tbuckley/cabot-search huggingface dataset:
P16 Non-invasive evaluation of fibrosis in paediatric chronic liver disease
Authors: E. Fitzpatrick, M.-S. Basso, A. Quaglia, R. R. Mitry, A. Dhawan
Journal: Gut (2011)

<h3>Introduction</h3> Outcome of liver disease in children is mainly determined by severity and progression of liver fibrosis. Liver biopsy is the accepted standard for evaluating fibrosis but is limited by the need for sedation in children, sampling error and risks including bleeding. <h3>Aim</h3> The aim of this study was to compare tools for non-invasive assessment of liver fibrosis in a paediatric cohort. <h3>Method</h3> Children were recruited at the time of liver biopsy and underwent transient elastography (TE) and blood collection. Liver biopsies were scored by a hepato-histopathologist from F0 (no fibrosis) to F4 (cirrhosis). Serum samples underwent analysis for the Enhanced Liver Fibrosis (ELF) test; comprising hyaluronic acid, P3NP and TIMP1 (iQur, UK). CK18-M30 levels (caspase cleavage fragments) were measured using ELISA. Biomarkers were compared to biopsy score. <h3>Results</h3> During the study period 101 children (62 boys) were enrolled. Median age: 13.6 (range 6–18) years. Diagnosis was autoimmune liver disease (AILD) in 27; non-alcoholic fatty liver disease (NAFLD) in 37; 13 children were post-transplant; 8 children had Hepatitis B/C; 5 had Wilson disease and the remainder miscellanous. TE was a good discriminator of fibrosis ≥ F2 (p&lt;0.001), ≥ F3 (p&lt;0.001) and F4 (p=0.003) with areas under the ROC curve of 0.78, 0.8 and 0.96 respectively. Data derived cut-offs for ≥ F1 were 6.1 kPa, ≥ F2; 6.8 kPa, ≥ F3; 8.3 kPa and F4; 14.1 kPa. Blood biomarkers were not as accurate in distinguishing severity of disease. ELF performed better with increasing stages of fibrosis. Area under the curve for cirrhosis was 0.77. CK18-M30 levels could distinguish significant fibrosis (≥ F2) (p=0.009) with an area under the ROC curve of 0.77, severe fibrosis (≥ F3) with an AUROC of 0.69 and cirrhosis (F4) with an AUROC of 0.69. Within the different diagnostic groups, again TE performed better than serum biomarkers with AUROC of 0.75 for ≥ F2 and 0.81 for ≥ F3 in NAFLD; 0.85 for ≥ F2, 0.94 for ≥ F3 and 1.0 for F4 in AILD; and in children post-transplant; 0.9 for ≥ F2 and 0.83 for ≥ F3. <h3>Conclusion</h3> To our knowledge, this is the largest paediatric study reported to date comparing TE and serum biomarkers for the non-invasive evaluation of fibrosis. TEwas a reliable tool in distinguishing different stages of liver fibrosis in paediatric patients. Blood biomarkers may be of use in combination with TE especially in the stratification of more severe disease. Routine use of these techniques may serve as a useful adjunct to liver biopsy for diagnostic purposes and provide a reliable method of non-invasively monitoring liver disease progression in children.
Abstract MS1-1: Noncoding RNA — The New Frontier in Breast Cancer Patients Management
Authors: GA Calin
Journal: Cancer Research (2010)

Abstract MicroRNA and other short or long non-codingRNAs alterations are involved in the initiation, progression and metastases of human breast cancer. The main molecular alterations are represented by variations in gene expression, usually mild and with consequences for a vast number of target protein coding genes. The causes of the widespread differential expression of non-codingRNAs in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the processing machinery. MicroRNA and other short or long non-codingRNAs expression profiling of human tumors has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment. In addition, profiling has been exploited to identify non-codingRNAs that may represent downstream targets of activated oncogenic pathways or that are targeting protein coding genes involved in breast cancer. Recent studies proved that miRNAs and non-coding ultraconserved genes are main candidates for the elusive class of cancer predisposing genes and that other types of non-codingRNAs participate in the genetic puzzle giving rise to the breast malignant phenotype. These discoveries could be exploited for the development of useful markers for diagnosis and prognosis, as well as for the development of new RNA-based cancer therapies. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr MS1-1.
Abstract 2714: Expression and functional analysis of LGR4 in normal and cancer cells of human colon.
Authors: Jing Yi, Wei Xiong, Xing Gong, Qingyun Liu
Journal: Cancer Research (2013)

Abstract LGR4 (leucine-rich repeat containing G protein-coupled receptor 4) and its two closely related homologues LGR5 and LGR6 have been shown to function as receptors of R-spondins to potentiate Wnt signaling. The RSPO/LGR4-6 ligand receptor system has essential functions in embryonic development, cell proliferation and survival of adult stem cells. Particularly, LGR4 is required for the survival of intestinal stem cells and the maintenance of gut epithelium while LGR5 is specifically expressed in crypt stem cells. Wnt signaling is frequently dysregulated in various types of cancer, especially in colorectal cancers of which 90% of cases are mutated within this pathway. Most recently, ∼10% of colon cancers were found to contain RSPO gene fusions, but not APC or β-catenin alterations, as an alternative mechanism of Wnt signaling activation. However, expression pattern and function of LGR4 in normal and cancer cells of human colon are largely unknown. The underlying receptor mediating the carcinogenic functions of RSPO gene fusion in colorectal cancers is also unidentified. We developed and validated a panel of LGR4 antibodies that can detect either native or denatured LGR4 with high specificity and sensitivity. Immunohistochemistry analyses were carried out in multiple matched pairs of normal and cancer tissues of human colon. In normal colon LGR4 is expressed most abundantly in epithelial cells located at the bottom of the crypts, consistent with expression data from the mouse intestine. In colon cancer, level of LGR4 is dramatically increased when compared to that of the crypt cells of the matched normal tissues. Next, we used an LGR4 antibody to isolate LGR4-high and LGR4-low cells from a colorectal cancer cell line, and compared the cell populations in rate of proliferation, migration, invasion in vitro and tumor formation and growth in xenografts. Data from these expression and functional analyses will be presented and discussed. Citation Format: Jing Yi, Wei Xiong, Xing Gong, Qingyun Liu. Expression and functional analysis of LGR4 in normal and cancer cells of human colon. [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 2714. doi:10.1158/1538-7445.AM2013-2714
FRI0247 Black Blood Mri/A for Diagnosis of Large Vessel Vasculitis
Authors: M.E. Guevara, W. Lin, M. Mossa-Basha
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Large vessel vasculitis affecting the aorta and its primary branches may present with symptoms and findings that closely mimic other diseases, making the diagnosis difficult. Conventional inflammatory markers may not provide therapeutic direction as data suggests that up to 50% of ESR/CRP measurements can be false positive in regards to disease activity. Because of the central location of the arteries involved, biopsy is generally not an option. Imaging of large vessel vasculitis is the current gold standard to confirm a diagnosis and to follow disease course. Conventional arterial imaging lacks specificity because different pathologies produce similar luminal defects and findings are not always associated with disease activity. The technique double inversion "black blood" MRI has shown value in assessment of the morphologic features of the great vessels. This technique suppresses the signal from the blood in the vessel enabling the delineation of the arterial wall from the lumen and the surrounding perivascular tissue. Furthermore, post-contrast T1 weighted sequences allow visualization of contrast enhancement of the arterial wall. Vessel wall enhancement on MRI in the setting of large vessel vasculitis has previously been assessed, but only few reports have use double inversion dark lumen techniques. <h3>Objectives</h3> The purpose of this study is to review the utility of a new imaging modality termed double inversion "black blood" MRI/A in the diagnosis and management of large vessel vasculitis. <h3>Methods</h3> We reviewed our records over the past year to identify patients with possible active large vessel vasculitis with normal values of acute phase reactants or with an inconclusive diagnosis. Data extracted included age, gender, acute phase reactants, symptoms at presentation and results of black-blood MRI/A. <h3>Results</h3> See Table 1 <h3>Outcomes</h3> Imaging confirmed a new diagnosis of vasculitis in 2 patients with normal acute phase reactants. Imaging rule out acive disease in 2 patients with history of vasculitis. Imaging identified active disease and treatment failure in 2 patients requiring a change of therapy. <h3>Conclusions</h3> Double inversion black blood MRI/A can be sensitive and specific in the diagnosis and evaluation of disease activity in large vessel vasculitis, specifically in patients with nonspecific symptoms and normal acute phase reactants. <h3>References</h3> De Souza Aw, De Carvalho, et al. Diagnosis and Calassification criteria of Takayasu arteritis. JA:8411, 2014 Yeon Hyeon, Boo Kyung, et al. Takayasu9s Arteritis: Assesment of Disease Activity with MRI/MRA. AJR:175, 2000. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3341
TCT-563 Multi-Center, First-In-Man Evaluation of the Myolimus-Eluting Bioresorbable Coronary Scaffold: 6-Month Clinical and Imaging Results
Authors: Stefan Verheye, Mark Webster, James Stewart, Alexandre Abizaid, Ricardo Costa, Jose Costa, John Yan, vinayak bhat, lynn morrison, Sara Toyloy, John Ormiston
Journal: Journal of the American College of Cardiology (2012)
OP0009 CD4+ T-Cell Differentiation by Immune Complexes and Complement
Authors: A. K. Chauhan, T. Moore
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Autoimmunity in connective tissue diseases, such as systemic lupus erythematosus (SLE) is associated with elevated levels of immune complexes (ICs), complement activation and hyperactive T cell responses. ICs activate complement, however role for ICs in modulating T-cell responses has never been explored previously. <h3>Objectives</h3> To understand the role for ICs and complement in deriving CD4<sup>+</sup> T-cell responses i.e. generation of Th1, Th17 and Tfh, CD4<sup>+</sup>effector populations. <h3>Methods</h3> Peripheral human naïve CD4<sup>+</sup> T-cells were treated in vitro with ICs and sublytic C5b-9 in the presence of anti-CD3. The activated cells were cultured under various cytokine milieu required for development of CD4<sup>+</sup> effector T-cells. Cells were phenotyped for the expression of effector T-cell markers and associated transcription factors. Flow analysis for IFN-γ, IL17A, IL-21, CXCR5, PD1, ICOS, Bcl6, and T-bet were carried out. Culture soups were analyzed for cytokines by multiplex assays. Up-regulation of FcγRIIIA and T-bet transcripts were analyzed by QT-PCR. <h3>Results</h3> Naïve CD4 cells activated with ICs and C5b-9 costimulation demonstrated the capability to differentiate into a T effector population. When cultured post stimulation in the presence of IL-2, IL-1b and IL-23, they produced IL-17A, IL-17F and IL-22. Post 48 hrs after costimulation with IC and C5b-9, we observed a three fold increase in the expression of IL-21, CXCR5 and PD1, markers of Tfh. We also observed a CD4<sup>+</sup>FcγRIIIA<sup>+</sup> population. This population did not express T-bet, a Th1 transcription factor. The ligation of FcγRIIIA by ICs resulted in receptor internalization in conjunction with IFN-γ production suggesting a new signaling pathway. <h3>Conclusions</h3> For activation of T-cell primary pep-MHC signal and costimulation from CD28 is required. All regulators of CD4<sup>+</sup> T-cells, CD28, ICOS, PD1, CTLA-4 are membrane proteins. We show a first non-membrane bound costimulator that is present at the site of tissue inflammation and tissue damage. ICs and C5b-9 successfully replaced costimulatory requirement for the development of effector Th1, Th17 and Tfh populations. We also show expression of low affinity FcγRIIIA on CD4 cells and these cells upon ligation with ICs produced IFN-γ. Naïve CD4<sup>+</sup> cells in perivascular spaces of tissues with immune deposits will thus allow localized development of effector CD4<sup>+</sup> T-cells such as Th1 and Th17 populations. Both of these cell types are known to particiapte in the development of autoimminty. <h3>Disclosure of Interest</h3> A. Chauhan Shareholder of: ProGen Biologics LLC, T. Moore: None Declared
The Role of Bone Scintigraphy in Patients With Erdheim–Chester Disease
Authors: MARTIN GOTTHARDT, ULRICH WELCKE, DÉSIRÉE BRANDT, DANIELA TONTSCH, PETER J. BARTH, JUERGEN SCHAEFER, HELMUT HOEFFKEN, KLAUS JOSEPH
Journal: Clinical Nuclear Medicine (2000)

Erdheim–Chester disease (ECD) is a rare disorder that has been reported fewer than 60 times in the literature. Although clinical findings seem to be specific at first sight, histologic classification remains unclear. It has not been decided whether ECD is part of the spectrum of histiocytoses or whether it may be a lipid storage disorder or even a primary macrophage cell disorder, although it does show a distinct histologic pattern. However, the clinical appearance alone shows several typical features, rendering the diagnosis very probable if present. This article illustrates the importance of bone scanning in ECD, because the scintigraphic pattern of involved skeletal sites may in themselves lead to the diagnosis. Several differential diagnoses are considered. The importance of bone scintigraphy as an imaging method in patients with an unclear diagnosis is discussed, as exemplary in ECD, as is its role for the detection of sites of skeletal involvement in other diseases.
Abstract 1843: Overexpression of polyisoprenylated methylated protein methyl esterase in triple negative breast cancer
Authors: Nazarius S. Lamango, Randolph Duverna, Felix Amissah, Byron J. Aguilar, Rosemary A. Poku
Journal: Cancer Research (2012)

Abstract Lack of targeted, more effective therapies for triple negative breast cancer (TNBC) has necessitated the continuous search for protein biomarkers and targets for novel therapeutic development. Polyisoprenylated monomeric G-proteins such as Ras and Rab are hyperactive in about 30% of cancers and have profound effects on cell growth. Inhibition of polyisoprenylated methylated protein methyl esterase (PMPMEase) causes the death of cancer cells thus suggesting that hyperactivity of PMPMEase may result in cancers. The current studies were to address the hypothesis that PMPMEase activity is elevated in breast cancer. PMPMEase activity was determined in breast tumors and normal adjacent tissues (NAT) in snap-frozen tissues from 10 breast cancer cases. Five- to over 20-fold increases in PMPMEase activity compared to the respective NATs were detected in 8 of the 10 cases. Specific activities ranging from 0.25 ± 0.02 to 1.58 ± 0.07 nmol/h/mg were detected in the tumors compared to 0.09 nmol/h/mg or less in the NATs. Breast cancer tissue microarrays (TMAs) consisting of 125 independent breast cancer cases and NATs were analyzed for PMPMEase expression by immunohistochemistry and scored for their immunoreactive staining intensities. Intermediate to very strong immunoreactivities were detected in the breast cancer TMA core slices compared to only trace staining in those of the NATs. The mean scores ± SEM ranged from 310 ± 21, 290 ± 7, 350 ± 15, 360 ± 18, 390 ± 14, 360 ± 29, 390 ± 13, 275 ± 10 to 65 ± 10 for TNBC, ER(+), ER(+)PR(+), ER(+)HER2(+), ER(+)PR(+)HER2(+), PR(+)HER2(+), HER2(+), PR(+) and NATs, respectively. These results show that PMPMEase overexpression in breast cancer may explain the increased enzymatic activity in the tumors. PMPMEase enzymatic activity and/or immunoreactivity may serve as diagnostic procedures for breast cancer. PMPMEase may also serve as valid target for anticancer drug development. 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 1843. doi:1538-7445.AM2012-1843
HG-17 * THE HISTONE DEACETYLASE INHIBITOR PCI-24781 SHOWS ANTIPROLIFERATIVE, PRO-APOPTOTIC AND RADIOSENSITIZING EFFECTS ON PEDIATRIC GLIOBLASTOMA CELL-LINES
Authors: P. V. Andrade, A. F. Andrade, R. G. d. P. Queiroz, C. A. Scrideli, L. G. Tone, E. T. Valera
Journal: Neuro-Oncology (2015)

The acetylation of DNA can modulate the expression of genes involved in the development and progression of malignancies. Histone deacetylase (HDACs) inhibitors are clinically active and well tolerated in the treatment of a wide variety of tumors. HDACs inhibitors can sensitize cell response to ionizing radiation, potentially reducing treatment doses and side effects. OBJECTIVES: To assess the potential radiosensitizer effect of abexinostat (PCI-24781), a new and potent pan-HDAC inhibitor in two pediatric glioblastoma cell-lines (SF188 and KNS42). METHODS: The effect of PCI-24781 on proliferation rates, clonogenic capacity and apoptosis were compared prior and following cell irradiation. The clonogenic assay was performed without irradiation (48h of incubation) at the doses of 0.25, 0.5, 1 and 2uM of PCI-24781. The clonogenic assay combined with irradiation was performed at 48h using the inhibitor IC30 for each cell-line in combination with irradiation doses of 0.5, 1, 2 and 4Gy. For cell proliferation assays, the intervals of 24h, 48h, 72h and 96h at the doses of 0.5, 1, 2, 4, 8 and 16uM of PCI-24781 were selected for study. Apoptosis were evaluated at 48h-cultures at the doses of 2, 4, 8 and 16uM. RESULTS: The HDAC inhibitor repressed cell proliferation, displaying a more significant effect at 48h in the dose of 2uM (p < 0.05). PCI-24781 also induced apoptosis (p < 0,05); the percentage of cell death for SF188 and KNS42 (at 16uM) was 40% and 55% respectively. Cells demonstrated massive decrease in colony formation with PCI-24781; this effect was more pronounced when drug was combined with irradiation (p < 0.001). CONCLUSION: These data demonstrate potential radiosensitizer and antiproliferative effects of PCI- 24781 on pediatric glioblastoma cell-lines. This study will now focus on key proteins responsible for the double-strand breaks repair caused by irradiation, trying to elucidate epigenetic pathways potentially involved in the therapy with PCI-24781. Financial Support: Fapesp (process no. 2013/15891-8).
Abstract 3589: Microbiomic analysis of colon cancer tumors and their matched normal reveals distinct gut floras.
Authors: Hassan Brim, Shibu Yooseph, Manolito Torralba, Edward Lee, Karen Nelson, Hassan Ashktorab
Journal: Cancer Research (2013)

Abstract Background: The gut flora has long been suspected to play a role in colon carcinogenesis either through their secreted toxins or through their processing of ingested nutrients leading to the production of carcinogenic products. We previously have shown that stool samples flora from patients with pre-neoplastic colon lesions differ from those from healthy individuals. However, bacteria in stool samples are not representative of the colon adherent bacteria that are more prone to affect colon mucosa homeostasis. Here we analyzed the microbiota composition in 10 colon tumors and their matched normal tissue from 10 African American patients. Materials &amp; Methods: DNA extracts from 10 pairs of colon tumors and matched normal tissue, was used to amplify the V1-V3 regions of the 16S rRNA gene. The PCR primers included the A and B adaptor sequences for 454 pyrosequencing as well as a unique 12 bp barcode incorporated onto the reverse primer such that each sample receives its own unique barcode. The amplicons were purified, quantified, normalized, and then pooled in preparation for emulsion PCR followed by 454 sequencing using Titanium chemistry. After deconvolution and trimming, the sequences were put through chimera checking (using chimera slayer). Those sequences of length &amp;gt;=100 bp that were not labeled as chimeras were then processed using RDP's classifier. Results: Overall, each tumor sample microbiota was the closest to its matched normal based on the general bacterial profile. Bacteroidetes and Firmicutes were the dominant bacterial groups in all analyzed samples. Using a Principal Component Analysis at the genus level with bacterial genera that are represented at least 5% in one sample revealed two distinctly separated healthy tissue groups, one defined primarily by Bacteroides and the second defined by Prevotella bacteria. No tumor sample was within these two groups. It is noteworthy that Fusobacteria, that was shown by other similar studies as primarily abundant in tumors, was not defining any tumor group in our study. Conclusion: Our study reveals the presence of significant microbiota changes between tumor samples and matched normal tissue even though our analysis were done only at the genus level. Further analysis at the Operational Taxonomic Units (sub-genus level) for each pair of samples are underway and will further dissect the observed differences. Citation Format: Hassan Brim, Shibu Yooseph, Manolito Torralba, Edward Lee, Karen Nelson, Hassan Ashktorab. Microbiomic analysis of colon cancer tumors and their matched normal reveals distinct gut floras. [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 3589. doi:10.1158/1538-7445.AM2013-3589
Abstract 3839: Wild-type p53 induced protein phosphatase (Wip1) inhibits the proapoptotic function of JNK and p38 MAPK in prostate cancer cells
Authors: Ji Young Song, Ji Young Park, Ga Hye Kim, Jene Choi
Journal: Cancer Research (2011)

Abstract The mechanism regulating radiation-induced anti-apoptotic response in prostate cancer cell lines is not clear yet. Wip1 is the major member of the Ser/Thr PP2C family that dephosphorylates and inactivates p38 MAPK, p53, chk1, Mdm2 and ATM. Here we provide Wip1 was negative regulator of γ-radiation-mediated apoptotic response in LNCaP cells. The levels of Wip1 were increased after exposed to γ-radiation and induced Wip1 repressed cell death. Wip1 depletion with siRNA resulted in increased apoptotic cell death in LNCaP cells, which was not observed in radiation-sensitive HeLa cells. Radiation-induced Wip1 induction was inversely co-related with the decrease of phospho-JNK and -p38 MAPK in LNCaP cells, indicating that Wip1 is a negative regulator of JNK and p38 MAPK pathways. Furthermore, in response to γ-radiation, Bax proteins are increased and directly interact with Wip1. The data suggest that Wip1 may be a central player on the mechanism of radio-resistance in LNCaP cells. Currently, we are investigating the role of Wip1 in BAX-mediated apoptotic 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 3839. doi:10.1158/1538-7445.AM2011-3839