tbuckley/cabot-search huggingface dataset:
Abstract 4255: Significance of mesenchymal stem cells in growth and metastasis of colon cancer
Authors: Kei Shinagawa, Yasuhiko Kitadai, Miwako Tanaka, Tomonori Sumida, Michiyo Kodama, Shinji Tanaka, Wataru Yasui, Kazuaki Chayama
Journal: Cancer Research (2010)

Abstract Background: Recently, mesenchymal stem cells (MSCs) are reported to migrate to tumor sites as well as sites of injury and to incorporate into tumor stroma, but the effects of interactions between MSCs and tumor cells and the mechanisms underlying these effects remain unclear. We examined the role of MSCs in the tumor micro-environment using an orthotopic colon cancer model and a model of liver metastasis from colon cancer. Materials and Methods: Human MSCs labeled with fluorescent dye were injected into tail veins of nude mice bearing KM12SM human colon cancer cells. KM12SM cells alone or KM12SM cells mixed with MSCs were transplanted into the cecal wall or spleen of nude mice. Differentiation of MSCs in primary colon tumors and metastatic liver tumors were also analyzed. Migration assay and invasion assay were performed to examine attraction between KM12SM cells and MSCs in vitro. Results: In in vivo experiments, systemically injected MSCs migrated to the stroma of orthotopic colon tumors and metastatic liver tumors. Orthotopic transplantation of KM12SM cells mixed with MSCs resulted in significantly greater tumor weight than did transplantation of KM12SM cells alone (p &amp;lt; 0.05). The survival rate was significantly lower in the mixed-cell group, and liver metastasis was seen only in this group (p &amp;lt; 0.001). Moreover, tumors resulting from transplantation of mixed cells had a significantly higher proliferating cell nuclear antigen labeling index (p &amp;lt; 0.01), significantly greater microvessel area (p &amp;lt; 0.01), and significantly lower apoptotic index (p &amp;lt; 0.001). Splenic injection of KM12SM cells mixed with MSCs resulted in a significantly greater number of liver metastases than did splenic injection of KM12SM cells alone (p &amp;lt; 0.01). MSCs incorporated into the stroma of primary and metastatic tumors expressed α-smooth muscle actin and platelet-derived growth factor receptor-β as carcinoma-associated fibroblast (CAF) markers. In in vitro experiments, KM12SM cells recruited MSCs, and MSCs stimulated migration and invasion of tumor cells through the release of soluble factors (p &amp;lt; 0.05, respectively). Conclusion: MSCs migrate and differentiate into CAFs in tumor stroma, and they promote growth and metastasis of colon cancer by enhancing angiogenesis and by inhibiting apoptosis of tumor cells. 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 4255.
RENTABILIDAD DE LA ULTRASONOGRAFÍA ENDOSCÓPICA (USE) EN PATOLOGÍA LITIÁSICA BILIOPANCREÁTICA
Authors: M Maraver Zamora, C Cano Medel, C Ortiz Moyano, P Guerrero Jiménez, M Romero Gómez
Journal: Endoscopy (2011)

Objetivos: 1 Definir rentabilidad de la USE como prueba diagnóstica en pacientes con patología biliopancreática sintomática litiásica según grupos de riesgo. 2. Establecer seguridad y valor predictivo respecto a otras herramientas diagnósticas.
Pathophysiology of Progressive Nephropathies
Authors: Giuseppe Remuzzi, Tullio Bertani
Journal: New England Journal of Medicine (1998)

In patients with renal diseases characterized by proteinuria, the initial insult to the kidney is usually followed by a progressive decline in the glomerular filtration rate. This decline has been thought to be due to changes in renal hemodynamics initiated by the loss of nephrons.1 When renal mass is reduced in rats, the remaining nephrons undergo sudden hypertrophy, with a concomitant lowering of arteriolar resistance and an increase in glomerular plasma flow.2,3 Afferent arteriolar tone decreases more than efferent arteriolar tone, and therefore, the hydraulic pressure in glomerular capillaries rises4 and the amount of filtrate formed by each nephron . . .
FRI0144 Adalimumab trough level in blood corresponding with clinical response
Authors: M.F. Pouw, C.L. Krieckaert, M.T. Nurmohamed, T. Rispens, L. Aarden, G. Wolbink
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Adalimumab is a recombinant human IgG1 monoclonal antibody with high specific binding to human tumor necrosis factor a (TNF). Since 2002 the drug has been approved for the treatment of rheumatoid arthritis (RA) and while several tests have been developed for testing drug levels and immunogenicity, the correlation between serum trough concentrations of this drug and therapeutic effect in clinical practice has not been studied yet. We propose that monitoring drug levels could make this treatment more cost-effective, specially considering the high costs of biologicals. <h3>Objectives</h3> To investigate the correlation between clinical improvement and serum trough concentrations of adalimumab in RA patients, 6 months after start of treatment. <h3>Methods</h3> Prospective cohort consisting of 201 patients treated with 40mg adalimumab every two weeks. Six months after start of treatment serum trough adalimumab levels were measured by ELISA. Clinical improvement was defined as the difference in Disease Activity Score 28 (DAS28) of the patients before start of the treatment, and after six months. Randomizing data as groups of ten patients gives a median trough and median Delta DAS28 (DDAS28). These findings were studied in a concentration-effect curve. <h3>Results</h3> After 6 months of treatment, serum trough concentrations varied between 0 to 33 ug/mL. Patients without detectable adalimumab did not respond clinically. All of these patients had developed anti-adalimumab antibodies. In patients with serum levels ranging from 3 to 12 ug/mL clinical response seemed to be related to serum adalimumab levels. Higher levels of adalimumab did not contribute further to clinical improvement. <h3>Conclusions</h3> This study indicates that serum trough levels of adalimumab fluctuate widely. To achieve clinical effect in RA, serum levels of 3 to 12 ug/mL could be sufficient. Hence, this suggests that presently a significant amount of patients is overtreated. Obviously, monitoring of drug levels is needed leading to personalized medication schemes allowing a more rational usage of this drug. <h3>Disclosure of Interest</h3> None Declared
LONG-TERM ASSOCIATION OF LDL CHOLESTEROL WITH CARDIOVASCULAR MORTALITY IN INDIVIDUALS AT LOW 10-YEAR RISK OF ATHEROSCLEROTIC CARDIOVASCULAR DISEASE: THE COOPER CENTER LONGITUDINAL STUDY
Authors: Shuaib Abdullah, Laura Defina, David Leonard, Carolyn Barlow, Nina Radford, Anand Rohatgi, Darren McGuire, James de Lemos, Jarett Berry, Amit Khera
Journal: Journal of the American College of Cardiology (2016)
AB0494 Systemic sclerosis and cancer risk: our experience
Authors: E. Lanciano, E. Praino, C. Rotondo, M. Covelli, F. Iannone, G. Lapadula
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> A higher incidence of cancer in Systemic Sclerosis (SSc) patients compared with the general population has been suggested by several observational studies reporting, however, different estimates. A recent meta-analysis has shown that, compared with the general population, the global relative risk (RR) to develop all invasive cancers in SSc patients was 1.75 (95% CI 1.41-2.18). Analysis of the single cancer sites indicated a strong association with lung cancer (RR 4.35; 95% CI 2.08-9.09), and a significant increased RR for hematologic neoplasms (RR 2.24; 95% CI 1.53- 3.29). The relation with breast cancer, previously reported by some epidemiological studies, was not confirmed (RR 1.05; 95% CI 0.86, 1.29). The aim of this study was to determine whether the incidence of cancer is increased among SSc patients in our center. <h3>Methods</h3> The study subjects consisted of 190 patients who had been consecutively evaluated between January 2008 until December 2012. We retrospectively reviewed their medical records and investigated the incidence rate of cancer. <h3>Results</h3> Eight out of 190 patients developed cancer (all females). The average age at diagnosis of cancer was 55,3 years. The types of cancers were: 3 Hodgkin Lymphoma (LnH), 1 Multiple Myeloma, 1 leukemya, 1 lung cancer, 1 colon cancer, 1 breast cancer. The overall rate of cancer in our SSc cohort was 3,7%, instead in Italian population is 4%. However, LnH rate was 37.5% of cancers, but its prevalence is 4-5% of cancer cases in general population. Therapy, autoantibodies, smoking, and lung involvement were not significantly different between SSc patients with or without cancer. <h3>Conclusions</h3> In our SSc patients, cancer prevalence was similar to that of Italian population. Hematologic cancers were more frequent than others. These data suggest that screening for cancer should be carried out in SSc like in general population, but that for blood cancer is strongly recommended in SSc, probably because of hyperactivation of the immune system. Further investigations are warranted to confirm these preliminary data and to understand the relationship between blood cancer risk and SSc. <h3>References</h3> Rheumatology (Oxford). 2013 Jan;52(1):143-54. doi: 10.1093/rheumatology/kes303. Epub 2012 Nov 22. Systemic sclerosis (scleroderma) and cancer risk: systematic review and meta-analysis of observational studies. Bonifazi M, Tramacere I, Pomponio G, Gabrielli B, Avvedimento EV, La Vecchia C, Negri E, Gabrielli A. Source Istituto di Clinica Medica, Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Via Tronto 10/A, 60100, Ancona, Italy. a.gabrielli@univpm.it. <h3>Disclosure of Interest</h3> None Declared
Tuning Reaction and Diffusion Mediated Degradation of Enzyme‐Sensitive Hydrogels
Authors: Stacey C. Skaalure, Umut Akalp, Franck J. Vernerey, Stephanie J. Bryant
Journal: Advanced Healthcare Materials (2016)

Enzyme-sensitive hydrogels are promising for cell encapsulation and tissue engineering, but result in complex spatiotemporal degradation behavior that is characteristic of reaction-diffusion mechanisms. An experimental and theoretical approach is presented to identify dimensionless quantities that serve as a design tool for engineering enzyme-sensitive hydrogels with controlled degradation patterns by tuning the initial hydrogel properties and enzyme kinetics. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Abstract 1470: 15-Deoxy-Δ12,14-prostaglandin J2 up-regulates expression of p53 and p21 through Nrf2-driven heme oxygenase-1 induction in human breast cancer (MCF-7) cells
Authors: Do-Hee Kim, Na-Young Song, Hye-Kyung Na, Eun-Hee Kim, Young-Joon Surh
Journal: Cancer Research (2010)

Abstract Heme oxygenase-1 (HO-1) is a stress-responsive enzyme that has antioxidant and cytoprotective functions. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), an endogenous ligand of peroxisome proliferator-activated receptor γ (PPARγ), has been reported to induce HO-1 and other antioxidant enzymes in certain cell lines. In the present work, we investigated the effects of HO-1 on the expression of p53 and p21 induced by 15d-PGJ2 in human breast cancer (MCF-7) cells. Treatment of MCF-7 cells with 15d-PGJ2 (30 μM) led to time-dependent increases in the expression of p53 and p21 as well as HO-1. The up-regulation of p53 and p21 expression by 15d-PGJ2 was abrogated by pharmacological inhibition with zinc protophophyrin (10 μM) or si-RNA knock down of HO-1. Nrf2, a basic-leucine zipper transcription factor, plays a key role in regulating the up-regulation of many antioxidant enzymes including HO-1. In MCF-7 cells transfected with NRF2 si-RNA, 15d-PGJ2 failed to induce expression of p53, p21 and HO-1. In addition, HO-1 inducers, such as cobalt protoporphyrin (25 μM) and hemin (10 μM), upregulated the expression of p53 and p21 without eliciting any apparent cytotoxicity. HO-1 degrades heme to produce iron, biliverdin, and carbon monoxide. We hypothesize that iron, a by-product of HO-1-catalyzed reactions, could mediate 15d-PGJ2-induced expression p53 and p21. Up-regulation of p53 and p21 expression by 15d-PGJ2 was abrogated by the iron chelator desferrioxamine (25 μM) in MCF-7 cells. Iron released from heme by HO-1 activity is mostly in the ferrous (Fe2+) form. When MCF-7 cells were treated with the iron-specific chelator phenanathroline (10 μM), 15d-PGJ2-induced expression of p53 and p21 was attenuated. However, p53 induction by 15d-PGJ2 was not affected by GW9662, a PPARγ antagonist. In addition, levels of the iron-sequestering protein H-ferritin were induced by 15d-PGJ2 in MCF-7 cells. Addition of the antioxidant N-acetylcysteine lowered the 15d-PGJ2-mediated H-ferritin levels. Recently, it has been reported that p21 as a positive regulator of Nrf2 extends the prosurvival function of p53 through recruitment of stress-response genes. Up-regulation of p53 and p21 expression via Nrf2-driven HO-1 induction and subsequent release of iron together with elevated expression of H-ferritin may confer resistance to oxidative damage in MCF-7 cells. 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 1470.
SUCCESSFUL CARDIAC TRANSPLANTATION OUTCOMES IN PATIENTS WITH ADULT CONGENITAL HEART DISEASE: A TEAM BASED APPROACH
Authors: Jonathan Menachem, Jessica Golbus, Maria Molina, Jeremy Mazurek, Edo Birati, Nicole Hornsby, Pavan Atluri, Stephanie Fuller, Yuli Kim, Lee Goldberg, Joyce Wald
Journal: Journal of the American College of Cardiology (2016)
Phase 2, Open-Label, International, Non-Comparative Study of MEDI4736 in Patients with Locally Advanced or Metastatic, Pd-L1 +, Stage 3B–4 Nsclc Who Have Received ≥2 Prior Systemic Treatment Regimens (ATLANTIC)
Authors: J.E. Gray, M.C. Garassino, J.F. Vansteenkiste, M. Ballas, D. Jayawardene, P.K. Stockman, J.D. Powderly, N. Rizvi
Journal: Annals of Oncology (2015)
P105 Outpatient survey of patient experience of hypertonic saline use in non-cystic fibrosis bronchiectasis
Authors: P Mitchelmore, C Sheldon, N Withers
Journal: Thorax (2013)

<h3>Introduction and Objectives</h3> Hypertonic Saline (HTS) is known to accelerate tracheobronchial clearance and is felt to provide a useful adjunct to physiotherapy for airway clearance in bronchiectasis<sup>1</sup>. Previous studies have demonstrated improvement in lung function, quality of life and healthcare utilisation with the use of HTS in non-CF bronchiectasis<sup>2</sup>. We have surveyed use and patient experience of HTS in our non-CF bronchiectasis clinic. <h3>Method</h3> All patients seen in our non-CF Bronchiectasis clinic over a four month period were invited to answer a questionnaire. Questionnaires were filled in anonymously and either returned to a box in clinic or by post. <h3>Results</h3> A total of 96 patients returned a questionnaire. Overall 114 patients were invited to respond, resulting in a response rate was 84%. 55 respondents (57%) were current or past users of HTS, with 36 (65%) of these still using HTS. 49 (89%) of those who had used HTS had done so for at least a month. The percentage of patients using HTS who indicated an improvement in Airway Clearance, Breathlessness and Quality of Life, were 80%, 60% and 67% respectively. Of the 19 patients who had stopped treatment, only 6 (32%) did so due to side effects. The total number of patients who had experienced side effects was 10 (18%). <h3>Conclusion</h3> Our survey demonstrates that a significant proportion of attendees to our non-CF Bronchiectasis clinic are taking, or have taken HTS treatment. Continued treatment is supported by positive feedback by patients on impact on symptoms and quality of life, as well as reasonable tolerability and side effect profile. <h3>References</h3> Kellett F, Redfern J, Niven RM. Evaluation of nebulised hypertonic saline (7%) as an adjunct to physiotherapy in patients with stable bronchiectasis. <i>Respir Med</i> 2005;99:27e31. Kellett F, Robert NM. Nebulised 7% hypertonic saline improves lung function and quality of life in bronchiectasis. <i>Respir Med</i>. 2011 Dec;105(12):1831–5
DIFFERENTIAL IMPACT OF RESIDUAL CORONARY LESIONS ON CLINICAL OUTCOMES AFTER PERCUTANEOUS CORONARY INTERVENTION BETWEEN PATIENTS WITH ACS AND NON-ACS IN LEFT MAIN CORONARY ARTERY
Authors: Tomohisa Tada, Koutarou Takahashi, Mamoru Toyofuku, Hirooki Higami, Yasushi Fuku, Hiroshi Muranishi, Kouji Nishida, Takeshi Morimoto, Takeshi Kimura, Hiroki Sakamoto
Journal: Journal of the American College of Cardiology (2016)
ACHIEVEMENT OF LIFESTYLE, BLOOD PRESSURE, LIPIDS AND DIABETES GOALS FOR PRIMARY PREVENTION OF CARDIOVASCULAR DISEASE ACROSS EUROPE: RESULTS OF EUROASPIRE IV SURVEY
Authors: Kornelia Kotseva, Dirk De Bacquer, Guy De Backer, Lars Ryden, Catriona Jennings, Viveca Gyberg, David Wood
Journal: Journal of the American College of Cardiology (2016)
Abstract SY02-01: Targeting the histone methyltransferase DOT1L in <i>MLL</i>-rearranged leukemia
Authors: Victoria M. Richon
Journal: Cancer Research (2012)

Abstract Protein methyltransferases (PMTs) are enzymes that catalyze the addition of methyl groups to the lysine and arginine residues of proteins, including histones. Recent evidence shows that PMTs are misregulated in a variety of cancers and thus may serve as therapeutic targets. A subset of acute leukemias have reciprocal translocations at 11q23 involving the PMT gene mixed lineage leukemia (MLL). MLL translocations occur in approximately 5% of adult acute lymphocytic leukemias (ALL) and 5 to 10% of adult acute myeloid leukemias (AML) including therapy-related leukemias. Multiple studies have demonstrated that patients with leukemias bearing the MLL translocation have a poor prognosis and are in need of new therapies. Translocations of the MLL gene result in the loss of the catalytic domain of the protein. The most common translocation partners, AF4, AF9 and ENL, recruit another PMT, DOT1L that methylates histone H3K79. Recruitment of DOT1L to the MLL fusion protein results in increased H3K79 methylation at MLL fusion protein target genes and elevated expression of the MLL target genes resulting in leukemogenesis. Mistargeted DOT1L enzymatic activity has therefore been proposed to be required for the development and maintenance of leukemias bearing the MLL translocation. To evaluate the potential of DOT1L as a therapeutic target in MLL- rearranged leukemia, we designed and characterized the DOT1L inhibitor EPZ004777, a small molecule with sub-nanomolar affinity for this enzyme and &amp;gt;1000 fold selectivity against other PMTs. EPZ004777 selectively inhibits intracellular histone H3K79 methylation in a concentration and time dependent manner. Significant changes in genes expression were observed in MLL-rearranged cell lines following the decrease in histone H3K79 methylation. Gene set enrichment analysis (GSEA) of genes downregulated following EPZ004777 treatment demonstrated strong enrichment for genes overexpressed in MLL-rearranged human acute leukemias as compared with MLL-germline acute leukemias. Phenotypically, EPZ004777 inhibits proliferation and induces apoptosis in human MLL-rearranged leukemia cell lines, with little effect on non-MLL-translocated cells. In vivo administration of EPZ004777 leads to extension of survival in a mouse MLL xenograft model. These studies provide compelling validation for the development of DOT1L inhibitors as targeted therapeutics for MLL-rearranged leukemia. 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 SY02-01. doi:1538-7445.AM2012-SY02-01
FRI0140 The clinical utility of CD64 expression on neutrophil in acute-onset interstitial lung damage complicated in patients with rheumatoid arthritis
Authors: Y. Arinuma, T. Matsui, A. Komiya, S. Nogi, K. Iwata, H. Futami, H. Takaoka, A. Hashimoto, H. Nakayama, S. Tohma
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Acute-onset interstitial lung damage (AILD) is one of the most cumbersome involvements complicated during the therapy for rheumatoid arthritis (RA). Especially, discrimination of the cause developing AILD is very important because that could have a great affect on choice of subsequent RA therapy. We have reported the up-regulation of CD64 molecule expression on neutrophil, which was a useful biomarker for detecting infection in patients with RA and can distinguish infection from RA flare, was also shown in interstitial lung damage (ILD) in RA. However, it is still unclear whether neutrophil CD64 could distinguish the cause of ILD. <h3>Objectives</h3> To assess the relationship between clinical causes developing AILD in patients with RA and the number of neutrophil CD64 molecule expression <h3>Methods</h3> Thirty-eight patients with RA who had admitted to our hospital due to AILD from 2005 to 2011 were enrolled in this study. Clinical diagnoses for AILD were retrospectively reviewed based on the medical records, laboratory data and the chest CT scan images. The number of neutrophill CD64 molecule expression before treatments of AILD were statistically compared among the groups classified according to the primary disease developing AILD. The cut-off of neutrophil CD64 was set at 2000 molecules/cell which had been reported to discriminate infection from a flare of arthritis in RA. <h3>Results</h3> Of 38 cases, 23 cases were classified into <i>Pneumocystis jiroveci</i> pneumonia (PCP) group, 8 cases were into methotrexate-induced pneumonia (MTX-IP) group and 7 cases were into extra-articular pulmonary involvement of RA (RA-IP) group. The number of CD64 molecule expression was 11077±7380 (mean ± SD) in PCP group, 4478±4834 in MTX-IP group and 5228±4507 in RA-IP group, respectively. The level of CD64 expression was significantly higher in PCP group compared with MTX-IP or RA-IP group, but there was no difference between MTX-IP and RA-IP group. The positive rate of CD64 expression (&gt;2000 molecules/cell) was 95.7% in PCP group, 50.0% in MTX-IP group and 85.7% in RA-IP group, respectively. <h3>Conclusions</h3> Our data indicates that neutrophil CD64 molecule expression up-regulates not only on infection but also on AILD in RA patients. However, the absolute elevation of neutrophil CD64 molecule expression level was different for respective cause developing AIDL. <h3>References</h3> Matsui T, et al. CD64 on neutrophils is a sensitive and specific marker for detection of infection in patients with rheumatoid arthritis. J Rheumatol. 2006 Dec;33(12):2416-24. <h3>Disclosure of Interest</h3> None Declared