tbuckley/cabot-search huggingface dataset:
Abstract 2441: CHI3L1 in allergic pulmonary inflammation promotes breast cancer metastasis by upregulation of MMP-9
Authors: Stephania Libreros, Ramon Garcia-Areas, Vijaya L. Iragavarapu-Charyulu
Journal: Cancer Research (2011)

Abstract Disseminated metastasis is one of the main causes of malignancy related deaths in breast cancer patients. Murine mammary tumors cells metastasize to the lung 5 weeks post tumor-implantation. However, in the presence of asthma, metastasis is seen at an earlier time point. In this study, we investigated the molecule(s) contributing to early metastasis. One of the common molecules among asthma and breast cancer is a glycoprotein known as chitinase-3-like-1 (CHI3L1) which induces TH2 proinflammatory cytokines and matrix degrading enzymes. The expression of CHI3L1 is elevated in the lungs and serum of asthmatic patients and correlates with disease severity. Interestingly, this glycoprotein is also elevated in plasma of patients with metastatic breast cancer. Using murine mammary cancer models, we show the link between increased metastasis and asthma. The pathways that tumor cells use for metastasis have significant similarities with the mechanisms mediating allergen-induced leukocyte recruitment. Thus, leukocyte recruitment to the site of inflammation and tumor cell metastasis involves extracellular matrix degradation. Matrix metalloproteinase-9 (MMP-9) is one such enzyme that can degrade all aspects of the extracellular matrix. Our previous studies have shown increased levels of MMP-9 in mammary tumor-bearing mice. MMP-9 has been reported to be upregulated in the presence of CHI3L1. In this report, we show that the levels of CHI3L1 are higher in asthmatic tumor bearers compared to either tumor controls or asthma controls. We hypothesize that the elevated CHI3L1 expression causes increased MMP-9 production leading to higher metastasis. To answer this hypothesis, a mouse model of allergic pulmonary inflammation and two types of well-established metastatic mammary tumor models were used. Analysis of serum, bronchioalveolar lavage (BAL), lung and spleen by RT-PCR and ELISA revealed higher expression of CHI3L1 in asthmatic tumor bearers. In summary, these studies implicate a relationship between allergic pulmonary inflammation and increased breast cancer metastasis to the lung. As CHI3L1 is involved in both of these diseases, this molecule may be a novel target for suppressing/preventing metastasis. 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 2441. doi:10.1158/1538-7445.AM2011-2441
P4-01-20: Specific Anti-Proliferative Profile of Endoxifen for MCF-7 Cell Compared to 4-OH Tamoxifen.
Authors: S Saji, M Hirose, S-I Hayashi, K Kuroi
Journal: Cancer Research (2011)

Abstract Background: Endoxifen and 4-hydroxy tamoxifen are both active metabolites of tamoxifen and exert anti-tumor activity for ER+ breast cancer. However, only small numbers of paper reported biological profile of endoxifen. Methods: Cells were incubated with various concentration of endoxifen ( (Z)-4-Hydroxy-N-desmethyl Tamoxifen (&amp;lt;10% with (E)-form)) for 6 days and viability (anti-proliferative index) was assessed by cell counting kit-8. For seeking the influence of ERβ, two independent ERβ expressing clones of MCF-7 cells were established by stable transfection of ERβ vesctor to MCF-7. Western blotting was done with ERα, ERβ, PgR and HER2 antibodies. Results: IC50s of endoxifen for MCF-7 were 100 nM in estradiol (E2) deprivation condition and 500 nM in the presence of 1nM E2. These are significantly higher than those of 4-OH tamoxifen, which are 10 nM without E2 and 50 nM with E2, respectively. From the previous reports, plasma endoxifen concentrations in breast cancer patients were ranged from 20 to 200 nM according to CYP2D6 phenotype. Anti-proliferative index of 20 nM endoxifen for MCF-7 was 0.7 (indicating 30% reduction in proliferative activity), and 200 nM endoxifen was 0.5 in the absence of E2. These were 0.95 (20 nM) and 0.75 (200nM), respectively, when incubated with 1 nM E2. 10 nM 4-OH tamoxifen, which is mean concentration in patient plasma, showed about 0.6 anti-proliferative index with no regards to E2 condition. Without E2, endoxifen reduced ERα expression as previously reported, however, endoxifen increased ERα amount in the presence of E2 accompanied with decrease of HER-2 expression. This alternation of ERα and HER2 expression were identical to those observed using 4-OH tamoxifen. There was a weak tendency that ERβ expressing MCF-7 clones showed favorable response to endoxifen compared to parent MCF-7, but this was not significant. Conclusion: Endoxifen is active agent for MCF-7 cell, however, it requires 10-fold higher concentration compared to 4-OH tamoxifen to achieve IC 50. Difference of anti-proliferative effect between 20 nM and 200 nM of endoxifen are relatively small, and it might result in minor difference for clinical response, as expected from recent clinical studies of CYP2D6. This is the first time to show that endoxifen has opposite effect to ERα protein level depending on the presence or absence of E2. ERβ expression did not enhance activity of endoxifen in contrast to previous report. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-01-20.
COMPARISON BETWEEN CENTRAL CLINICAL EVENTS CLASSIFICATION COMMITTEE AND SITE INVESTIGATOR ASSESSMENT OF CLINICAL OUTCOMES: INSIGHTS FROM THE NAVIGATOR TRIAL
Authors: Maria Cecilia Bahit, Abhinav Sharma, Jie-Lena Sun, Laine Thomas, Steven Haffner, Rury Holman, Renato Lopes
Journal: Journal of the American College of Cardiology (2016)
Endoscopic and radiologic appearance of giant esophageal hemangioma
Authors: Yang-Yuan Chen, Chih-Ming Lin, Yung-Fang Chen
Journal: Endoscopy (2015)

A 38-year-old man presented to our hospital with long-term palpitations and acid regurgitation. A previous endoscopy at another clinic had led to the impression that esophageal varices were present.
E2-2 Protein and Fuchs's Corneal Dystrophy
Authors: Keith H. Baratz, Nirubol Tosakulwong, Euijung Ryu, William L. Brown, Kari Branham, Wei Chen, Khoa D. Tran, Katharina E. Schmid-Kubista, John R. Heckenlively, Anand Swaroop, Goncalo Abecasis, Kent R. Bailey, Albert O. Edwards
Journal: New England Journal of Medicine (2010)

Fuchs's corneal dystrophy (FCD) is a leading cause of corneal transplantation and affects 5% of persons in the United States who are over the age of 40 years. Clinically visible deposits called guttae develop under the corneal endothelium in patients with FCD. A loss of endothelial cells and deposition of an abnormal extracellular matrix are observed microscopically. In advanced disease, the cornea swells and becomes cloudy because the remaining endothelial cells are not sufficient to keep the cornea dehydrated and clear. Although rare genetic variation that contributes to both early-onset and typical late-onset forms of FCD has been identified, to our knowledge, no common variants have been reported.We performed a genomewide association study and replicated the most significant observations in a second, independent group of subjects.Alleles in the transcription factor 4 gene (TCF4), encoding a member of the E-protein family (E2-2), were associated with typical FCD (P=2.3x10(-26)). The association increased the odds of having FCD by a factor of 30 for persons with two copies of the disease variants (homozygotes) and discriminated between case subjects and control subjects with about 76% accuracy. At least two regions of the TCF4 locus were associated independently with FCD. Alleles in the gene encoding protein tyrosine phosphatase receptor type G (PTPRG) were associated with FCD (P=4.0x10(-7)), but the association did not reach genomewide significance.Genetic variation in TCF4 contributes to the development of FCD. (Funded by the National Eye Institute and others.)
Abstract 5009: Identification of DNA methyltransferase target sites in cancer cells
Authors: Rochelle L. Tiedemann, Keith D. Robertson
Journal: Cancer Research (2012)

Abstract Aberrant DNA methylation is commonly observed in cancer and is characterized by genome-wide hypomethylation and gene-specific hypermethylation, which is thought to contribute to genomic instability and tumor suppressor gene silencing, respectively. The DNA methyltransferases (DNMTs) are responsible for the establishment (DNMT3A, DNMT3B, DNMT3L) and maintenance (DNMT1) of DNA methylation patterns genome-wide. The mechanism by which DNA methylation patterns are altered in cancer is not well understood. Genome-wide unique and overlapping target sites for each of the DNMTs are also unknown both in normal and cancer states. Identification of DNMT target loci is essential in order to better understand how aberrant DNA methylation occurs in cancer. To study this process, DNMT mRNA levels were depleted both individually and in a combinatorial fashion via RNAi-based techniques in embryonic carcinoma cells. Following reduction in DNMT expression, the resulting DNA and RNA was analyzed for genome-wide DNA methylation and gene expression patterns, respectively. An affinity purification method, Methyl-Binding Domain (MBD)-seq, was used to capture and enrich methylated regions of the genome by utilizing the methyl-binding domain of MBD2b. The enriched methylated DNA was then used to construct an Illumina sequencing library. Global gene expression patterns were analyzed by microarray for each RNA sample. Next generation sequencing and microarray data were analyzed using several available algorithms (e.g. MACS) and high-throughput data software packages (e.g. Partek Genomics Suite) in order to construct and evaluate the DNA methylation profiles and subsequent gene expression changes that result from DNMT depletion. Our data show that distinct changes in DNA methylation profiles occur among the various DNMT knockdown samples that permit us to identify unique and cooperative target loci for each DNMT. Further elucidation of DNMT target sites holds great promise for enhancing our understanding of mechanisms that control aberrant DNA methylation that is observed in cancer as well as provide insight and rationale for targeting specific DNMTs in cancer therapies. 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 5009. doi:1538-7445.AM2012-5009
HACIA UN NUEVO MODELO DE PREPARACIÓN EN LA CAPSULOENDOSCOPIA DE COLON.
Authors: C Gutiérrez González, I Gutiérrez Domingo, A Alcalde Vargas
Journal: Endoscopy (2012)

Introducción y objetivos: Hasta ahora, el uso de la capsuloendoscopia de colon (Pillcam Colon 2) se ha visto limitado por deficiencias en la preparación. Realizamos un estudio piloto para determinar la eficacia de una nueva preparación, basada en la asociación de Prucaloprida (Resolor) y polietilenglicol (Moviprep). El objetivo es mejorar la limpieza intestinal y aumentar las tasas de expulsión en tiempo, aumentando así la rentabilidad, con una nueva preparación que evita la toma de Fosfosoda y Domperidona con sus efectos adversos y contraindicaciones. Material y método: Estudio piloto con 10 pacientes (casos) con la nueva preparación, comparados con 40 pacientes control con la preparación estándar. Evaluamos el grado de limpieza según la escala de Tarquinia y los tiempos de tránsito gástrico, intestinal y colónico, además de la tasa de expulsión a tiempo. Valorado por dos investigadores distintos. Protocolo de preparación: -Dos días de dieta sin residuos-Día antes de la prueba, dieta líquida-Resolor 2mg, 1 cada día de la dieta y 2 el día de la exploración-Moviprep, 1 litro la tarde antes y 1 litro en la mañana de la exploración-Después 2 boosters en las alarmas 1 y 2 de medio litro Moviprep cada uno. Resultados: Cohorte con 18 hombres y 36 mujeres, con edad media de 54,7 años (14–82). Preparación adecuada en el 100% de los casos por el 45% en los controles (p=0,009). Tasa de expulsión en tiempo del 90% en los casos por un 67,5% en los controles (p=0,057). Se acortaron los tiempos medios de tránsito gástrico (74.9 vs. 41 minutos; p=0,092) intestinal (79 vs. 34 minutos; p=0,001) y colónico (261 vs. 228 minutos; p=0.49). Ninguna complicación asociada a la nueva preparación. Conclusiones: La mayor limpieza del colon así como el acortamiento del tránsito intestinal sin acelerar el del colon con la nueva preparación (Prucaloprida+Polietilenglicol), permite realizar un estudio del colon de mayor calidad.
Radiosurgical endoscopy: fluoro-endoscopically guided percutaneous placement of a catheter for drainage of a complicated intrathoracic anastomotic septic collection
Authors: Teresa Staiano, Federico Buffoli
Journal: Endoscopy (2014)

An 84-year-old man underwent abdominothoracic esophagectomy with gastric pull-up and an intrathoracic stapled anastomosis for advanced cancer of the cardia with involvement of the distal esophagus. A contrast study at 1 week after surgery detected anastomotic leakage. Endoscopy showed intermediate anastomotic leakage ([Fig. 1]), and a 23 × 125-mm WallFlex FC stent (Boston Scientific, Natick, Massachusetts, USA) was placed [1]. A persistent purulent efflux from the chest drains was observed, and computed tomography (CT) revealed a 30 × 20-mm encapsulated peri-anastomotic septic collection in the mediastinum. The stent was checked for migration and removed, and a persistent small leak was detected ([Fig. 3 a]). Because of continued contamination of the mediastinum through the leak, adequate drainage of the peri-esophageal mediastinum was needed, with endoscopic closure of the dehiscence. Under fluoroscopic control and endoscopic guidance, a hydrophilic guidewire was advanced percutaneously and grasped with a snare inserted endoscopically through the esophageal side of the fistula into the collection ([Fig. 2 a]). A biliary balloon catheter was passed through the scope into the cavity, and the percutaneous access to the collection was dilated to 10 mm ([Fig. 2 b]). A 10.2-Fr drainage catheter was placed on the guidewire and advanced through the skin into the collection and left in situ for 4 weeks ([Fig. 2 c], [Video 1]) [2] [3]. The adequacy of percutaneous drainage was assessed with CT ([Fig. 3 d]). The anastomotic residual leak was closed endoscopically by inserting Vicryl mesh with fibrin glue ([Fig. 3 b, c]) [4]. Complete healing was achieved after three treatment sessions. The catheter was removed when the daily output diminished to less than 10 mL/d. CT at 4 weeks showed stranding in the region of the previous collection without recurrence.
Abstract 1058: E-cadherin mutations contribute to gastric carcinogenesis by modulating multiple EGFR-dependent downstream signaling pathways
Authors: Stefan Heindl, Christina Lang, Claudia Böllner, Katharina Malinowsky, Karl- Friedrich Becker, Birgit Luber
Journal: Cancer Research (2010)

Abstract Mutations in the gene encoding the cell adhesion molecule E-cadherin and overexpression of the epidermal growth factor receptor (EGFR) represent fundamental genetic alterations associated with diffuse-type gastric cancer. Mutations, e.g. in frame deletion of exon 8 (del 8), lead to loss of putative extracellular Ca2+-binding sites of E-cadherin, thereby impairing its functionality. Several studies have shown a bidirectional crosstalk between E-cadherin and EGFR. Functional wild-type (wt) E-cadherin inhibits ligand-induced EGFR activation, but mutations lead to a loss of its suppressive function, resulting in increased EGFR activation and recruitment of downstream signalling components. The phenotype of cells harboring such mutations is characterized by increased proliferation and elevated migratory and invasive potential. Our project aims at studying the impact of somatic mutations of E-cadherin on EGFR-mediated signalling pathways, in order to identify signalling molecules of these pathways as molecular targets for selective therapies in gastric cancer. Cell lines expressing wt or mutant E-cadherin (del 8) were EGF-stimulated and cellular lysates were analyzed by commercial proteome profiler antibody array (R&amp;D Systems). The array allowed detection of the phosphorylation status of 48 signalling molecules and facilitated identification of differential activation. We found differential response to EGF stimulation of proteins involved in DNA damage and repair, such as p53 and CHK2, in both cell lines. As both proteins are tumorsuppressors, their dysfunction could contribute to tumor progression. Furthermore, Src-family kinases (SFKs) like Src, Yes, Fgr, Lck and Lyn exhibited different activation profiles in response to EGF-stimulation in both cell lines. As SFKs are key players in multiple cellular processes like cell growth, differentiation, cellular adhesion, migration and invasion, the impact of their differential activation on the cellular phenotype is subject of ongoing experiments. To determine the role of the identified targets in gastric carcinogenesis and the mechanisms of crosstalk between E-cadherin and EGFR a protein microarray platform was established, allowing analysis of multiple samples under the same experimental conditions. This approach will reveal new insights in EGFR-mediated signalling pathways contributing to gastric carcinogenesis and complete our data describing how tumor associated mutations of E-cadherin affect cellular signalling. 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 1058.
A Five-Year Study of the Incidence of Dyskinesia in Patients with Early Parkinson's Disease Who Were Treated with Ropinirole or Levodopa
Authors: Olivier Rascol, David J. Brooks, Amos D. Korczyn, Peter P. De Deyn, Carl E. Clarke, Anthony E. Lang
Journal: New England Journal of Medicine (2000)

There is debate about whether the initial treatment for patients with Parkinson's disease should be levodopa or a dopamine agonist.
SP0060 Spondyloarthritis/ankylosing spondylitis drug therapy
Authors: J. Braun
Journal: Annals of the Rheumatic Diseases (2013)

Ankylosing spondylitis (AS), the major subtype and a major outcome of an interrelated group of rheumatic diseases named spondyloarthritides (SpA), is part of the subgroup with predominant axial symptoms that is now named axial SpA (axSpA), the other part non-radiographic axial SpA. The most important clinical symptom of axSpA is inflammatory back pain (IBP), asymmetric oligoarthritis, enthesitis, and anterior uveitis, there are close associations with psoriasis and chronic inflammatory bowel disease (IBD). The outcome is mainly influenced by the degree of disease activity over time and the loss of function and mobility, part of which is caused by inflammation, while the other part is due to new bone formation in the spine and structural damage of peripheral joints, the latter mainly in PsA. Male patients have more radiographic progression. Non-steroidal anti-inflammatory agents (NSAIDs) are currently considered first choice of medical therapy. NSAIDs are widely used to ameliorate spinal pain but there is growing evidence that they may also inhibit syndesmophyte growth. There is a clear role for regular physiotherapy in AS to prevent loss of spinal mobility. There are now 4 anti-TNF agents approved for the treatment of patients with active AS who have insufficiently responded to conventional therapies: infliximab, etanercept, adalimumab and golimumab. TNF blockers seem to have no influence on new bone formation in AS but they do inhibit radiographic damage in PsA. While the efficacy of anakinra, rituximab, abatacept, sarilumab and tocilizumab has not been convincingly shown in AS, the anti-IL-17a antibody secukinumab may work in this indication. <h3>Disclosure of Interest</h3> None Declared
SELLADO ENDOSCÓPICO DE DEHISCENCIAS, FÍSTULAS Y PERFORACIONES MEDIANTE PROTESIS AUTOEXPANDIBLES
Authors: C Loras, JB Gornals, JC Espinós, C Pons, JM Botargues, JM Nogueira
Journal: Endoscopy (2011)

Introducción: el uso de las prótesis esofágicas más habitual y extendido es en la paliación de disfagia en pacientes con cáncer de esófago. Su utilización en el sellado de dehiscencias, fístulas o perforaciones es más novedoso y poco reportado.
Abstract 631: Androgen receptor(AR) splice variants inhibit responses to IGF-IR inhibition in prostate cancer
Authors: Shihua Sun, Kathleen Haugk, Robert L. Vessella, Holly Nguyen, Kathryn Soriano, Stephen R. Plymate
Journal: Cancer Research (2010)

Abstract Constitutively active splice variants of the androgen receptor (AR) are frequently expressed (59% of metastases) following castration in prostate cancer patients and are associated with earlier tumor recurrence compared to tumors containing only wild-type (wt) AR. In most tumors the variant is expressed along with wt-AR. When wtAR and variant AR are expressed in cells following castration there is a marked decrease in IGF type 1 receptor expression (IGF-IR), an AR target whose expression is increased by wtAR. In order to understand these findings we expressed the AR splice variant in which exons 5, 6, and 7 are skipped during AR splicing resulting in constitutively active ARv567es along with wtAR in a prostate cancer cell line not expressing AR, M12, as well as ARv567es in AR positive LnCaP cells. In both lines ARv567es was found only in the nucleus in the absence of ligand but wtAR had also been transported to the nucleus and absolute levels of AR protein were increased in the absence of ligand in cells expressing the variant. The increase in wtAR protein is due to decreased degradation of wtAR associated with ARv567es. When ligand was added, PSA response was increased 5-fold over cells transfected only with wtAR. Further, whereas transfection with wtAR enhances IGF-IR expression and response to IGF-I ligand, in the presence of ARv567es IGF-IR expression in response to IGF-I was suppressed. When ARv567es was HA tagged and expressed along with wtAR pull-down of ARv567es with HA resulted in concomitant precipitation of wtAR. Subsequent deletion analysis of ARv567es demonstrated direct binding between the two ARs in specific cystine-rich domains. Further, wtAR-induced IGF-IR expression is a non-genomic AR cytoplasmic action through binding to src and MAPK phosphorylation. Although ARv567es binds src, phosphorylation of MAPK does not occur. Finally, when LnCaP cells expressing ARv567es were grown sc with MatrigelTM in immuno-compromised mice there was no response to castration as opposed to slowed growth of LnCaP controls. These data indicate that the presence of the castration-induced ARv567es not only effects progression of prostate cancer by its own constitutive activity but also changes the function of the wt or full-length AR and provides an additional mechanism for AR-induced prostate cancer progression following castration. 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 631.
The new definition and diagnostic criteria of Parkinson's disease
Authors: Ronald B Postuma, Daniela Berg, Charles H Adler, Bastiaan R Bloem, Piu Chan, Günther Deuschl, Thomas Gasser, Christopher G Goetz, Glenda Halliday, Lawrence Joseph, Anthony E Lang, Inga Liepelt-Scarfone, Irene Litvan, Kenneth Marek, Wolfgang Oertel, C Warren Olanow, Werner Poewe, Matthew Stern
Journal: The Lancet Neurology (2016)
Toothpick impaction in the sigmoid colon as a cause of chronic abdominal pain
Authors: R. Grabysa, R. Łowczak, M. Kubiak, M. Kowalczyk, P. Zaborowski
Journal: Endoscopy (2010)

A 56-year-old male was admitted to our department with a 2-month history of recurrent lower abdominal pain accompanied periodically by fever. He had lost 7 kg in weight and had no history of melena or change in bowel habits or stool caliber.