tbuckley/cabot-search huggingface dataset:
FRI0263 Prospective study of primary biliary cirrhosis associated with systemic sclerosis: Analysis of the clinical, biological and microvascular aspects at first follow-up visit
Authors: M. Koenig, J.-L. Senécal, C. Vincent, M.J. Fritzler, M. Poliquin, M. Dominguez, R. Leduc, F. Joyal
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Primary biliary cirrhosis (PBC) is frequently associated with connective tissue diseases, namely systemic sclerosis (SSc). Predictive factors for survival of patients with both PBC and SSc are controversial. In 2005, we started a prospective study of 100 PBC patients to determine the prevalence of SSc, to study the clinical, biological and microvascular aspects of patients that had both diseases, and to identify predictive factors for progression of hepatic disease. Results of first visit for 23 patients with PBC and SSc (PBC-SSc) and 23 patients with PBC only were presented during the 2008 EULAR congress. <h3>Objectives</h3> to report the clinical, biological and microvascular features of PBC patients at first follow-up visit. <h3>Methods</h3> The medical history, physical examination, biological investigations and quantitative nailfold capillary microscopy (NMC) were repeated at follow-up visit. <h3>Results</h3> 90 patients were available for a second visit after a mean follow-up of 3.05 years. Among them 19 had PBC only and SSc was present in 22 (23%) patients (19 limited cutaneous SSc and 3 early SSc). Signs of portal hypertension or hepatic failure were present in 4 (9.7%) patients. In PBC-SSc patients, a typical NCM SSc pattern was observed in 17 (77%) patients and was identical at follow-up visit. No patient with CBP only developed abnormal NCM at follow-up study. The Mayo score was similar in patients with vs without SSc and no signifcant difference was observed for level of Alkaline Phosphatase in patients with versus without SSc. <h3>Conclusions</h3> Presence of SSc did not worsen the evolution of PBC patients at first follow-up visit. In patients with SSc, the cutaneous and NCM patterns are stable. Long term follow-up is still ongoing to survey the occurrence of SSc associated complications, namely pulmonary hypertension and fibrosis. <h3>Disclosure of Interest</h3> None Declared
322 KIR AND HLA LOCI AS PREDICTORS OF HCC OUTCOME IN PATIENTS WITH HCV INFECTION
Authors: E. Cariani, M. Pilli, A. Zerbini, C. Rota, A. Olivani, P. Zanelli, A. Zanetti, T. Trenti, C. Ferrari, G. Missale
Journal: Journal of Hepatology (2013)
Abstract 2587: <i>In vitro</i> plasma stability of human anti-CD70 antibody drug conjugate, MDX-1203
Authors: Janette Sung, Kavitha Vemuri, David Passmore, Andrea Tatum, Tom Kempe, Peter Brams, Dan Derwin, Lourdes Thevanayagam, Mohan Srinivasan, Mary Huber, Chetana Rao, Allen Zhang, Charlie Cong, Bilal Sufi, Sanjeev Gangwar, Shrikant Deshpande, Vangipuram S. Rangan
Journal: Cancer Research (2010)

Abstract MDX-1203 is a human anti-CD70 antibody conjugated to a pro-drug containing DNA alkylating cytotoxic Drug A. Drug A is composed of the anti-tumor compound Drug B, containing an ester linked protecting group, and a maleimide containing cleavable peptide linker designed to facilitate conjugation to the antibody. Mechanism of action of ADCs involve antibody mediated tumor specific delivery, cellular uptake, and intracellular pro-drug release and activation. Understanding the stability of the peptide linker as well as the pro-drug in various plasma matrices is critical for the development of successful ADC therapeutic. We have generated mouse monoclonal antibodies that specifically recognize either the intact Drug A or Drug A without the protecting group. Using these antibodies, an ELISA method was developed to study in vitro plasma stability of pro-drug in MDX-1203. Our results indicate that the plasma stability of ester linked protecting group varies significantly depending on the animal species probably due to variation in the level of plasma esterase activity. In order to determine the peptide linker stability, a radiolabeled MDX-1203 with 14C radiolabel on Drug A was made. A Thin Layer Chromatography method was developed to determine the in vitro plasma stability of the peptide linker in different plasma matrices. Our results indicate that the peptide linker in MDX-1203 is stable at 37o C up to 6 days. Based on these experimental data, we propose a model for stability of the peptide linker as well as the pro-drug in MDX-1203 in various plasma matrices. 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 2587.
P18 Robo1/4-slit2 Expression In Pulmonary Vascular Cells: Implications For Pah?
Authors: J. Chowdhury, L. Ramakrishnan, T. Svermova, S. Mumby, D. Shao, S. Wort, A. Burke-Gaffney
Journal: Thorax (2014)

<h3>Introduction and objectives</h3> Pulmonary artery hypertension (PAH) is associated with inappropriate vascular remodelling and inflammation. Recent studies have shown that vascular cells express the transmembrane roundabout (Robo) proteins, Robo1 and Robo4, and that interaction with a secreted glycoprotein ligand, Slit2, controls cell migratory and inflammatory response. We hypothesise that Robo1, Robo4 and Slit2 are expressed on pulmonary artery (PA) endothelial cells (EC) and smooth muscle cells (SMC). We also hypothesise that Slit2 will modulate PAEC and PASMC migration and inflammatory mediator release. <h3>Methods</h3> Real-time-PCR determination of Robo1, Robo4 and Slit2 expression and the house-keeping gene, GAPDH, in PAEC, PASMC and for comparison, human umbilical vein endothelial cells (HUVEC); following incubation with TNFα (10ng/ml) or Slit2N (10nM) for 2h. Enzyme-linked immunosorbent assay measurements of granulocyte-macrophage-colony stimulating factor (GM-CSF) in supernatants of HUVEC, PAEC or PASMC pre-treated (1h) with Slit2N, followed by TNFα (17h). Migration assays (PAEC or PASMC) towards serum-containing medium (0.05 and 0.02%, respectively), for 4h with/ without Slit2N. <h3>Results</h3> Basal mRNA expression of Robo1, Robo4 and Slit2 was detected in PAEC, PASMC and HUVEC (n = 3–4). Slit2N (2h) significantly (p &lt; 0.05, n = 3) decreased Robo4 and Slit2 mRNA expression, but not Robo1, by 35% in PAEC; and had no effect on HUVEC or PASMC. TNFα had no significant effects on Robo1, Robo4 or Slit2, regardless of cell type. Despite a small (23%), but significant (p &lt; 0.05) reduction of GM-CSF release from TNFα-activated HUVEC (n = 7), no similar effects were seen in PAEC or PASMC (n = 3). Moreover, whilst PAEC or PASMC migration to serum-containing medium increased (2.7- and 5.3-fold, respectively), co-incubation with Slit2 had no significant effect. <h3>Conclusion</h3> The novel discovery of Robo1, Robo4 and Slit2 mRNA in PAEC and PASMC; and that Slit2 down-regulated Robo4 and Slit2 in PAEC, but not PASMC/HUVEC, might suggest negative feedback on the Robo4-Slit2 axis unique to PAEC. That neither PAEC nor PASMC responded to Slit2 in functional assays could reflect limitations in experimental assays. However, down-regulation of Robo4-Slit2 in PAEC might also explain lack of effect on GM-CSF release, when compared with HUVEC. Further studies to better delineate the role of the Robo-Slit2 pathway in PAH are required.
Abstract 4204: Gene expression changes of DNA repair genes in lymphocytes of breast cancer patients
Authors: Julyann Perez-Mayoral, Jaime L. Matta, Julie Dutil
Journal: Cancer Research (2012)

Abstract Breast cancer is the most commonly diagnosed cancer among women in Puerto Rico. Previous studies have shown that dysregulation of DNA repair genes expression is important for carcinogenesis. However, most of the studies have focused on measuring DNA repair gene expression levels in tumor samples. Our preliminary studies had shown that women with decreased DNA repair capacity (DRC) are at increased risk of breast cancer. We hypothesized that changes in DRC levels may be partly explained by changes in gene expression of DNA repair genes. Our objective was to assess the contribution of the expression levels of 43 DNA repair and damage response genes in lymphocytes of breast cancer cases and controls of Puerto Rican origin. We measured the gene expression profile of 43 DNA repair genes in lymphocytes of 6 breast cancer cases with low DRC and 10 controls with high DRC using a custom SuperArray (SABiosciences). Of the 43 genes analyzed through the SuperArray, XPC, CETN2 and CCNH showed the largest fold-changes. To validate the results, we used a TaqMan-based gene expression assay in lymphocytes of 30 breast cancer cases and 30 controls. Our results showed that breast cancer cases had a 3.4x less XPC expression (p=0.002) and 2.2x less CCNH expression (p=0.01) than controls. Validation of the CETN2 SuperArray results is underway. In conclusion, we found that the XPC gene and CCNH were expressed less in breast cancer cases than in controls. Understanding the gene expression changes that occur prior to tumor development is an important step towards enhancing cancer prevention and detection strategies. 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 4204. doi:1538-7445.AM2012-4204
Th17 but not Th22 cells display pathological behaviour in arthritis
Authors: Jan Piet van Hamburg, Odilia B.J. Corneth, Sandra M.J. Paulissen, Nadine Davelaar, Patrick S. Asmawidjaja, Erik Lubberts
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Th17 cells (IL-17+IL-22+) are critically involved in the induction and progression of arthritis. Recently, Th22 cells were discovered, which were characterised by IL-22 expression in the absence of IL-17. However, it remains unclear whether IL-22 and Th22 cells, directly contribute to synovial inflammation. Therfore, the authors examined the potency of Th22 cells to activate synovial fibroblasts. In addition, it was investigated whether IL-22 is critical in Th17-mediated experimental arthritis. <h3>Materials and methods</h3> Th17 (CD4+CD45RO+CD25-CCR6+CCR4+CCR10-) and Th22 (CD4+CD45RO+CD25-CCR6+CCR4+CCR10-) cells were analysed in peripheral blood of treatment-naïve RA patients in comparison to age and sex matched healthy controls by flow cytometry. Furthermore, synovial fluid of patients with established RA was analysed for the presence of Th17 and Th22 cells. To test the contribution of IL-22 or Th22 in synovial inflammation, co-culture experiments of RA synovial fibroblasts (RASF) with Th22 and Th17 cells were performed. The in vivo relevance of IL-22 in synovial inflammation was investigated in a T cell-mediated arthritis model using mice deficient for IL-22. <h3>Results</h3> Both Th17 and Th22 cell populations were present in synovial fluid of patients with rheumatoid arthritis (RA) and were increased in peripheral blood of these patients compared to healthy controls. Upon interaction with RA synovial fibroblasts (RASF), Th17 cells induce activation of RASF resulting in an inflammatory feedback loop including autocrine IL-17A production. In Th17-RASF co-cultures, neutralisation of IL-22 resulted in increased RASF activation whereas the opposite was found by FICZ-induced IL-22 production. Moreover, Th17 cells were markedly more potent than Th22 cells in RASF activation. In addition, no difference in T cell-mediated experimental arthritis severity was found between IL-22 deficient mice compared to wild type mice. <h3>Conclusion</h3> These findings show that IL-22 and Th22 cells are less potent in inducing synovial inflammation compared to Th17 cells. These data imply that targeting Th17 cells rather than Th22 cells should be the focus for the treatment of T cell mediated joint inflammation.
Lipiodol as a marker for hepatocellular carcinoma migrating into the bile duct
Authors: W. Ridtitid, S. Chittmittrapap, C. Kriengkirakul, P. Kongkam, A. Janchai, R. Rerknimitr
Journal: Endoscopy (2010)

Transarterial chemoembolization (TACE) is an effective palliative treatment for unresectable hepatocellular carcinoma (HCC). However, several complications of TACE have been reported, including transient fever and pain after the procedure, hepatic infarction, liver abscess, hepatic failure, biliary stricture, and biloma [1] [2] [3], although acute obstructive cholangitis due to migration of the necrotic tumor after TACE is very rare. We report two cases of acute cholangitis secondary to biliary migration of necrotic hepatocellular carcinoma, both of which were diagnosed pre-endoscopically by computed tomography (CT) scan of the abdomen. Lipiodol stain was used as a marker for necrotic tumor migration.
Novel use of combined Dual Knife and endoloop for resection of a large pedunculated colon polyp
Authors: C. Yang, H. Yen
Journal: Endoscopy (2011)

A 56-year-old man underwent a screening colonoscopy, in which a pedunculated polyp, 4 cm × 2.8 cm in size with a 2.5-cm wide flat stalk, was identified in the sigmoid colon ([Fig. 1]). For the safe and complete resection of the polyp, prophylactic endoclips (Hx-600 – 135; Olympus, Hachioji-shi, Tokyo, Japan) were applied to both sides of the stalk but appeared to be ineffective ([Fig. 2]). We then applied a detachable endoloop (MAJ-254; Olympus, Hachioji-shi, Tokyo, Japan) over the stalk ([Fig. 3]). Because it was difficult to capture the stalk by going around the large head of the polyp using a conventional diathermic snare, we used the Dual Knife (KD-650 Q/U; Olympus, Hachioji-shi, Tokyo, Japan) with an electrosurgical generator (Endocut 50W; Coagulation 30W; ICC 200; ERBE Co., Tübingen, Germany) to cut the stalk under direct vision ([Fig. 4]; [Video 1]). After resection, the polyp was gently dragged into the rectum for spontaneous passage. Histological examination confirmed the polyp to be a tubulovillous adenoma without malignant change.
SP0046 Why IT Could BE Relevant to Study the Microbiome in Rheumatic Diseases
Authors: H. Leavis
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Autoimmune diseases, mostly, are multifactorial diseases. Genome wide association and twin studies can, so far, only explain the etiology of autoimmune diseases partly (∼10-50%). A significant role for external (and epigenetic) factors therefore exists in this matter. The amount of microbes in close contact with our body outnumbers the total amount of cells in the human body by a factor 10, and 50% of these microbes are located in the colon. Therefore, the human immune system is continuously exposed to the gut microbiota. Apart from contributing to development of the immune system, it may also contribute to immune aberrances. Normally tolerance is maintained by the intestinal barrier function (compartmentalization), nevertheless during different circumstances this tolerance can be lost. This presentation will cover the (assumed) interactions of gut microbiota and immune cells in relation to autoimmune diseases. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6300
Disulfiram modulates stemness and metabolism of brain tumor initiating cells in atypical teratoid/rhabdoid tumors
Authors: Seung Ah Choi, Jung Won Choi, Kyu-Chang Wang, Ji Hoon Phi, Ji Yeoun Lee, Kyung Duk Park, Dayoung Eum, Sung-Hye Park, Il Han Kim, Seung-Ki Kim
Journal: Neuro-Oncology (2014)

Atypical teratoid/rhabdoid tumors (AT/RT) are among the most malignant pediatric brain tumors. Cells from brain tumors with high aldehyde dehydrogenase (ALDH) activity have a number of characteristics that are similar to brain tumor initiating cells (BTICs). This study aimed to evaluate the therapeutic potential of ALDH inhibition using disulfiram (DSF) against BTICs from AT/RT. Primary cultured BTICs from AT/RT were stained with Aldefluor and isolated by fluorescence activated cell sorting. The therapeutic effect of DSF against BTICs from AT/RT was confirmed in vitro and in vivo. AT/RT cells displayed a high expression of ALDH. DSF demonstrated a more potent cytotoxic effect on ALDH+ AT/RT cells compared with standard anticancer agents. Notably, treatment with DSF did not have a considerable effect on normal neural stem cells or fibroblasts. DSF significantly inhibited the ALDH enzyme activity of AT/RT cells. DSF decreased self-renewal ability, cell viability, and proliferation potential and induced apoptosis and cell cycle arrest in ALDH+ AT/RT cells. Importantly, DSF reduced the metabolism of ALDH+ AT/RT cells by increasing the nicotinamide adenine dinucleotide ratio of NAD+/NADH and regulating Silent mating type Information Regulator 2 homolog 1 (SIRT1), nuclear factor-kappaB, Lin28A/B, and miRNA let-7g. Animals in the DSF-treated group demonstrated a reduction of tumor volume (P < .05) and a significant survival benefit (P = .02). Our study demonstrated the therapeutic potential of DSF against BTICs from AT/RT and suggested the possibility of ALDH inhibition for clinical application.
Abstract 187: Epigenetic memory during breast cancer progression is sustained by Smad signaling pathway
Authors: Sam Thiagalingam, Arthur W. Lambert, Sait Ozturk, Hamid M. Abdolmaleky, Panagiotis Papageorgis
Journal: Cancer Research (2010)

Abstract The molecular basis for the “epigenetic memory” that ensures maintenance of unique patterns of regulatory DNA methylation of selected genes responsible for cancer progression has remained elusive. Using a breast cancer progression model system, we found that hyperactive TGFβ-TGFβR-Smad2 signaling axis is involved in the maintenance of DNA hypermethylation mediated silencing of critical target genes to facilitate breast cancer progression. Disruption of TGFβ signaling caused a corresponding decrease in DNMT1 binding activity accompanied with increased expression of the target genes and acquisition of tumorigenic properties. These observations are consistent with passive demethylation of the newly synthesized DNA due to absence of sustained TGFβ-Smad signaling downstream events. In summary, we provide conclusive evidence that the reversal of the DNA hypermethylation status of gene promoters occurs as a result of TGFβ/Smad signaling pathway perturbation. By extension, we predict that inhibition of TGFβ-TGFβR-Smad2 signaling axis is an effective therapeutic strategy for breast cancer. 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 187.
Abstract 607: Restoration of p53 pathway signaling and apoptotic induction by prodigiosin and its structurally-related compound (NSC247562) in p53-deficient human colon carcinoma cells
Authors: Bo Hong, Fang Chen, David T. Dicker, Wafik S. El-Deiry
Journal: Cancer Research (2011)

Abstract p53 deficiency occurs commonly in human tumors, and contributes to radio- and chemo-resistance as well as an aggressive phenotype. It is believed that specific restoration of p53 will be beneficial in the treatment of aggressive or resistant tumors. Using a p53 mutant cell line (SW480) stably integrated p53-responsive reporter, we sought to identify small molecules with p53 rescue activity by screening of the NCI drug library. We found prodigiosin and its structurally related compound (NSC247562) can activate p53-dependent transcriptional activity in SW480, DLD1 as well as HCT116 p53−/− colon tumor cells. The induction of p53-dependent transcriptional activity by prodigiosin and its related compound (NSC247562) is stronger than that induced by CP31398 or ellipticine, which were previously reported as p53 function-restoring drugs. Furthermore, prodigiosin and its related compound (NSC247562) are found to induce the expression of p53 target genes (p21, Puma, DR5 and DR4) in mutant-p53 containing or p53-null human colon cancer cells. The restoration of p53 transcriptional activity by prodigiosin and its related compound (NSC247562) is accompanied by apoptotic induction as indicated by an increase of sub-G1 population and PARP cleavage. More importantly, prodigiosin and its related compound (NSC247562) induced tumor cell death, but have little or no detectable cytotoxicity towards normal human fibroblasts. Thus prodigiosin and its related compound may serve as promising compounds for the development of anticancer drugs which rescue p53 activity and induce cell death. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 607. doi:10.1158/1538-7445.AM2011-607
Pharmacokinetics of Taxol and Doxorubicin Administered Alone and in Combination by Continuous 72-Hour Infusion
Authors: S. L. Berg, K. H. Cowan, F. M. Balis, J. S. Fisherman, A. M. Denicoff, M. Hillig, D. G. Poplack, J. A. O'Shaughnessy
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Pharmacokinetics of Taxol and Doxorubicin Administered Alone and in Combination by Continuous 72-Hour Infusion Get access Stacey L. Berg, Stacey L. Berg Pediatric Branch, National Cancer InstituteBethesda, Md Correspondence to : Stacey L. Berg, M.D.., Pediatric Branch, Bldg. 10, Rm. 13N240, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD 20892. Search for other works by this author on: Oxford Academic PubMed Google Scholar Kenneth H. Cowan, Kenneth H. Cowan Medicine Branch, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar Frank M. Balis, Frank M. Balis Pediatric Branch, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar Jason S. Fisherman, Jason S. Fisherman Medicine Branch, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar Andrea M. Denicoff, Andrea M. Denicoff Medicine Branch, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar Marianne Hillig, Marianne Hillig Medicine Branch, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar David G. Poplack, David G. Poplack Pediatric Branch, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar Joyce A. O'Shaughnessy Joyce A. O'Shaughnessy Medicine Branch, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 2, 19 January 1994, Pages 143–145, https://doi.org/10.1093/jnci/86.2.143 Published: 19 January 1994 Article history Received: 12 May 1993 Revision received: 23 September 1993 Accepted: 28 October 1993 Published: 19 January 1994