suppressor characteristics by activating PPARγ, which provided a novel target for patients with breast cancer.

// Dong Wang 1 , Licheng Du 2 , Zhou Wang 1 , Xiangyan Liu 1 , Yejun Qin 3 , Qiangxiu Wang 3 , Zhe Yang 4 , Zhigang Yao 3 , Mo Shi 1 , Bin Shang 1 , Yang Jia 1 , Huaxia Chen 1 , Liang Qiao 1 , Xueqing Wang 1 , Zhaohua Xiao 1 and Zhenchuan Liu 1 1 Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China 2 Department of General Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China 3 Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China 4 Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China Correspondence to: Zhou Wang, email: wz620226@hotmail.com Keywords: esophageal neoplasms, survival analysis, receptor, fibroblast growth factor, type 1 Received: July 21, 2017 Accepted: August 27, 2017 Published: October 04, 2017 ABSTRACT Purpose : To investigate whether FGFR1 gene amplification is associated with clinicopathologic characteristics and its potential impact on survival in patients with resected esophageal squamous cell carcinoma (ESCC). Methods : Five hundred fifty-six ESCC patients undergoing curative resection of ESCC were retrospectively studied. FGFR1 gene copy number was determined in microarrayed tumor samples using fluorescent in situ hybridization (FISH) analysis. FGFR1 gene amplification status was prespecified as copy number ≥ 6 or FGFR1/CEN 8 ratio ≥ 2.2. FGFR1 expression was evaluated by immunohistochemistry. Overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method followed by the log rank test. Correlation with survival was examined using multivariate Cox regression. Results : FGFR1 amplification was identified in 67 (12.1%) patients; these patients had significantly shorter OS (50.0 vs 32.0 months; log rank; P

The present study aimed to investigate the impact of overexpression of long noncoding RNA PEG10 (lncRNA PEG10) on the proliferation, invasion and metastasis of hypopharyngeal squamous cell carcinoma (HSCC). Quantitative reverse transcription polymerase chain reaction was used to quantify lncRNA PEG10 expression levels in HSCC tumor tissues samples, para-carcinoma tissue samples and the HSCC FaDu cell line. Cell proliferation assays, Transwell invasion assays and wound healing assays were used to evaluate the effects of lncRNA PEG10 on FaDu cells in vitro. In 56 eligible patients, lncRNA PEG10 was expressed at higher levels in HSCC tumor tissues compared with para-carcinoma tissues, and significant associations were observed between increased tumor expression of lncRNA PEG10 and primary tumor size, lymph node status and tumor node metastasis stage. In the in vitro experimental studies, enhanced expression of lncRNA PEG10 was significantly associated with increased proliferation, invasion and metastasis of FaDu cells. lncRNA PEG10 was upregulated in HSCC, and its overexpression in HSCC cells promoted an increase in the tumorigenic activities of proliferation, invasion and migration. The potential underlying mechanisms require investigation in future studies.

Hepatocellular carcinoma related protein 1 (HCRP1), which is essential for internalization and degradation of ubiquitinated membrane receptors, is downregulated in several tumors and strongly affects the outcomes of cancer patients. It is reported the expression of HCRP1 is inversely related to epidermal growth factor receptor (EGFR) in breast cancer and lead to resistance to cetuximab in ovarian cancer. However, its exact mechanism in the progression of Hepatocellular carcinoma (HCC) remains unknown. Herein, HCRP1 expression and its clinical significance were examined in 101 HCC patients using immunohistochemistry. Cell proliferation, migration and invasion assays were conducted in HCC cell lines. EGFR activation and degradation were then observed after EGF inducing in HCRP1 knockdown HepG2 cells. In addition, we also detected whether epithelial-to-mesenchymal transition (EMT) was involved in the malignancy promoted by HCRP1. The results showed that 59 of the 101 HCC cases exhibited downregulation of HCRP1 expression (P

Gliomas are the most common primary malignant brain tumors in adults. Accurate grading is crucial as therapeutic strategies are often disparate for different grades and may influence patient prognosis. This study aims to provide an automated glioma grading platform on the basis of machine learning models. In this paper, we investigate contributions of multi-parameters from multimodal data including imaging parameters or features from the Whole Slide images (WSI) and the proliferation marker Ki-67 for automated brain tumor grading. For each WSI, we extract both visual parameters such as morphology parameters and sub-visual parameters including first-order and second-order features. On the basis of machine learning models, our platform classifies gliomas into grades II, III, and IV. Furthermore, we quantitatively interpret and reveal the important parameters contributing to grading with the Local Interpretable Model-Agnostic Explanations (LIME) algorithm. The quantitative analysis and explanation may assist clinicians to better understand the disease and accordingly to choose optimal treatments for improving clinical outcomes. The performance of our grading model was evaluated with cross-validation, which randomly divided the patients into non-overlapping training and testing sets and repeatedly validated the model on the different testing sets. The primary results indicated that this modular platform approach achieved the highest grading accuracy of 0.90 ± 0.04 with support vector machine (SVM) algorithm, with grading accuracies of 0.91 ± 0.08, 0.90 ± 0.08, and 0.90 ± 0.07 for grade II, III, and IV gliomas, respectively.

MicroRNAs (miRNAs) are 21–23-nucleotide, short, non-coding RNAs that play important roles in virtually all biological pathways in mammals and other multicellular organisms. The association of miR-221 and miR-222 (miR-221/222) for breast cancer is critical, but their detailed roles in its development and progression remain unclear. In the present study, we found that miR-221/222 were consistently up-regulated in breast cancer tissues. We then investigated the molecular mechanisms by which miR-221/222 contributed to breast cancer and identified growth arrest–specific transcript 5 (GAS5) as a direct target gene of miR-221/222. In contrast with the up-regulated expression levels of miR-221/222, GAS5 levels were significantly down-regulated and negatively correlated with miR-221/222 in breast cancer tissues. In addition, we showed that miR-221/222 inhibitors increased cellular apoptosis, miR-221/222 mimics decreased the cell apoptosis in breast cancer cells, and restoration of GAS5 expression attenuated the anti-apoptotic effects of miR-221/222 in breast cancer cells, indicating that GAS5 was a direct mediator of miR-221/222 function. Finally, we showed that miR-221/222 suppressed GAS5 expression significantly and enhanced tumor growth in a mouse model of breast cancer xenografts. The present study highlighted the important role of miR-221/222 as oncomiRs in breast cancer, which inhibited GAS5 translation. These findings may provide a new perspective for the molecular mechanism of breast carcinogenesis and provide a novel approach to the treatment of breast cancer.

Chemo-resistance is considered a key problem in triple negative breast cancer (TNBC) chemotherapy and as such, an urgent need exists to identify its exact mechanisms. Inhibitor of DNA binding factor 4 (ID4) was reported to play diverse roles in different breast cancer molecular phenotypes. In addition, ID4 was associated with mammary carcinoma drug resistance however its functions and contributions remain insufficiently defined. The expression of ID4 in MCF-7, MCF-7/Adr and MDA-MB-231 breast cancer cell lines and patients' tissues were detected by RT-PCR, western blot and immunohistochemistry. Furthermore, TCGA database was applied to confirm these results. Edu and CCK8 assay were performed to detect the proliferation and drug resistance in breast cancer cell lines. Transwell and scratch migration assay were used to detected metastasis. Western blot, TCGA database, Immunoprecipitation (IP), Chromatin Immunoprecipitation (ChIP) and Luciferase reporter assay were used to investigate the tumor promotion mechanisms of ID4. In this study, we report that the expression levels of ID4 appeared to correlate with breast cancers subtype differentiation biomarkers (including ER, PR) and chemo-resistance related proteins (including MRP1, ABCG2, P-gp). Down-regulation of ID4 in MCF-7/Adr and MDA-MB-231 breast cancer cell lines significantly suppressed cell proliferation and invasion, however enhanced Adriamycin sensitivity. We further demonstrated that the oncogenic and chemo-resistant effects of ID4 could be mediated by binding to CBF1 promoter region though combination with MyoD1, and then the downstream target MRP1 could be activated. We reveal for the first time that ID4 performs its function via a CBF1-MRP1 signaling axis, and this finding provides a novel perspective to find potential therapeutic targets for breast cancer chemotherapy.

The production of vinyl chloride (VCM) by pyrolysis of 1,2-dichloroethane (DCE) is an important process in the ethylene-based poly(vinyl chloride) industry. The pyrolysis is performed at temperatures above 500 °C, gives low conversions, and has high energy consumption. We have shown that N-doped carbon catalysts give excellent performances in DCE dehydrochlorination at 280 °C. The current understanding of the active sites, mechanism, and kinetics of DCE dehydrochlorination over N-doped carbon catalysts is limited. Here, we showed that pyridinic-N on a N-doped carbon catalyst is the active site for catalytic production of vinyl chloride monomer from DCE. The results of CO2 and DCE temperature-programmed desorption experiments showed that the pyridinic-N catalytic sites are basic, and the mechanism of dehydrochlorination on a N-doped carbon catalyst involves a carbanion. A kinetic study of dehydrochlorination showed that the surface reaction rate on the N-doped carbon catalyst was the limiting step in the catalytic dehydrochlorination of DCE. This result enabled clarification of the dehydrochlorination mechanism and optimization of the reaction process. These findings will stimulate further studies to increase our understanding of the relationship between the base strength and catalytic performance. The results of this study provide a method for catalyst optimization, namely modification of the amount of pyridinic-N and the base strength of the catalyst, to increase the surface reaction rate of DCE dehydrochlorination on N-doped carbon catalysts.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with high morbidity and mortality. The aim of this study was to assess the diagnostic role of HCC related protein 1 (HCRP1) and inhibitor of DNA Binding 4 (ID4) as novel reliable markers for HCC diagnosis. Methods: Immunohistochemistry for HCRP1, ID4 and Glypican-3 (GPC-3) was performed in 98 cases of HCCs, 15 large regenerative nodules arising in cirrhotic livers, 12 hepatocellular adenomas (HCA), 10 focal nodular hyperplasias (FNH), and 20 specimens of normal liver tissues (NL). Results: HCRP1 immunoactivity was decreased in 64 of 98 (65.3%) HCC cases but present in almost all of the benign liver nodules (56/57, 98.2%, P < 0.001). 68 of 98 (69.4%) and 70 of 98 (71.4%) HCC cases were positive for ID4 and GPC-3, respectively, which were much higher than in benign lesions. Even though HCRP1 is highly specific (98.25%) in differentiating well differentiated HCC (WDHCC) from benign liver nodules, it has only a limited value because of its low sensitivity (37.5%), neither for the ID4, GPC-3 alone or combination (P > 0.05). The expression of HCRP1 alone could efficiently distinguish WDHCC from moderate-poorly differentiated HCC (M-PHCC), and the combination of using either two or three markers could notably increase the diagnosis accuracy (P < 0.05). Conclusion: HCRP1 and ID4 represent potentially novel valuable biomarkers for distinguishing HCC from benign liver nodules, and it is recommended to use the combination of HCRP1, ID4 and GPC-3 as a panel in HCC differentiation estimation.

The microRNA-29 family (miRNA-29s) has three mature members, miR-29a, miR-29b and miR-29c, which have been implicated in the regulation of the pathogenesis of Alzheimer׳s disease (AD). The miR-29 family members exhibit differential regulation in various diseases and different subcellular distribution. In the present study, we initially investigated differential expression of miR-29c in the hippocampus and the frontal cortex of the young APPswe/PSΔE9 mouse brain, accompanied by inverse expression of neurone navigator 3 (NAV3), a regulator of axon guidance. We observed that miR-29c directly mediated downregulation of NAV3 protein expression in vitro. The mouse NAV3 mRNA has a functional miR-29c binding site in the 3′ UTR, which localized in the position between 830–836 bp of 3′UTR region, slightly different from human NAV3 mRNA binding site. These observations suggest that miR-29c may be involved in neurodegenerative processes by regulating NAV3 expression in the young AD mouse.

Objective To detect the expression of TGF-β1 in Wilms' tumor and association with disease progression. Methods Immunohistochemistry was used to examine TGF-β1 expression in 51 primary tumors and 17 invasions/metastases. Transient transfection was performed to establish Wilms' tumor cells with high TGF-β1 expression (TGF-β1-WT), and the expression level of TGF-β1 was detected by Western blot analysis. Invasive capacity of the transfected cells was evaluated by transwell analysis. Results The positive expression rate of TGF-β1 was 50.98% (26/51) and 82.35% (14/17) in primary WT tissues and associated invasive/metastatic tissues, respectively. The higher level of TGF-β1 expression in primary WT tumors was relative to invasion/metastasis (p = 0.048). The expression of TGF-β1 between primary WT and matched invasive/metastatic tissues was concordant (p = 0.219). TGF-β1-WT cells showed more invasive capacity than GFP-WT and WT cells. TGF-β1 expression status was associated with disease-free survival (DFS) (50.2 months vs. 75.4 months, p = 0.022) but not overall survival (OS) (62.3 months vs. 75.8 months, p = 0.141). Conclusions Positive expression of TGF-β1 in WT was correlated with tumor invasion and disease progression, which might be useful in identifying patients at high risk of unfavorable outcomes.

Objective To determine the expression of the gene programmed cell death 5 ( PDCD5) and its protein PDCD5 in laryngeal squamous cell carcinoma and to analyse possible correlations with clinicopathological parameters. Methods PDCD5 mRNA expression was assessed using reverse transcription–polymerase chain reaction and expression of PDCD5 protein was studied using Western blot analysis and immunohistochemistry in laryngeal squamous cell carcinoma and morphologically normal para-carcinoma tissue. Results A total of 41 laryngeal squamous cell carcinoma and 29 normal para-carcinoma tissue specimens were examined. Expression of both PDCD5 mRNA and PDCD5 protein was significantly reduced in laryngeal squamous cell carcinoma compared with normal tissue. Expression was correlated with clinical stage and histological grade, but was not associated with age, sex, location of primary tumour or the presence of lymph node metastases. Conclusion The expression of PDCD5 and its protein were shown to be reduced in laryngeal squamous cell carcinoma. The functional importance of PDCD5 as a regulating agent in cell apoptosis suggests that it may play a key role in tumour pathogenesis and development.

Objectives Investigations of FOXP3 protein expression in cervical oesophageal cancer cells and the number of FOXP3 + lymphocytes infiltrating tumour tissue were undertaken. Methods FOXP3 protein expression and FOXP3 + tumour-infiltrating lymphocytes were studied immunohistochemically, in cervical oesophageal cancer tissue samples from 42 cases and paracancerous tissue samples from 30 of these cases. Results The percentage of parenchymal cells expressing FOXP3 protein was significantly higher in cancer tissue (42.9%, 18/42) than in paracancerous tissue 6.67% (two of 30). FOXP3 + lymphocyte infiltration was significantly more frequent in cancer (38.1%, 16/42) than in paracancerous (13.33%, four of 30) tissue. FOXP3 protein expression in cancer parenchymal cells in patients with lymph node metastasis was significantly greater than expression in those without lymph node metastasis. FOXP3 protein expression was significantly higher in cancer tissue samples from clinical stage III or IV than those from stage I or II disease. FOXP3 + lymphocyte infiltration of tumours was significantly greater in patients with lymph node metastasis than in those without metastasis. Conclusions Abnormal FOXP3 expression in cervical oesophageal cancer parenchyma and FOXP3 + lymphocyte infiltration might be closely related to metastasis of this cancer by promoting immune escape of the tumour. FOXP3 might be a potential marker for the assessment of postoperative metastasis in cervical oesophageal cancer.

Estrogen has a protective role in vascular functions and estrogen levels are modulated by estrogen sulfotransferase (SULT1E1). In this study, we investigated the effects of the peroxisome proliferator-activated receptor-α (PPAR-α) agonist WY14643 and insulin-like growth factor-1 (IGF-1) on the expression and activity of SULT1E1 in vascular cells. Human umbilical vein endothelial cells (HUVECs) and human umbilical artery smooth muscle cells (HUASMCs) were primarily cultured from fresh umbilical cord. SULT1E1 was highly expressed in HUVECs and HUASMCs according to immunofluorescence microscopy detection. WY14643 decreased, while IGF-1 increased, SULT1E1 mRNA and SULT1E1 protein levels, as demonstrated by RT-qPCR and western blot analysis, respectively, in the HUVECs and HUASMCs. SULT1E1 activity was indicated by counting the transformed 3H-estradiol sulfate from 3H-labeled 17β-estradiol added into the cell culture medium. The activity of SULT1E1 reduced following treatment with WY14643, whereas SULT1E1 activity was enhanced in the presence of IGF-1. The human SULT1E1 promoter-reporter plasmid was constructed. The activity of the SULT1E1 promoter increased 30-fold compared with the pGL3-basic vector. The PPAR-α agonist WY14643 downregulated, while IGF-1 upregulated, the luciferase activity of the SULT1E1 promoter. In conclusion, the PPAR-α agonist WY14643 and IGF-1 may regulate SULT1E1 expression at the transcriptional level and modulate the levels of active estrogens in endothelial cells and smooth muscle cells, thereby affecting the physiology and pathophysiology of vascular walls.

Previous study showed that hepatocellular carcinoma related protein 1 (HCRP1) is decreased in breast cancer. HCRP1 expression is inversely related to epithelial growth factor receptor (EGFR) in breast cancer tissues, and patients with breast cancer expressing lower HCRP1 tended to suffer a shorter life expectancy. However, the detailed biological functions of HCRP1 in breast cancer as well as the interaction between HCRP1 and EGFR remain unexplored. In this study, we examined HCRP1 expression in breast cancer tissues and cell lines by western blot. Thereafter, we performed transwell migration and matrigel invasion assays after siRNA interference and lentiviral vector of HCRP1 infection. To further investigate the interaction between HCRP1 downregulation and EGFR signaling pathway, we evaluated the phosphorylation status of EGFR, Erk1/2 and Akt by western blot following HCRP1-siRNA transfection. Moreover, we investigated the in vivo functions of HCRP1 using a breast cancer xenograft model. We found that HCRP1 depletion significantly promoted breast cancer migration and invasion while HCRP1 overexpression produced an opposite effect. In addition, HCRP1 depletion decreased EGFR degradation and enhanced phosphorylation of EGFR. Interestingly, HCRP1 depletion also led to insensitivity to EGFR inhibitors treatment. The in vivo experiment confirmed the metastasis inhibition function of HCRP1. The present data indicate that HCRP1 inhibits breast cancer metastasis through downregulating EGFR phosphorylation.

Objective: To investigate the relationship between Eg5 expression and prognosis of patients with non-muscle invasive bladder urothelial carcinoma. Methods: Eg5 expression was examined by immunohistochemistry in non-muscle invasive urothelial carcinoma specimens (grade: G1, 32 cases; G2, 92 cases; and G3, 39 cases. Stage: pTa, 49 cases and pT1, 114 cases). The correlation between clinicopathological characteristics and Eg5 expression was evaluated. The prognostic significance of Eg5 immunoreactivity was analyzed through survival analysis in 163 non-muscle invasive cases that were treated with transurethral resection and adjuvant intravesical instillations. Results: The expression of Eg5 was significantly associated with tumor grade (P = 0.006), with a trend towards significant association with stage (P = 0.057). The 163 patients with non-muscle invasive tumors were regularly followed with the mean of 32.52 (from 6 to 72) months. Univariate analysis showed Eg5 overexpression exhibited a significant unfavorable influence on intravesical recurrence (P = 0.012) while having only a marginal correlation with disease progression (P = 0.070). Subsequent Cox hazard multivariate analysis showed that both grade (P = 0.045) and Eg5 expression (P = 0.029) were independent predictors for early intravesical recurrence. Conclusions: Overexpression of Eg5 correlates with poor differentiation of bladder cancer, and it represents an independent prognostic factor in predicting early intravesical recurrence in non-muscle invasive bladder carcinoma patients.

Our previous study found that thyroid-stimulating hormone promoted sterol regulatory element-binding protein-2 (SREBP-2) expression and suppressed AMP-activated protein kinase (AMPK) activity in the liver, but it was unclear whether there was a direct link between TSH, AMPK and SREBP-2. Here, we demonstrate that the 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR)-induced activation of AMPK directly inhibited the expression of SREBP-2 and its target genes HMGCR and HMGCS, which are key enzymes in cholesterol biosynthesis, and suppressed the TSH-stimulated up-regulation of SREBP-2 in HepG2 cells; similar results were obtained in TSH receptor knockout mice. Furthermore, AMPK, an evolutionally conserved serine/threonine kinase, phosphorylated threonine residues in the precursor and nuclear forms of SREBP-2, and TSH interacted with AMPK to influence SREBP-2 phosphorylation. These findings may represent a molecular mechanism by which AMPK ameliorates the hepatic steatosis and hypercholesterolemia associated with high TSH levels in patients with subclinical hypothyroidism (SCH).

An efficient synthesis of aromatic lactate esters is reported via highly regioselective Friedel-Crafts reactions of electron-rich aromatic compounds with pyruvate ester promoted by TiCl4 in the presence of basic Al2O3. The utility of the reaction is shown by the efficient synthesis of the pesticide cycloprothrin in high yield.

The device is controlled by TMS320F2812 microprocessor. It mainly includes signal acquisition circuit, keyboard circuit, Chinese / English LCD display circuit, the calendar clock circuits, alarm circuits, relay output circuit, communications interface circuits, DI / DO circuit, power circuit and CPU circuit and so on. In addition, the device integrates a sensor transmission circuit, so it can directly connect with temperature pressure sensors to achieve high-precision measurement and monitoring. According to needs of users, it can work in different modes without the additional controller respectively. The equipment can communicate with each other by CAN bus or RS485. It mainly can realize the control and analysis of equipment status, failure predication and diagnosis, information management, etc.

To investigate the relationship between Eg5 expression and prognosis of patients with non-muscle invasive bladder urothelial carcinoma.Eg5 expression was examined by immunohistochemistry in non-muscle invasive urothelial carcinoma specimens (grade: G1, 32 cases; G2, 92 cases; and G3, 39 cases. Stage: pTa, 49 cases and pT1, 114 cases). The correlation between clinicopathological characteristics and Eg5 expression was evaluated. The prognostic significance of Eg5 immunoreactivity was analyzed through survival analysis in 163 non-muscle invasive cases that were treated with transurethral resection and adjuvant intravesical instillations.The expression of Eg5 was significantly associated with tumor grade (P = 0.006), with a trend towards significant association with stage (P = 0.057). The 163 patients with non-muscle invasive tumors were regularly followed with the mean of 32.52 (from 6 to 72) months. Univariate analysis showed Eg5 overexpression exhibited a significant unfavorable influence on intravesical recurrence (P = 0.012) while having only a marginal correlation with disease progression (P = 0.070). Subsequent Cox hazard multivariate analysis showed that both grade (P = 0.045) and Eg5 expression (P = 0.029) were independent predictors for early intravesical recurrence.Overexpression of Eg5 correlates with poor differentiation of bladder cancer, and it represents an independent prognostic factor in predicting early intravesical recurrence in non-muscle invasive bladder carcinoma patients.

Large dish solar concentrator is consist of many small parabolic mirrors. In the processing and installation, small mirror will deviate from the ideal state, meanwhile some errors including non-parallelism of solar rays, tracking error etc will affect the performance of the concentrator. Based on the rotation parabolic’s condenser characteristics and some previous literature’s ideas. we take one part of the large dish to analysis the size of focal spot which is affected by non-parallelism of solar rays, ray tracing error, and the shift of the receiving surface position these three factors. Then, through a series of numerical simulations, we can get the analysis results which present a reference for the dish solar concentrator design and installation.

Raman spectroscopy on single, living epithelial cells captured in a laser trap is shown to have diagnostic power over colorectal cancer. This new single-cell technology comprises three major components: primary culture processing of human tissue samples to produce single-cell suspensions, Raman detection on singly trapped cells, and diagnoses of the cells by artificial neural network classifications. It is compared with DNA flow cytometry for similarities and differences. Its advantages over tissue Raman spectroscopy are also discussed. In the actual construction of a diagnostic model for colorectal cancer, real patient data were taken to generate a training set of 320 Raman spectra and a test set of 80. By incorporating outlier corrections to a conventional binary neural classifier, our network accomplished significantly better predictions than logistic regressions, with sensitivity improved from 77.5% to 86.3% and specificity improved from 81.3% to 86.3% for the training set and moderate improvements for the test set. Most important, the network approach enables a sensitivity map analysis to quantitate the relevance of each Raman band to the normal-to-cancer transform at the cell level. Our technique has direct clinic applications for diagnosing cancers and basic science potential in the study of cell dynamics of carcinogenesis.

This PDF file contains the errata for “JBO Vol. 12 Issue 03 Paper 2756853” for JBO Vol. 12 Issue 03

A single-cell diagnostic technique for epithelial cancers is developed by utilizing laser trapping and Raman spectroscopy to differentiate cancerous and normal epithelial cells. Single-cell suspensions were prepared from surgically removed human colorectal tissues following standard primary culture protocols and examined in a near-infrared laser-trapping Raman spectroscopy system, where living epithelial cells were investigated one by one. A diagnostic model was built on the spectral data obtained from 8 patients and validated by the data from 2 new patients. Our technique has potential applications from epithelial cancer diagnosis to the study of cell dynamics of carcinogenesis.

Background Coactivator-associated arginine methyltransferase 1 (CARM1) belongs to the protein arginine methyltransferase family. CARM1 has been reported to be associated with high grade tumors in breast cancer. It still remains unknown the expression pattern of CARM1 in breast cancer and its relationships with clinicopathological characteristics and molecular subtypes. Methods Two hundred forty-seven invasive breast cancer cases were collected and prepared for tissue array. There were thirty-seven tumors with benign glandular epithelium adjacent to the tumors among these cases. Molecular subtype and CARM1 expression were investigated using immunohistochemistry. Results Cell staining was observed in the cytoplasm and/or nucleus. Staining for CARM1 was significantly stronger in adenocarcinoma compared with adjacent benign epithelium. There is a significant correlation between CARM1 overexpression with young age, high grade, estrogen receptor (ER) and progesterone receptor (PR) negative, increased p53 expression, and high Ki-67 index. Our study demonstrated CARM1 overexpression was associated with an increase in the protein expression of HER2. Furthermore, our data indicated CARM1-overexpression rate were remarkably higher in HER2 subtype (69.6%), luminal B subtype (59.6%) and TN subtype (57.1%) compared with luminal A subtype (41.3%). Conclusions CARM1 expression was increased in invasive breast cancer. CARM1 overexpression was associated with poorly characterized clinicopathologic parameters and HER2 overexpression. There were significant differences between different molecular subtypes in their relationship to CARM1 overexpression. Our results support the value of using CARM1 in prognostic stratification of breast cancer patients and its potential therapeutic implications in targeting treatment. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4116338491022965

Background Beta-catenin, a component of the Wingless/Wnt signaling pathway, can activate target genes linking with the adenomatous polyposis coli (APC) gene in colorectal cancer. The purpose of this study is to investigate whether nuclear beta-catenin overexpression in metastatic sentinel lymph node(s) [SLN(s)] is associated with synchronous liver metastasis. Methods Clinicopathological data from 355 patients (93 cases with liver metastasis and 262 cases without liver metastasis) were reviewed. Beta-catenin expression in metastatic SLN(s) and liver metastatic lesions was examined by immunohistochemistry. The association of nuclear beta-catenin expression in metastatic SLN(s) and liver metastatic lesions was evaluated, and the relationship between nuclear beta-catenin expression and clinicopathological characteristics was analyzed. Finally, univariate and logistic multivariate regression analyses were adopted to discriminate the risk factors of liver metastasis. Results Nuclear beta-catenin overexpression in metastatic SLN(s) was observed in 70 patients with liver metastasis and 31 patients without liver metastasis (75.3% vs. 11.8%; P < 0.001). Nuclear beta-catenin expression was noted in all the metastatic lesions. Spearman rank correlation analysis demonstrated that nuclear beta-catenin expression in metastatic SLN(s) had a positive correlation with that in metastatic lesions (r = 0.425, P < 0.001). Univariate and multivariate analyses indicated that nuclear beta-catenin overexpression in metastatic SLN(s) correlated with liver metastasis. Conclusions Nuclear beta-catenin overexpression in metastatic SLN(s) is strongly associated with liver metastasis and may contribute to predict liver metastasis.