tbuckley/cabot-search huggingface dataset:
The Growth Factor GP88 (Progranulin) Confers Aromatase Inhibitor Resistance to Breast Cancer Cells.
Authors: G. Serrero, G. Serrero, A. Brodie, A. Brodie, G. Sabnis, L. Macedo, T. Abrhale
Journal: Cancer Research (2009)

Abstract The development of aromatase inhibitors has provided novel therapeutic strategies for post-menopausal patients with estrogen receptor positive (ER+) breast tumors. Aromatase inhibitors, such as letrozole, inhibit ER+ breast cancer cell growth by blocking the synthesis of estrogen by the enzyme aromatase in the tumor stroma. However, ER+ breast cancer cases can sometimes fail or cease to benefit from such therapy. Several mechanisms have been proposed for aromatase inhibitor resistance. Here, we investigate the role of the 88 kDa autocrine growth factor PC-Cell Derived Growth Factor, also known as GP88 or progranulin on the acquisition of aromatase inhibitors resistance by ER+ breast cancer cells. GP88 is the largest member of the epithelin-granulin family characterized by a unique cysteine rich motif. GP88 has been shown to play a role in breast tumorigenesis. GP88 expression increased in breast cancer cells in a positive correlation with tumorigenesis whereas inhibition of GP88 expression lead to a 98% reduction in tumor incidence and growth rate in vivo. Pathological studies of paraffin embedded breast cancer biopsies have shown that GP88 is expressed in infiltrating ductal carcinoma (IDC) in correlation with expression of parameters of poor prognosis but was independent from Her-2 expression. Most importantly, increased GP88 expression in ER+ IDC was associated with increased recurrence and decreased overall survival. The present study investigated the effect of GP88 on the proliferation and letrozole responsiveness of ER+ breast cancer cells that express high aromatase activity (MCF-7 CA and MCF-7 AC1 cells). For both cell types, GP88 added exogenously conferred letrozole resistance in a time and dose-dependent fashion. GP88 also stimulated survival and soft agar colony formation of MCF-7-CA and AC1 cells in the presence of letrozole. GP88 overexpressing cells displayed higher basal levels of phosphorylated ERK1/2 and AKT, both known to be activated in GP88 mitogenic signaling pathways. In addition, naturally letrozole resistant breast tumors displayed a 10-fold increase in GP88 expression when compared to letrozole sensitive cells. Treatment of these letrozole resistant cells with GP88 SiRNA lead to a dose dependent inhibition of proliferation and restoration of letrozole sensitivity indicating that GP88 is regulating the ability of the cells to respond to letrozole.These data show the importance of GP88 as a target for the development of diagnostic and therapeutic products for aromatase inhibitor resistant breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4171.
Extensive cytogenetic studies of clonality following interferon-α therapy in chronic myeloid leukemia occurring in monosomic cells in a patient with Turner syndrome mosaic
Authors: A Takeshita, K Shinjo, M Yamashita, S Fujisawa, K Naito, K Ohnishi, K Takahashi, H Matsui, R Ohno
Journal: Leukemia (1999)
DRENAJE BILIAR GUIADO POR ECOENDOSCOPIA (DBUSE) FRENTE AL DRENAJE MEDIANTE COLANGIOGRAFÍA TRANSPARIETOHEPÁTICA (CTPH) TRAS CPRE FALLIDA EN LA OBSTRUCCIÓN BILIAR NEOPLÁSICA
Authors: N Alcaide, I Peñas, R Sánchez-Ocaña, M Udaondo, C De La Serna, B Velayos, L Del Olmo, P Gil, J Trueba, JM González, M Pérez-Miranda
Journal: Endoscopy (2014)

Introducción: La CTPH es el método de elección para el drenaje paliativo de la obstrucción biliar neoplásica cuando la CPRE no resulta posible. Se postula el DBUSE como alternativa a la CTPH, aunque todavía no se han comparado ambas técnicas.
S133 COPD, Occupation and Quality of Life Among Residents of a Historically Industrialised Area
Authors: LGB Lewis, A Darby, J Waterhouse, D Fishwick
Journal: Thorax (2012)

<h3>Introduction</h3> COPD is known to significantly affect health and quality of life, and is increasingly recognised to have a significant contribution from occupational exposures, particularly vapours, gases, dusts and fumes (VGDF). However, there is a paucity of evidence exploring the relationship between exposure to VGDF at work and health-related quality of life. <h3>Methods</h3> A random selection of adults aged over 55 years in the Sheffield area of the UK were mailed a self-completed questionnaire (including questions on respiratory symptoms and physician-diagnosed disease, smoking and occupational history); responders were invited to perform lung function (FEV1 and FVC), and to complete the EQ-5D-3L quality of life instrument. A measure of socioeconomic deprivation (SED), using the proportion of individuals within a participants postal code receiving income support, was also collected. <h3>Results</h3> Out of 4000 questionnaires, 2001 were returned. From these, 623 provided further data as detailed above. 57% were male, 62% had been, or were, smokers, 24% had a physician diagnosis of COPD and 62% reported having been exposed to VGDF in the past. In univariate analysis those with COPD were more likely to be older, have smoked, been exposed to VGDF and have a lower quality of life (all p&lt;0.001). A history of exposure to VGDF was associated with a lower quality of life (p&lt;0.001). Both VGDF exposure and COPD were associated with greater levels of SED (p&lt;0.001). A linear regression analysis was performed using the EQ_5D summary index as the dependant variable and age, gender, SED, smoking status, physician diagnosed COPD and percentage predicted FEV1 and VGDF exposure as independent variables. Female gender, greater SED, VGDF exposure and physician diagnosed COPD were identified as predictors of reduced quality of life (as measured by EQ-5D VAS and summary index scores). <h3>Discussion</h3> These results support the link between COPD and reduced quality of life, and additionally provide evidence to link occupational exposures to VGDF to a reduction in quality of life. These findings are of significance to health care professionals and policy makers, given future expectations for longer working lives.
Abstract 4961: In human breast cancer cells thyroid hormone signaling overshadows estrogen signaling on SMP30 gene leading to induction of apoptosis
Authors: Sandip K. Mishra, Pranati Sar, Bandita Rath, Dharmendra Bhargava, Debomita Sengupta, Sanjib Chaudhary
Journal: Cancer Research (2012)

Abstract Crosstalk between thyroid and estrogen hormones actions have been documented with regard to a variety physiological functions. Both of these hormones regulate transcription of target genes by binding to their nuclear receptors that interact with specific responsive elements (estrogen and thyroid hormone response elements, i.e. ERE and TRE, respectively. Recently, we have demonstrated that 3, 3′5 Triiodo L Thyronine (T3) can induce apoptosis in ER+ve highly metastatic breast cancer MCF-7 cells through downregulating Senescence marker protein-30 (SMP30) gene. SMP30 has also been reported to be downregulated by 17β-Estradiol (E2) in prostrate gland and mammary epithelial cells. Interestingly, thyroid receptors (TRs) and estrogen receptor (ER) share a common response element, so we hypothesised a possible competition between both the receptors in SMP30 promoter under different hormone responses. To prove this hypothesis, gel retardation and luciferase assays were conducted by taking hSMP30 promoter reporter construct validated our findings of the putative ERE site. Competition Chromatin immunoprecipitation assay (ChIP) showed prominent TRβ binding irrespective of thyroid and estrogen hormone treatment. As a result, there was a significant repression found in whole promoter activity in presence of T3 and also in presence of both E2 and T3 treatment. Although the SMP30 promoter activity was same in response to E2 and T3 but the functional consequences after downregulation of SMP30 in human breast cancer cells were different. Overall our studies indicate that estrogen signalling/downstream target molecules of E2 weren't affected by estrogen mediated SMP30 downregulation however, SMP30 downregulation by thyroid hormone synergized the effect of T3 by further inducing apoptosis in human breast cancer cells. Thyroid hormone induced apoptosis in human breast cancer cells was through activated p53 molecule. 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 4961. doi:1538-7445.AM2012-4961
P106Loss of myocardial nNOS in human atrial fibrillation (AF) shortens action potential duration (APD) by increasing Ito: Implications for AF-induced electrical remodelling
Authors: X Liu, S Reilly, R Carnicer, A Recalde, G Krasopoulos, R Sayeed, R Desilva, B Casadei
Journal: Cardiovascular Research (2014)

Purpose: Understanding the mechanism underlying atrial electrical remodelling in AF is of fundamental importance for the prevention and treatment of AF. We have recently found that neuronal nitric oxide synthase (nNOS) activity is dramatically reduced in atrial myocytes from patients with AF. Whether loss of nNOS activity contributes to AF-induced atrial electrical remodelling remains to be established. Methods: Whole-cell patch clamp was used to record action potentials (APs) and ion currents in human and murine right atrial myocytes. AF was induced in isoflurane anaesthetised mice by using trans-oesophageal electrical stimulation. N=number of patients or mice, n= number of myocytes. Results: Inhibition of nNOS by S-methylthiocitrulline (SMTC, 100 nM), induced a significant reduction in APD at 20 (38%), 50 (39%) and 90 (30%) percent of repolarization in atrial myocytes from patients in sinus rhythm (SR, N=8, n=38 control vs. N=8, n=31 in the presence SMTC, p<0.001) and suppressed APD rate-dependent adaptation (from 0.5 to 3 Hertz, N=6, n=24 control vs. N=6, n=17 cells with SMTC, p<0.05). In mice, nNOS inhibition or gene deletion reduced APD50 by 46% and 29%, respectively. (N=9, n=35 from nNOS-/- & N=6, n=11 WT plus SMTC vs. N=10, n=28 WT control, p<0.001 for the effect of nNOS dysruption). By contrast, SMTC had no effect on APD in atrial myocytes from patients with AF or nNOS-/- mice. In agreement with these findings, nNOS-/- mice displayed a 2-fold increase in AF inducibility in response to burst stimulation (p<0.05 vs. WT littermates, N=18 per genotype). Investigations of the ionic changes underlying the effect of nNOS dysruption on APD in RA myocytes from patients in SR (N=7, n=31 control vs. N=7, n=35 in SMTC) or WT mice with SMTC (N=9, n=19 control via N=6, n=9 in SMTC) showed an increase in Ito with SMTC in both species with no change in IK1 or IKr. Ito blockade with 4-AP (0.5 mM) significantly prolonged APD20 (by 19% in SR and by 153% in SMTC), APD50 (by 19% in SR and by 55% in SMTC) and, to a lesser extent, APD90 (by 7% in SR and by 13% in SMTC) in atrial myocytes from patients in SR. 4-AP also recovered the APD rate dependent adaptation that was suppressed by SMTC, confirming a role of Ito in the nNOS regulation of APD in human atrial myocytes. Conclusions: In mammalian atrial myocytes, nNOS-derived NO plays an important role in the regulation of APD and its rate-dependent adaptation by modulating Ito. These findings suggest that the marked loss of nNOS protein and activity in the fibrillating atrial myocardium has potentially important implication for AF-induced electrical remodelling.
Long-term prognosis of asthma, chronic obstructive pulmonary disease, and asthma-chronic obstructive pulmonary disease overlap in the Copenhagen City Heart study: a prospective population-based analysis
Authors: Peter Lange, Yunus Çolak, Truls Sylvan Ingebrigtsen, Jørgen Vestbo, Jacob Louis Marott
Journal: The Lancet Respiratory Medicine (2016)
Incidental Detection of Primary Breast Carcinoma with a Modified Coincident Camera in a Patient with Non-Hodgkin’s Lymphoma and Melanoma
Authors: Michelle L Pohland, Judith M Joyce, Daniel T Myers, Sigurdur R Petursson
Journal: Clinical Nuclear Medicine (2002)

POHLAND, MICHELLE L. M.D.*; JOYCE, JUDITH M. M.D.*; MYERS, DANIEL T. M.D.*; PETURSSON, SIGURDUR R. M.D.† Author Information
Adénome festonné et polype hyperplasique du côlon: caractérisation et critères de différenciation en endomicroscopie confocale, étude de validation
Authors: S Leblanc, F Cholet, J Le Meur, L Doucet, B Terris, J Jezequel, S Chaussade, M Robaszkiewicz, F Prat
Journal: Endoscopy (2012)

Les adénomes festonnés (AF), représentant des lésions prénéoplasiques impliquées dans la voie festonnée de cancérogenèse colique, doivent être réséqués endoscopiquement. Mais leur présentation, proche des polypes hyperplasiques (PH), rend leur identification difficile. L'endomicroscopie confocale, en permettant des «biopsies optiques», pourrait être intéressante pour différencier PH et AF. Une première étude originale* a identifié des critères de différenciation des PH et AF, en utilisant l'endomicroscopie confocale par mini-sondes (ECM) par système Cellvizio® (Mauna Kea Technologies, Paris, France).
P485 THE RATIO OF ASCITES CALPROTECTIN TO TOTAL PROTEIN IS A DIAGNOSTIC AND PROGNOSTIC MARKER FOR SPONTANEOUS BACTERIAL PERITONITIS IN LIVER CIRRHOSIS
Authors: P. Lutz, K. Pfarr, H.-D. Nischalke, B. Krämer, F. Goeser, J. Nattermann, T. Sauerbruch, A. Hoerauf, C.P. Strassburg, U. Spengler
Journal: Journal of Hepatology (2014)
Abstract 1883: 2-Hydroxyglutarate: A candidate oncometabolite in breast cancer.
Authors: Prachi Mishra
Journal: Cancer Research (2013)

Abstract Recent work in our laboratory identified a poor outcome tumor subtype with a high tissue 2HG concentration, distinct genome-wide DNA methylation, and a stem cell-like transcriptional signature. Currently, we do not know the origin of 2HG in these tumors but ruled out that it is caused by acquired isocitrate dehydrogenase mutations. Tumors with high 2HG tended to be estrogen receptor (ER)-negative and were over-represented among the African-American patients. Additional investigations revealed that 2HG can accumulate in a subset of human breast cancer cell lines to 50- to 100-fold above the baseline in non-cancerous cells, reminiscent of the difference between 2HG-high tumors and their adjacent non-cancerous tissue. The majority of the 2HG-high cell lines showed basal-like characteristics. While some cancer cells had these highly increased 2HG levels, other cell lines did not accumulate 2HG, providing a model to study 2HG treatment effects in cell lines with low endogenous 2HG and to identify the origin of increased 2HG production in those cell lines with high endogenous 2HG. Thus, we tested the hypothesis that 2HG influences breast cancer phenotypes. These experiments showed that 2HG induced phenotypic alterations, DNA methylation pattern alterations, proliferation, increased invasion and migration, and EGFR pathway activation in breast epithelial cells consistent with its oncogenic function in breast cancer. However, the observed phenotypes were partly cell line- and dose-dependent in our short term assays. Our results also indicated that different subtypes of breast cancer cells may respond differentially to 2HG, which suggests that possibly different cellular pathways are activated by 2HG in the various subtypes. Citation Format: Prachi Mishra. 2-Hydroxyglutarate: A candidate oncometabolite in breast 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 1883. doi:10.1158/1538-7445.AM2013-1883
18F-FDG PET/CT Findings in Multicentric Reticulohistiocytosis
Authors: Bing Zhang, Hui Zhou, Jiande Han, Xinchong Shi, Xiangsong Zhang
Journal: Clinical Nuclear Medicine (2015)

Multicentric reticulohistiocytosis is a rare systemic inflammatory disease of unknown etiology characterized by the infiltration of histiocytes and multinucleated giant cells into multiple systems. The definitive diagnosis depends on biopsy of the affected tissues. Here, we report the F-FDG PET/CT findings of a 62-year-old man with multicentric reticulohistiocytosis. Increased FDG uptake was observed in cutaneomucosal papules, surrounding tissues of many joints, multiple muscles, and lymph nodes.
New Cancer Genes Crowd the Horizon, Create Possibilities
Authors: D. Holzman
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article New Cancer Genes Crowd the Horizon, Create Possibilities Get access David Holzman David Holzman Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 15, 2 August 1995, Pages 1108–1110, https://doi.org/10.1093/jnci/87.15.1108 Published: 02 August 1995
Abstract 1222: Simultaneous detection of 30 cytokines in human sera using barcoded magnetic bead technology.
Authors: Aiguo Zhang, Rachel Chuang, Lily Chen, XiNing Zhu, Rachel Diaz, Dean Tsao
Journal: Cancer Research (2013)

Abstract Cytokines mediate a wide range of physiological responses including immunity, inflammation, and hematopoiesis, which are important circulating proteins. It has been well demonstrated that cytokines are associated with a spectrum of diseases ranging from tumor growth to infection and to Parkinson. Traditionally, cytokines are measured by immunoblot or immunoassay, which are both time consuming and not cost effective. There is an increasing need for multiplexing assays in this field. With the development of bead array technology, which uses fluorescent color-coated microspheres analyzed with a dedicated reader, simultaneous detection of multiple analytes becomes possible in a single well of a microtiter plate. Although the bead array technology becomes more and more popular and dominated in the multiplexing assay market, there are still some limitations and potential issues from this technology, such as photobleaching of the fluorescent color-coated beads and expensive laser detector. Recently, a new generation of the reader has been developed, which replaces laser detector with CCD camera. However, it still uses fluorescent color-coated beads, which makes the assay sensitive to light and unstable. Here we present a new Barcoded Magnetic Bead technology, which employs a permanent bar code on magnetic beads with high resolution CCD camera for scanning. This technology has successfully solved the problems from fluorescent color-coated bead and makes the multiplex assay much more stable and reliable. We can detect 30 cytokines from human sera with limit of detection less than 5 pg/ml, while inter- and intra assay CV less than 10%. The results are correlated very well with the bead array technology and traditional ELISA. In addition, our multiplex protein assays have unique internal control in each sample well, which makes the assay much more reliable and robust. This multiplex technology can be used in both life science research and clinical fields. Citation Format: Aiguo Zhang, Rachel Chuang, Lily Chen, XiNing Zhu, Rachel Diaz, Dean Tsao. Simultaneous detection of 30 cytokines in human sera using barcoded magnetic bead technology. [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 1222. doi:10.1158/1538-7445.AM2013-1222
P28 Defective T-regulatory function in autoimmune hepatitis may partially derive from a pro-inflammatory skewing of Gal9+T-regs
Authors: R. Liberal, G. Mieli-Vergani, D. Vergani, M. S. Longhi
Journal: Gut (2011)

<h3>Introduction</h3> In autoimmune hepatitis (AIH) CD4<sup>+</sup>CD25<sup>+</sup> regulatory T-cells (T-regs) are defective in their ability to control CD4 T-cell effector function. T-regs express Galectin9 (Gal9), a β-galactosidase-binding-protein that inhibits Th1-mediated immune-responses by binding the T-cell-immunoglobulin-and-mucin-domain3 (Tim-3) on CD4 effector cells. In AIH T-regs express reduced levels of Gal9. <h3>Aim</h3> To characterise lineage-specific transcription factor and cytokine profiles of peripheral-blood-derived Gal9<sup>+</sup> T-regs in AIH. <h3>Method</h3> 34 ANA/SMA+ patients (24 females; median age: 14.6 years) and 17 healthy subjects (HS, 12 females, median age: 29 years) were studied. The phenotype of circulating T-regs was determined by cytofluorimetry using CD4, CD25 and CD127 monoclonal antibodies. The frequency of cells positive for Gal9, FOXP3, T-bet, GATA3 and RORC and that of cells producing IFNγ, IL-10, TGF-β and IL-17 were determined by intracellular staining. T-reg suppressor function was evaluated in a proliferation assay following co-culture with CD25<sup>-</sup>Tim-3<sup>+</sup> and CD25<sup>-</sup>Tim-3<sup>−</sup> autologous target cells. <h3>Results</h3> Within Gal9<sup>+</sup> cells the frequency of: (1) FOXP3<sup>+</sup> cells was lower in AIH than in HS (14.4±2 vs 42.8±3.1, p&lt;0.001); (2) T-bet<sup>+</sup>, GATA3<sup>+</sup> and RORC<sup>+</sup> cells was similar in AIH and HS; (3) IL-10-producing cells was lower in AIH than in HS (5.1±0.6 vs 9.1±0.5, p&lt;0.001) but higher than in the Gal9<sup>−</sup> T-reg fraction for both (AIH: 5.1±0.6 vs 2.3±0.2, p=0.001; HS: 9.1±0.5 vs 3.3±0.4, p&lt;0.001); (4) TGF-β-producing cells was lower in AIH than in HS (6.4±0.7 vs 8.1±0.4, p=0.04); (5) IFNγ- and IL-17-producing cells was higher in AIH than in HS (IFNγ: 4.4±0.6 vs 2.1±0.3, p=0.002; IL-17: 4.1±0.6 vs 1.8±0.2, p=0.002). Treatment with anti-IL-10 neutralising antibodies reduced T-reg ability to suppress CD25<sup>-</sup>Tim-3<sup>+</sup> cell proliferation (AIH: 42% inhibition in the absence of antibodies vs 36% in their presence, p=0.06; HS: 56% vs 48%, p=0.04), while did not affect CD25<sup>−</sup>Tim-3<sup>−</sup> cell proliferation. <h3>Conclusion</h3> A skewing towards a pro-inflammatory phenotype and a reduced proportion of FOXP3<sup>+</sup> and IL-10-producing cells within Gal9<sup>+</sup> T-regs may contribute to defective immunoregulation in AIH. The reduction of Gal9<sup>+</sup>T-reg suppression following anti-IL-10 blockade both in health and AIH, suggests a role for IL-10 in Gal9<sup>+</sup>T-cell immune-regulatory function.