Expression of Toll-Like Receptor 4 in Glomerular Endothelial Cells under Diabetic Conditions.
AuthorsTakata S, Sawa Y, Uchiyama T, Ishikawa H
JournalActa Histochem Cytochem
PubMed ID23554538
'Diabetic conditions promote glomerulosclerosis by mesangial cells but the mechanisms are not fully elucidated. The present study evaluated the expression of toll-like receptor 4 in glomerular endothelial cells in the streptozotocin (STZ)-induced type 1 diabetic mouse (ICR-STZ) and the type 2 diabetic KK/TaJcl mouse which were fed a high fat ... More
Detection of low abundance RNA molecules in individual cells by flow cytometry.
AuthorsHanley MB, Lomas W, Mittar D, Maino V, Park E
JournalPLoS One
PubMed ID23441230
'A variety of RNA analysis technologies are available for the detection of RNA transcripts from bulk cell populations. However, the techniques for RNA detection from individual cells have been limited. Here we adapt a novel in situ signal amplification method (the RNAScope® detection platform) for the analysis of intracellular RNAs ... More
Monitoring tumorigenesis and senescence in vivo with a p16(INK4a)-luciferase model.
AuthorsBurd CE, Sorrentino JA, Clark KS, Darr DB, Krishnamurthy J, Deal AM, Bardeesy N, Castrillon DH, Beach DH, Sharpless NE
JournalCell
PubMed ID23332765
'Monitoring cancer and aging in vivo remains experimentally challenging. Here, we describe a luciferase knockin mouse (p16(LUC)), which faithfully reports expression of p16(INK4a), a tumor suppressor and aging biomarker. Lifelong assessment of luminescence in p16(+/LUC) mice revealed an exponential increase with aging, which was highly variable in a cohort of ... More
Specific regulation of NRG1 isoform expression by neuronal activity.
AuthorsLiu X, Bates R, Yin DM, Shen C, Wang F, Su N, Kirov SA, Luo Y, Wang JZ, Xiong WC, Mei L
JournalJ Neurosci
PubMed ID21653853
'Neuregulin 1 (NRG1) is a trophic factor that has been implicated in neural development, neurotransmission, and synaptic plasticity. NRG1 has multiple isoforms that are generated by usage of different promoters and alternative splicing of a single gene. However, little is known about NRG1 isoform composition profile, whether it changes during ... More
Adenosquamous carcinoma of the head and neck: relationship to human papillomavirus and review of the literature.
AuthorsMasand RP, El-Mofty SK, Ma XJ, Luo Y, Flanagan JJ, Lewis JS
JournalHead Neck Pathol
PubMed ID21305368
'Adenosquamous carcinoma (ADSC) of the head and neck is an aggressive variant of squamous cell carcinoma (SCC). Certain variants of head and neck SCC are human papillomavirus (HPV)-related and have better prognosis. The relationship of HPV to head and neck ADSC has not been investigated. We searched our files for ... More
High-risk human papillomavirus E6/E7 mRNA detection by a novel in situ hybridization assay strongly correlates with p16 expression and patient outcomes in oropharyngeal squamous cell carcinoma.
AuthorsUkpo OC, Flanagan JJ, Ma XJ, Luo Y, Thorstad WL, Lewis JS
JournalAm J Surg Pathol
PubMed ID21836494
'Human papillomavirus (HPV) is established as causative in oropharyngeal squamous cell carcinomas (OSCCs), being detected in 50% to 80% of tumors by DNA in situ hybridization (ISH) and/or polymerase chain reaction. However, these tests do not assess viral transcription. Many consider E6/E7 messenger ribonucleic acid (mRNA) the best indicator of ... More
GENCODE: the reference human genome annotation for The ENCODE Project.
AuthorsHarrow J, Frankish A, Gonzalez JM, Tapanari E, Diekhans M, Kokocinski F, Aken BL, Barrell D, Zadissa A, Searle S, Barnes I, Bignell A, Boychenko V, Hunt T, Kay M, Mukherjee G, Rajan J, Despacio-Reyes G, Saunders G, Steward C, Harte R, Lin M, Howald C, Tanzer A, Derrien T, Chrast J, Walters N, Balasubramanian S, Pei B, Tress M, Rodriguez JM, Ezkurdia I, van Baren J, Brent M, Haussler D, Kellis M, Valencia A, Reymond A, Gerstein M, Guigó R, Hubbard TJ
JournalGenome Res
PubMed ID22955987
'The GENCODE Consortium aims to identify all gene features in the human genome using a combination of computational analysis, manual annotation, and experimental validation. Since the first public release of this annotation data set, few new protein-coding loci have been added, yet the number of alternative splicing transcripts annotated has ... More
Partial p16 staining in oropharyngeal squamous cell carcinoma: extent and pattern correlate with human papillomavirus RNA status.
AuthorsLewis JS, Chernock RD, Ma XJ, Flanagan JJ, Luo Y, Gao G, Wang X, El-Mofty SK
JournalMod Pathol
PubMed ID22596101
'Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma has unique biology and better outcomes. p16 immunostaining is used as a surrogate marker for transcriptionally active HPV. Although diffuse staining is generally accepted as positive, the significance of partial staining has not been established, nor has the cutoff for extent of p16 ... More
Spindle cell carcinomas of the head and neck rarely harbor transcriptionally-active human papillomavirus.
AuthorsWatson RF, Chernock RD, Wang X, Liu W, Ma XJ, Luo Y, Wang H, El-Mofty SK, Lewis JS
JournalHead Neck Pathol
PubMed ID23536041
'Spindle cell carcinoma is an uncommon variant of squamous cell carcinoma characterized by spindled or pleomorphic cells which appear to be a true sarcoma but are actually epithelial. Some head and neck squamous cell carcinoma variants can be human papillomavirus (HPV)-related and have improved outcomes. We sought to determine if ... More
The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations.
AuthorsYan KS, Chia LA, Li X, Ootani A, Su J, Lee JY, Su N, Luo Y, Heilshorn SC, Amieva MR, Sangiorgi E, Capecchi MR, Kuo CJ
JournalProc Natl Acad Sci U S A
PubMed ID22190486
'The small intestine epithelium undergoes rapid and continuous regeneration supported by crypt intestinal stem cells (ISCs). Bmi1 and Lgr5 have been independently identified to mark long-lived multipotent ISCs by lineage tracing in mice; however, the functional distinctions between these two populations remain undefined. Here, we demonstrate that Bmi1 and Lgr5 ... More
RNAscope: a novel in situ RNA analysis platform for formalin-fixed, paraffin-embedded tissues.
AuthorsWang F, Flanagan J, Su N, Wang LC, Bui S, Nielson A, Wu X, Vo HT, Ma XJ, Luo Y
JournalJ Mol Diagn
PubMed ID22166544
'In situ analysis of biomarkers is highly desirable in molecular pathology because it allows the examination of biomarker status within the histopathological context of clinical specimens. Immunohistochemistry and DNA in situ hybridization (ISH) are widely used in clinical settings to assess protein and DNA biomarkers, respectively, but clinical use of ... More
In situ validation of an intestinal stem cell signature in colorectal cancer.
AuthorsZiskin JL, Dunlap D, Yaylaoglu M, Fodor IK, Forrest WF, Patel R, Ge N, Hutchins GG, Pine JK, Quirke P, Koeppen H, Jubb AM
JournalGut
PubMed ID22637696
'Wnt/Tcf, Lgr5, Ascl2 and/or Bmi1 signalling is believed to define the mouse intestinal stem cell niche(s) from which adenomas arise. The aim of this study was to determine the relevance of these putative intestinal stem cell markers to human colorectal cancer.' ... More
Long noncoding RNAs and human disease.
AuthorsWapinski O, Chang HY
JournalTrends Cell Biol
PubMed ID21550244
'A new class of transcripts, long noncoding RNAs (lncRNAs), has been recently found to be pervasively transcribed in the genome. Multiple lines of evidence increasingly link mutations and dysregulations of lncRNAs to diverse human diseases. Alterations in the primary structure, secondary structure, and expression levels of lncRNAs as well as ... More
Validation of a novel diagnostic standard in HPV-positive oropharyngeal squamous cell carcinoma.
AuthorsSchache AG, Liloglou T, Risk JM, Jones TM, Ma XJ, Wang H, Bui S, Luo Y, Sloan P, Shaw RJ, Robinson M
JournalBr J Cancer
PubMed ID23412100
'Human papillomavirus (HPV) testing in oropharyngeal squamous cell carcinoma (OPSCC) is now advocated. Demonstration of transcriptionally active high-risk HPV (HR-HPV) in fresh tumour tissue is considered to be the analytical ''gold standard''. Clinical testing has focused on formalin-fixed paraffin-embedded (FFPE) tissue at the expense of sensitivity and specificity. Recently, a ... More
Transcriptionally-active high-risk human papillomavirus is rare in oral cavity and laryngeal/hypopharyngeal squamous cell carcinomas--a tissue microarray study utilizing E6/E7 mRNA in situ hybridization.
AuthorsLewis JS, Ukpo OC, Ma XJ, Flanagan JJ, Luo Y, Thorstad WL, Chernock RD
JournalHistopathology
PubMed ID22360821
Human papillomavirus is well established in oropharyngeal squamous cell carcinoma as both causative and prognostic, but its significance in non-oropharyngeal tumours is unclear. In particular, the significance of finding viral DNA is not known. We sought to evaluate nonoropharyngeal squamous cell carcinomas for transcriptionally-active human papillomavirus and to compare this ... More
Viable circulating tumour cell detection using multiplex RNA in situ hybridisation predicts progression-free survival in metastatic breast cancer patients.
AuthorsPayne RE, Wang F, Su N, Krell J, Zebrowski A, Yagüe E, Ma XJ, Luo Y, Coombes RC
JournalBr J Cancer
PubMed ID22538972
Current approaches for detecting circulating tumour cells (CTCs) in blood are dependent on CTC enrichment and are based either on surface epithelial markers on CTCs or on cell size differences. The objectives of this study were to develop and characterise an ultrasensitive multiplex fluorescent RNA in situ hybridisation (ISH)-based CTC ... More
Quantitative in situ measurement of estrogen receptor mRNA predicts response to tamoxifen.
AuthorsBordeaux JM, Cheng H, Welsh AW, Haffty BG, Lannin DR, Wu X, Su N, Ma XJ, Luo Y, Rimm DL
JournalPLoS One
PubMed ID22606272
Quantification of mRNA has historically been done by reverse transcription polymerase chain reaction (RT-PCR). Recently, a robust method of detection of mRNA utilizing in situ hybridization has been described that is linear and shows high specificity with low background. Here we describe the use of the AQUA method of quantitative ... More
Relevance of TNBS-colitis in rats: a methodological study with endoscopic, histologic and Transcriptomic [corrected] characterization and correlation to IBD.
AuthorsBrenna Ø, Furnes MW, Drozdov I, van Beelen Granlund A, Flatberg A, Sandvik AK, Zwiggelaar RT, Mårvik R, Nordrum IS, Kidd M, Gustafsson BI
JournalPLoS One
PubMed ID23382912
Rectal instillation of trinitrobenzene sulphonic acid (TNBS) in ethanol is an established model for inflammatory bowel disease (IBD). We aimed to 1) set up a TNBS-colitis protocol resulting in an endoscopic and histologic picture resembling IBD, 2) study the correlation between endoscopic, histologic and gene expression alterations at different time ... More
T-cell infiltration correlates with CXCL10 expression in ganglia of cynomolgus macaques with reactivated simian varicella virus.
AuthorsOuwendijk WJ, Abendroth A, Traina-Dorge V, Getu S, Steain M, Wellish M, Andeweg AC, Osterhaus AD, Gilden D, Verjans GM, Mahalingam R
JournalJ Virol
PubMed ID23269790
Ganglia of monkeys with reactivated simian varicella virus (SVV) contained more CD8 than CD4 T cells around neurons. The abundance of CD8 T cells was greater less than 2 months after reactivation than that at later times and correlated with that of CXCL10 RNA but not with those of SVV ... More
Hamster-adapted Sin Nombre virus causes disseminated infection and efficiently replicates in pulmonary endothelial cells without signs of disease.
AuthorsSafronetz D, Prescott J, Haddock E, Scott DP, Feldmann H, Ebihara H
JournalJ Virol
PubMed ID23388711
To date, a laboratory animal model for the study of Sin Nombre virus (SNV) infection or associated disease has not been described. Unlike infection with Andes virus, which causes lethal hantavirus pulmonary syndrome (HPS)-like disease in hamsters, SNV infection is short-lived, with no viremia and little dissemination. Here we investigated ... More
A mouse model of chronic prostatic inflammation using a human prostate cancer-derived isolate of Propionibacterium acnes.
AuthorsShinohara DB, Vaghasia AM, Yu SH, Mak TN, Brüggemann H, Nelson WG, De Marzo AM, Yegnasubramanian S, Sfanos KS
JournalProstate
PubMed ID23389852
Prostatic inflammation has been linked to a number of prostatic diseases such as benign prostatic hyperplasia (BPH), prostatitis syndromes, and prostate cancer. Major unanswered questions include what pathogenic mechanisms, such as bacterial infections, may drive the accumulation of inflammatory infiltrates in the human prostate, and how inflammation might contribute to ... More
High heregulin expression is associated with activated HER3 and may define an actionable biomarker in patients with squamous cell carcinomas of the head and neck.
AuthorsShames DS, Carbon J, Walter K, Jubb AM, Kozlowski C, Januario T, AnDo Fu L, Xiao Y, Raja R, Jiang B, Malekafzali A, Stern H, Settleman J, Wilson TR, Hampton GM, Yauch RL, Pirzkall A, Amler LC
JournalPLoS One
PubMed ID23468880
Tumors with oncogenic dependencies on the HER family of receptor tyrosine kinases (RTKs) often respond well to targeted inhibition. Our previous work suggested that many cell lines derived from squamous cell carcinomas of the head and neck (SCCHNs) depend on autocrine signaling driven by HER2/3 dimerization and high-level co-expression of ... More
Automated quantitative RNA in situ hybridization for resolution of equivocal and heterogeneous ERBB2 (HER2) status in invasive breast carcinoma.
AuthorsWang Z, Portier BP, Gruver AM, Bui S, Wang H, Su N, Vo HT, Ma XJ, Luo Y, Budd GT, Tubbs RR
JournalJ Mol Diagn
PubMed ID23305906
Patient management based on HER2 status in breast carcinoma is an archetypical example of personalized medicine but remains hampered by equivocal testing and intratumoral heterogeneity. We developed a fully automated, quantitative, bright-field in situ hybridization technique (RNAscope), applied it to quantify single-cell HER2 mRNA levels in 132 invasive breast carcinomas, ... More
In situ hybridization in human and rodent tissue by the use of a new and simplified method.
AuthorsSørdal Ø, Qvigstad G, Nordrum IS, Gustafsson B, Waldum HL
JournalAppl Immunohistochem Mol Morphol
PubMed ID22688353
In situ hybridization (ISH) is a method that detects and localizes DNA or RNA in morphologically preserved tissue and cell preparations. The method is based on the principle that DNA or RNA will undergo hydrogen binding to complimentary sequences. Selective probes are labeled and used in order to detect specific ... More
Detection of HPV infection in head and neck squamous cell carcinoma: a practical proposal.
AuthorsDreyer JH, Hauck F, Oliveira-Silva M, Barros MH, Niedobitek G
JournalVirchows Arch
PubMed ID23503925
Detecting human papillomavirus (HPV) infection in head and neck squamous cell carcinoma (HNSCC) is clinically relevant, but there is no agreement about the most appropriate methodology. We have studied 64 oropharyngeal carcinomas using p16 immunohistochemistry, HPV DNA in situ hybridisation (ISH) and HPV DNA polymerase chain reaction (PCR) followed by ... More
In situ analysis of HER2 mRNA in gastric carcinoma: comparison with fluorescence in situ hybridization, dual-color silver in situ hybridization, and immunohistochemistry.
AuthorsKim MA, Jung JE, Lee HE, Yang HK, Kim WH
JournalHum Pathol
PubMed ID23084583
The importance of anti-HER2 therapy has focused attention on the ability of clinical assays to correctly assign HER2 amplification status. In the present study, we evaluated HER2 mRNA expression using a new mRNA in situ detection technique called RNAscope in 211 cases of formalin-fixed, paraffin-embedded gastric carcinoma. In addition, we ... More
Identification of a disease-defining gene fusion in epithelioid hemangioendothelioma.
AuthorsTanas MR, Sboner A, Oliveira AM, Erickson-Johnson MR, Hespelt J, Hanwright PJ, Flanagan J, Luo Y, Fenwick K, Natrajan R, Mitsopoulos C, Zvelebil M, Hoch BL, Weiss SW, Debiec-Rychter M, Sciot R, West RB, Lazar AJ, Ashworth A, Reis-Filho JS, Lord CJ, Gerstein MB, Rubin MA, Rubin BP
JournalSci Transl Med
PubMed ID21885404
Integrating transcriptomic sequencing with conventional cytogenetics, we identified WWTR1 (WW domain-containing transcription regulator 1) (3q25) and CAMTA1 (calmodulin-binding transcription activator 1) (1p36) as the two genes involved in the t(1;3)(p36;q25) chromosomal translocation that is characteristic of epithelioid hemangioendothelioma (EHE), a vascular sarcoma. This WWTR1/CAMTA1 gene fusion is under the transcriptional ... More
A novel RT-PCR method for quantification of human papillomavirus transcripts in archived tissues and its application in oropharyngeal cancer prognosis.
AuthorsGao G, Chernock RD, Gay HA, Thorstad WL, Zhang TR, Wang H, Ma XJ, Luo Y, Lewis JS, Wang X
JournalInt J Cancer
PubMed ID22821242
Oropharyngeal squamous cell carcinoma (SCC) is strongly associated with human papillomavirus (HPV) infection, which is distinctively different from most other head and neck cancers. However, a robust quantitative reverse transcription PCR (RT-qPCR) method for comprehensive expression profiling of HPV genes in routinely fixed tissues has not been reported. To address ... More
REG gene expression in inflamed and healthy colon mucosa explored by in situ hybridisation.
Authorsvan Beelen Granlund A, Østvik AE, Brenna Ø, Torp SH, Gustafsson BI, Sandvik AK
JournalCell Tissue Res
PubMed ID23519454
The regenerating islet-derived (REG) gene family encodes a group of proteins highly expressed in several human pathologies, many of which are associated with epithelial inflammation. All human family members, namely REG1A, REG1B, REG3A and REG4, are closely related in genomic sequence and all are part of the c-type lectin superfamily. ... More
Detection of transcriptionally active high-risk HPV in patients with head and neck squamous cell carcinoma as visualized by a novel E6/E7 mRNA in situ hybridization method.
AuthorsBishop JA, Ma XJ, Wang H, Luo Y, Illei PB, Begum S, Taube JM, Koch WM, Westra WH
JournalAm J Surg Pathol
PubMed ID23060353
Evidence for transcriptional activation of the viral oncoproteins E6 and E7 is regarded as the gold standard for the presence of clinically relevant human papillomavirus (HPV), but detection of E6/E7 mRNA requires RNA extraction and polymerase chain reaction amplification-a challenging technique that is restricted to the research laboratory. The development ... More
Cyclin D1-a prognostic marker in oropharyngeal squamous cell carcinoma that is tightly associated with high-risk human papillomavirus status.
AuthorsScantlebury JB, Luo J, Thorstad WL, El-Mofty SK, Lewis JS
JournalHum Pathol
PubMed ID23566410
Human papillomavirus-related oropharyngeal squamous cell carcinoma has a unique biology and improved prognosis. A new focus is to identify prognostic biomarkers specifically in this human papillomavirus-positive cohort. We analyzed cyclin D1 immunostaining on a tissue microarray of patients with known clinical follow-up and p16 and human papillomavirus status (by E6/E7 ... More
Restriction of intestinal stem cell expansion and the regenerative response by YAP.
AuthorsBarry ER, Morikawa T, Butler BL, Shrestha K, de la Rosa R, Yan KS, Fuchs CS, Magness ST, Smits R, Ogino S, Kuo CJ, Camargo FD
JournalNature
PubMed ID23178811
A remarkable feature of regenerative processes is their ability to halt proliferation once an organ's structure has been restored. The Wnt signalling pathway is the major driving force for homeostatic self-renewal and regeneration in the mammalian intestine. However, the mechanisms that counterbalance Wnt-driven proliferation are poorly understood. Here we demonstrate ... More
Myeloid cell receptor LRP1/CD91 regulates monocyte recruitment and angiogenesis in tumors.
AuthorsStaudt ND, Jo M, Hu J, Bristow JM, Pizzo DP, Gaultier A, VandenBerg SR, Gonias SL
JournalCancer Res
PubMed ID23633492
Recruitment of monocytes into sites of inflammation is essential in the immune response. In cancer, recruited monocytes promote invasion, metastasis, and possibly angiogenesis. LDL receptor-related protein (LRP1) is an endocytic and cell-signaling receptor that regulates cell migration. In this study, we isografted PanO2 pancreatic carcinoma cells into mice in which ... More