tbuckley/cabot-search huggingface dataset:
THU0454 Changes in DNA Methylation Related to Smoking Are Associated with Ra. an Epigenome Wide Association Study in Monozygotic RA Discordant Twin Pairs
Authors: A.J. Svendsen, K. Gervin, R. Lyle, C. Nielsen, G. Houen, P. Junker, K. Kyvik, Q. Tan
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> There is increasing evidence for a pathogenetic role of DNA methylation changes in RA. Monozygotic (MZ) twins provide a unique opportunity to study the epigenetic effects in complex diseases like RA. Recent estimates on DNA methylation in twins showed a mean genome-wide heritability of 18%. Recent studies indicate that DNA methylation may be an intermediary factor of genetic risk in RA.<sup>1</sup> In addition, tobacco smoking, which has emerged as the single most important environmental risk factor for RA, leads to extensive Genome-Wide changes in DNA methylation.<sup>2</sup> <h3>Objectives</h3> To identify differentially methylated positions (DMPs) associated with RA and smoking. <h3>Methods</h3> Blood-derived DNA from 28 monozygotic RA discordant twin pairs was analyzed for epigenome wide methylation (EWAS) using Illumina HumanMethylation450 array. The twins were characterized with regard to smoking, DMARD-treatment, anti-CCP, and the pair specific genetic variables shared epitope and PTPN22 as well as age and sex. We used a mixed model designed for EWAS on discordant twins taking these covariates as well as batch effects into consideration. <h3>Results</h3> A total of 407 CpG sites were differentially methylated in RA patients related to smoking with p&lt;0.01, adjusted for false discovery rates. Biological pathway analysis revealed that a large number of functional gene clusters were affected, e.g. macrophage activation, sphingomyelin metabolic process, apoptotic cell clearance, and histone demethylase activity. <h3>Conclusions</h3> These observations indicate that tobacco smoking elicits profound epigenetic modifications in RA when adjusting other RA associated covariates. <h3>References</h3> Liu Y, Aryee MJ, Padyukov L, Fallin MD, Hesselberg E, Runarsson A, et al. Epigenome-wide association data implicate DNA methylation as an intermediary of genetic risk in rheumatoid arthritis. Nat Biotech 2013; 31(2): 142-7. Zeilinger S, Kuhnel B, Klopp N, Baurecht H, Kleinschmidt A, Gieger C, et al. Tobacco smoking leads to extensive genome-wide changes in DNA methylation. PLoS One 2013; 8(5): e63812. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2461
Ga-67 Visualization of the Coexistence of Two Mucosa-Associated Lymphoid Tissue (MALT) Lymphomas in the Thyroid and Stomach
Authors: MITUSTAKA FUKUMOTO, ATUSHI KUROHARA, NAOKI AKAGI, DAISUKE YOSHIDA, SHOJI YOSHIDA
Journal: Clinical Nuclear Medicine (1998)

Ga-67 scans of a 26-year-old woman visualized intense uptake in the thyroid and stomach, which led to the diagnosis of two mucosa-associated lymphoid tissue (MALT) lymphomas coexisting in one individual. The involvement of two different organs by lymphoma is uncommon, and that by MALT lymphoma is particularly rare. A relation between gastric and thyroid lymphoma has been recognized because both organs develop from the foregut embryologically.
Abstract 1676: Associations between hormone therapy with incident colorectal cancer by p53 protein expression in a population-based cohort of older women
Authors: Lori S. Tillmans, Robert Vierkant, Alice Wang, Charles Lynch, Kristin Anderson, Amy French, Robert Haile, Lisa Harnack, John Potter, Susan Slager, Thomas Smyrk, Stephen Thibodeau, James Cerhan, Paul Limburg
Journal: Cancer Research (2012)

Abstract Background: Cigarette smoking (CS) is an established colorectal cancer (CRC) risk factor. The p53 protein, encoded by the TP53 tumor suppressor gene that is commonly mutated in CRC, is important in cell cycle arrest needed to repair DNA damage or induce apoptosis to prevent tumor propagation. In this prospective cohort study, we examined CS-associated CRC risks by p53 protein expression level in the population-based Iowa Women's Health Study (IWHS). Methods: The IWHS recruited 41,836 randomly selected Iowa women, ages 55-69 years, with a valid driver's license at study entry (1986). CS and other exposure variables were assessed at baseline, by self-report. Incident CRC cases were ascertained by annual linkage with the Iowa Cancer Registry. Archived, paraffin-embedded tissue specimens were collected from 732 CRC cases diagnosed through 12/31/2002. CS was categorized by smoking status (never, current, former), average number of cigarettes per day (1-19, 20-39, &amp;gt; 40) and cumulative pack-years (1-19, 20-39, &amp;gt; 40). P53 protein expression was determined by immunohistochemistry on tissue microarrays. Tumor cores were scored by combining both staining intensity and percent of cells stained to determine negative, low or high p53 protein expression levels. Multivariate Cox regression models were fit to estimate relative risks (RRs) and 95% confidence intervals (CIs). Results: Of the 732 available CRC cases, 486 (66%) had complete CS and p53 data. Associations between CS and CRC subtypes defined by p53 expression level are shown in the Table. Conclusions: These data demonstrate no clear heterogeneity of CS with CRC subtypes defined by p53 expression levels among older women. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1676. doi:1538-7445.AM2012-1676
Detecting Vulvar Cancer with Inguinal Lymph Node Metastases by Dual-Phase Tl-201 Scan
Authors: CHIA-HUNG KAO
Journal: Clinical Nuclear Medicine (2003)

From the Department of Nuclear Medicine, China Medical College Hospital, Taichung, Taiwan Received for publication January 23, 2002. Revision accepted May 13, 2002. Reprint requests: Chia-Hung Kao, Department of Nuclear Medicine, China Medical College Hospital, No. 2, Yuh-Der Road, Taichung 404, Taiwan. E-mail: [email protected]
Endoscopic resection of small-bowel submucosal nodule
Authors: Siddharth Javia, Shashideep Singhal
Journal: Endoscopy (2016)

A 67-year-old woman presented for evaluation after positive findings from fecal immunochemical testing. Colonoscopy showed a 2-cm submucosal nodule in the terminal ileum. Superficial biopsies from the lesion were unrevealing. Over-the-scope clip (OTSC)-assisted resection was planned. An OTSC (size 12/6, type gc) was applied to the base of the lesion and hot snare resection was performed above the clip ([Fig. 1], [Video 1]). The collected tissue was submitted for pathological examination, which showed lipoma. No procedure-related complications were seen.
Abstract 2704: Ectopic expression of CHST11 promotes proliferation and migration of human breast cancer cells.
Authors: Alice Behrens, Fariba Jousheghany, Aiwei Yao-Borengasser, Thomas Kieber-Emmons, Behjatolah Monzavi-Karbassi
Journal: Cancer Research (2013)

Abstract Introduction. We have previously demonstrated that the expression levels of carbohydrate (chondroitin 4) sulfotransferase-11 (CHST11) correlates with P-selectin binding and aggressiveness (basal-like, triple-negative and mesenchymal phenotype) of human breast cancer. The present study was performed to establish stably transfected cell lines and study the functional role of CHST11 in human breast cancer cells. Methods. MCF7 cells were transfected with a plasmid vector containing the CHST11 coding sequence. Stable transfectants, MCF-7-CHST11, were established. Flow cytometry and real-time PCR were used for expression analysis. Metastatic phenotype of cells was characterized through conduction of proliferation and migration assays. Morphology and growth pattern of MCF-7-CHST11 cells were monitored and compared to parental MCF-7 cells. Results. We observed that MCF-7-CHST11 reacted strongly with anti-chondroitin sulfate A (CS-A) antibody and recombinant P-selectin. CS-A is the immediate product of CHST11 activity. CHST11 expression significantly affected cell proliferation as MCF-7-CHST11 cells grew much faster. Migration assay using transwell chamber showed high migratory potential for MCF-7-CHST11 cells as compared to the parental MCF-7 cells. The significant migratory advantage was not proliferation dependent. The CHST11expression affected the morphology of cells and cell spreading behavior consistent with more efficient anchorage independent growth. Colony formation in soft agar, Invasion and adhesion assays are being performed at the present time. We are planning more experiments to study mechanisms involved. Conclusions. The data confirm that the CHST11 products on the cell surface can serve as P-selectin ligands. The results indicate that the CHST11 expression can affect metastatic phenotype of cancer cells by promoting cellular proliferation and migratory potential. Citation Format: Alice Behrens, Fariba Jousheghany, Aiwei Yao-Borengasser, Thomas Kieber-Emmons, Behjatolah Monzavi-Karbassi. Ectopic expression of CHST11 promotes proliferation and migration of human breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2704. doi:10.1158/1538-7445.AM2013-2704
Abstract 420: Physiological β-catenin signaling regulates pluripotency genes in cancer microcell hybrids
Authors: Yue Cheng, Arthur Kwok Leung Cheung, Josephine Mun Yee Ko, Yee Peng Phoon, Maria L. Lung
Journal: Cancer Research (2012)

Abstract Both β-catenin signaling and Nanog were previously reported to be involved in cell fusion-mediated somatic cell reprogramming. It remains unclear as to how the β-catenin signaling pathway is initiated and whether this pathway may directly control the expression of core stem cell factors such as Nanog and Oct4. Since β-catenin signaling is a predominating force for the regulation of cellular fate and basic levels of this signaling are needed for somatic cell reprogramming, we speculate that transfer of a single copy of chromosome 3, where β-catenin maps and is controlled by its natural regulators, into somatic cancer cells may appropriately induce this pathway and switch on the expression of endogenous pluripotency genes in recipient cells. We previously generated human nasopharyngeal (HONE1) and esophageal (SLMT1) carcinoma hybrid cells with an intact copy of transferred chromosome 3. At both transcriptional and translational levels, we detected obvious expression of genes related to the Wnt/β-catenin pathway in HONE1/chromosome 3 hybrid cells. In these hybrid cells, β-catenin, c-Myc, Axin2, Tcf1, Sox2, Klf4, Oct4, and Nanog were either strongly expressed or up-regulated. The loss of region that contains B-catenin locus in transferred chromosome 3 abolishes the expression of core stem cell genes. The control of these gene activities by physiological β-catenin signaling was further confirmed in HONE1/chromosome 17 hybrids that contain the downstream components of β-catenin signaling Axin2 and Stat3, but was not detected in hybrids with an irrelevant transferred chromosome and SLMT1 cells that had a relatively high level of endogenous β-catenin expression. We also found that HONE1 hybrid cells have stem cell-like properties, including spheroid formation, up-regulation of CD24+ and CD44+ populations and expression of various embryonic markers. Additionally, chromosome 3 transfer induced epithelial-mesenchymal transformation (EMT) events in HONE1 cells that caused different expression of adhesion molecules and up-regulation of their regulators and other markers such as Twist, Snail, Slug, ZEB1, Sip1, and E-cadherin. As expected, we detected that p53, Rb1, and Smad2 involved pathways were activated in HONE1 hybrid cells, suggesting that physiological β-catenin signaling, via multiple signaling pathways, regulates both pluripotency networks and EMT events. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 420. doi:1538-7445.AM2012-420
Treatment of Male Infertility
Authors: Stuart S. Howards
Journal: New England Journal of Medicine (1995)

Fifteen percent of couples are subfertile — that is, they have less-than-normal fertility. In approximately 30 percent of the cases, an important abnormality is identified in only the man, and in another 20 percent abnormalities are detected in both partners. Thus, there is a male factor in infertility in half of the couples. The evaluation should begin with a complete history taking, physical examination, and appropriate laboratory tests. Unfortunately, even after a thorough evaluation, the cause of a man's lack of normal fertility usually remains unknown. Since it is very difficult to develop a rational treatment plan to correct a . . .
Minefields in their Hearts, by Ed Roberta J Apfel, Bennet Simon
Authors: M. Carballo
Journal: BMJ (1997)

Ed Roberta J Apfel, Bennet Simon Yale University Press, £22.50, pp 256 ISBN 0 300 06570 1

Violence is not new to human society, but at the end of the 20th century it has come to assume a more dominant part of our lives than at any other time in recent history. Wars, ethnic persecution, urban social disorganisation, seemingly institutionalised poverty, and the organised sexual abuse of children are starting to focus our concern on the health and social consequences of child directed, and sometimes child perpetrated, aggression.

Violence against children is not necessarily a part of, or a result of, poverty. Nor has it always been used as an …
Serotyping and Genetic Analysis in the Selection of Related Renal-Allograft Donors
Authors: V. A. Wonham, H. J. Winn, P. S. Russell
Journal: New England Journal of Medicine (1971)

Thirty-two recipients of 33 renal allografts from related donors were divided into three groups by serotyping and genetic analysis. In the first group, eight patients inherited the same HL-A complexes as their donors. Seven have had excellent courses, with complete rehabilitation; one has recurrent glomerulonephritis. In the second group, seven patients inherited one HL-A complex in common with their donors and had very good serologic matches for the other. All had evidence of rejection, but six have had excellent courses; two have stable but subnormal function. In the third group 16 patients shared one HL-A complex with their donors but had poor serologic matches for the other; one differed by both complexes from his donor. Three patients have had excellent courses though two show decreasing creatinine clearances. Ten had unsatisfactory courses resulting in death, nephrectomy or poor rehabilitation; four have had intermediate courses. Intrafamilial donors can be selected so that the prognosis is excellent for rapid and complete rehabilitation.
Abstract 1573: MAGED4B drives oral carcinogenesis and is a promising peptide vaccine target for the treatment of oral squamous cell carcinoma
Authors: Kue Peng Lim, Chai Phei Gan, Chan Eng Chong, Rosnah Binti Zain, Mannil Thomas Abraham, Zainal Ariff Abdul Rahman, Soo-Hwang Teo, J Silvio Gutkind, Vyomesh Patel, Sathibalan Ponniah, Sok Ching Cheong
Journal: Cancer Research (2012)

Abstract MAGED4B is a member of the Melanoma Antigen Gene (MAGE) family. We demonstrated that MAGED4B is over-expressed in more than 50% of oral squamous cell carcinoma (OSCC) tissues and that the expression of MAGED4B is associated with lymph node metastasis and poor disease specific survival. OSCC cell lines over-expressing MAGED4B exhibited an increase in cell growth both in vitro and in vivo, and were significantly more resistant to UV-induced apoptosis compared to control cells, suggesting a role for MAGED4B in modulating cell death. Further, MAGED4B also promoted cell migration. MAGE proteins are good targets for cancer immunotherapy as they are highly immunogenic. We identified and synthesized MAGED4B peptides that were HLA-A2- specific and tested the ability of these peptides to generate an anti-tumour response using PBMCs from OSCC patients and healthy individuals. Firstly, the PBMC samples obtained from patients and healthy individuals were tested for HLA-A2 expression. Positive samples were analyzed for peptide-specific stimulation of IFN-γ and granzyme secretion ex-vivo via ELISPOT assay. Dendritic cells pulsed with these peptides were used to stimulate PBMC cultures, and were studied for IFN-γ and granzyme secretion. In parallel, the binding of the peptides to the MHC-Class I molecule was determined by the binding assay. Further, the ability of these bound peptides to interact with T cells was measured by the dimer assay. We demonstrated that all the peptides have good binding capacity with the MHC-Class I molecules. Moreover, the binding of these peptides on MHC-Class I molecules could attract and further interact with T cells. Notably, the PBMC stimulated once with peptide-pulsed dendritic cells or twice with peptide and peptide-pulsed dendritic cells showed peptide-specific cytotoxic activity against MAGED4B-expressing OSCC cell lines. In summary, we first demonstrated that MAGED4B drives oral carcinogenesis and second, showed that MAGED4B-specific peptides are apable of inducing anti-tumour specific immune responses. Taken together, this indicates that MAGED4B could be a promising peptide vaccine target for the treatment of OSCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1573. doi:1538-7445.AM2012-1573
Reversible Bone-Marrow Vacuolizations in Phenylketonuria
Authors: Joseph D. Sherman, Jordan B. Greenfield, David Ingall
Journal: New England Journal of Medicine (1964)

PHENYLKETONURIA is an inherited disorder of amino acid metabolism characterized biochemically by a deficiency of hepatic phenylalanine hydroxylase, inability to convert phenylalanine to tyrosine and accumulation of phenylalanine and its metabolic products in various body fluids.1 2 3 4 5 6 7 8 9 10 11 Clinically, the disorder is associated with mental retardation, a variety of neurologic findings, alterations in skin pigmentation and eczema.12 13 14 15 16 The mental retardation and other clinical manifestations have been prevented by the early use of restricted phenylalanine diets.17 18 19 20 21 22 23 24 The application of the Guthrie screening test25 in the neonatal period has greatly facilitated the early diagnosis of this disorder.Phenylketonuric children become anemic,26 27 28 and it is . . .
Abstract 799: Global genomic analysis identified PRKCI as a potential therapeutic target gene for human clear cell ovarian cancer.
Authors: Tsun Yee Tsang, Gayatry Mohapatra, Hiroaki Itamochi, Samuel C. Mok, Michael J. Birrer
Journal: Cancer Research (2013)

Abstract Clear cell ovarian cancer (CCOC), a rare epithelial ovarian cancer histotype, is more resistant to standard chemotherapy and has a worse prognosis than serous and endometrioid histotypes. We attempted to identify genes that are responsible for the aggressive behavior of CCOC and could be potential therapeutic targets using genomic and expression profilings. To identify gene amplification, genome-wide DNA copy number alterations were measured in 13 CCOC cell lines using high-resolution oligonucleotide array CGH (Agilent 105k Human Genome CGH Microarray). GISTIC analysis identified 16 amplified regions containing 391 genes. After comparison to our database of differentially expressed genes between human CCOC specimens and normal ovarian surface epithelium specimen (Affymetrix U133 Plus 2.0 microarrays), 45 of the amplified genes showed mRNA overexpression in CCOC specimens. Among the 45 genes, protein kinase C iota (PRKCI) was amplified in 9/13 CCOC cell lines and was overexpressed (6.7 fold) in CCOC specimens. Analysis using PathwayStudio software identified PRKCI mediated pathways for cell migration and invasion. Knock-down of PRKCI by transfection with PRKCI specific siRNAs suppressed cell migration and invasion in KOC-7c and OVISE cells. On the other hand, ectopic expression of PRKCI by transfection with PRKCI expressing vector enhanced cell migration and invasion in ES2 and TOV21G cells. The results from the present study therefore suggested that PRKCI may promote metastasis and serve as a potential target gene for treatment of human clear cell ovarian cancer. Citation Format: Tsun Yee Tsang, Gayatry Mohapatra, Hiroaki Itamochi, Samuel C. Mok, Michael J. Birrer. Global genomic analysis identified PRKCI as a potential therapeutic target gene for human clear cell ovarian cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 799. doi:10.1158/1538-7445.AM2013-799
Abstract 2405: Treatment of human dendritic cells with Saccharomyces cerevisiae (yeast) reduces number and function of regulatory T cells (Tregs) and enhances the ratio of antigen-specific effectors to Tregs
Authors: Vittore Cereda, Matteo Vergati, Ngar-Yee Huen, Maria Giovanna di Bari, James L. Gulley, Alex Franzusoff, Jeffrey Schlom, Kwong Y. Tsang
Journal: Cancer Research (2010)

Abstract It has been demonstrated that recombinant Saccharomyces cerevisiae yeast vector containing the transgene encoding carcinoembryonic antigen (yeast-CEA) activates human dendritic cells (DCs) and stimulates CEA-specific T-cell responses. Numerous studies have shown that regulatory T cell (Treg) function plays an important role in immune modulation. We compared the effects of yeast-treated DCs and CD40L-matured DCs on the number and functionality of CD4+CD25+CD127-FoxP3+ Tregs. Human DCs were treated with yeast or CD40L and cocultured with isolated autologous CD4+ T cells for 5 days, then the phenotype and function of the CD4+ T cells were analyzed. CD4+CD25+CD127- T cells isolated from the coculture of CD4+ T cells plus yeast-treated DCs had a lower expression of FoxP3 and decreased suppressive function compared to CD4+CD25+CD127- T cells isolated from the coculture of CD4+ T cells plus CD40L-treated DCs. Also, compared to the coculture of CD4+ T cells plus CD40L-treated DCs, the coculture of CD4+ T cells plus yeast-treated DCs showed increases in the ratio of CD4+CD25+ activated T cells to Tregs and in the production of Th1-related cytokines (IL-2, TNF-α, IFN-γ) and IL-6. In addition, yeast-treated DCs used as antigen-presenting cells (APCs) incubated with CEA enhanced the proliferation of CEA-specific CD4+ T cells in carcinoma patients compared to the use of CD40L-matured DCs used as APCs. This is the first study to report on the role of yeast-treated human DCs in reducing Treg frequency and functionality and thus enhancing antitumor immune response. These results provide a rationale for the use of yeast as a vector in cancer vaccines. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2405.