tbuckley/cabot-search huggingface dataset:
Abstract 5517: MD-164 strongly inhibited various tumor cells and also metastasis of pancreatic tumor cells via modulation of Arp2/3 complexes.
Authors: Byoung-Mog Kwon, Young Min Han
Journal: Cancer Research (2013)

Abstract Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, University of Science and Technology in Korea Daejon 305-806, Republic of Korea The most difficult problem in the treatment of cancer patients is a metastatic recurrence. We focused to find novel anti-metastatic chemicals without cytotoxicity. In preliminary results, more than 800 commercially available pharmaceuticals and pre-clinical drugs were screened to identify inhibitors of tumor cell migration that are intimately tied to the steps of metastasis. The ARP2/3 complex which induces actin-polymerization and Y-branching is an essential element for lamellipodia, invadopodia and filopodia at the early stages of the metastasis in cells. Two classes of small molecule inhibitors of Arp2/3 were reported. However, inhibitors of ARPC1∼5 subunit have not yet been reported. Regulating the ARPC1∼5 subunits for inhibition of actin polymerization by utilizing small molecules will benefit actin based cell migration research. Furthermore, Inhibitors of specific ARPC1∼5 subunit are highly advantageous for developing anti-metastasis drug without toxicity and side effects. As a result of the screening, MD-164 was found to effectively reduce migration and invasion in various cancer cell lines by targeting an ARP2/3 complex subunit2, a component of actin related protein complex 2/3 (ARP 2/3). When AsPc-1 cells stably expressing luciferase were injected into the tail vein of the mice and the mice were treated with MD164, MD164 inhibited lung metastases about 70%. Citation Format: Byoung-Mog Kwon, Young Min Han. MD-164 strongly inhibited various tumor cells and also metastasis of pancreatic tumor cells via modulation of Arp2/3 complexes. [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 5517. doi:10.1158/1538-7445.AM2013-5517 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
A1.12 Endogenous SLPI released by rheumatoid synovial fibroblasts control BAFF-dependent-B cell activation in vitro and in the CIA and RA/SCID-arthritis models
Authors: N W Kam, F Brentano, D Kyburz, S Gay, A Filer, C Buckley, C Pitzalis, M Bombardieri
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Aims</h3> Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor with potent anti-microbicidal/immunoregulatory activities. Rheumatoid arthritis (RA) is characterised by synovial niches of autoreactive B cells. Autocrine production of B cell survival factor BAFF by RA synovial fibroblasts (RASF) supports ongoing B cell activation within the RA synovium. We investigated whether SLPI: (1)is produced by Toll-like receptors (TLRs)-treated RASF and regulates B cell activation; (2)exerts immunoregulatory effects in the RA synovium/SCID chimeric model and in collagen induced arthritis (CIA). <h3>Methods</h3> mRNA and protein expression of SLPI in RASF/RADF (dermal) stimulated with/without TLR2/TLR3/TLR4 ligands was assessed by QT-PCR and ELISA. RASF were treated with/without recombinant SLPI (rSLPI) to study: (1) BAFF expression; (2) AID expression and class-switching in co-culture with IgD+B cells. BAFF expression and antibody production were examined in rSLPI-treated RA/SCID mice. Severity of arthritis, anti-CII antibodies, and joint histopathology were studied in rSLPI-treated CIA mice. <h3>Results</h3> Stimulation of RASF with TLR3-ligands led to a 15-fold induction of SLPI mRNA. SLPI protein was time-dependently released from TLR3-stimulated RASF, but not RADF. SLPI restrained the production of BAFF, AID and IgA/G/M in TLR3-treated RASF and co-cultures, respectively. SLPI reduced BAFF expression and IgG/IgM production in RA/SCID mice while severity of arthritis, cartilage damage and anti-CII-IgG2a were reduced in SLPI-treated CIA. <h3>Conclusion</h3> RASF release high levels of SLPI constitutively and upon TLR3 stimulation. SLPI directly modulates BAFF and B cell activation in vitro/in vivo and reduces joint inflammation in CIA, highlighting a novel endogenous anti-inflammatory pathway with therapeutic potential in RA.
Brussels Meeting: Cancer's Controls Prove Complicated
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Brussels Meeting: Cancer's Controls Prove Complicated Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 11, 2 June 1993, Pages 856–858, https://doi.org/10.1093/jnci/85.11.856 Published: 02 June 1993
THE FIRST REPORT ON COMMUNICATING LEADLESS ANTI-TACHYCARDIA PACEMAKER AND SUBCUTANEOUS IMPLANTABLE DEFIBRILLATOR: THE NEXT STEP IN CARDIAC RHYTHM MANAGEMENT
Authors: Fleur Tjong, Tom Brouwer, Lonneke Smeding, Kirsten Kooiman, Allan Shuros, Brian Soltis, Brendan Koop, Arthur Wilde, Martin Burke, Reinoud Knops
Journal: Journal of the American College of Cardiology (2016)
SAT0013 Lupus Enteritis: Clinical Characteristics and Risk Factors Associated with Recurrence
Authors: B.S. Koo, Y.J. Kim, J.S. Oh, S. Hong, W.J. Seo, Y.-G. Kim, C.-K. Lee, B. Yoo
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Lupus enteritis is a severe complication of systemic lupus erythematosus (SLE) cases with acute abdominal pain. Some studies have identified clinical characteristics and risk factors for relapse in lupus enteritis <sup>1–4</sup>. However, no prognostic indicators of this disease have been described clearly to date. <h3>Objectives</h3> To compare the clinical characteristics of lupus enteritis and non-lupus enteritis patients with SLE and identify predictors of recurrence of lupus enteritis. <h3>Methods</h3> We retrospectively reviewed the medical records of 62 patients in our hospital who underwent an abdominal computer tomography (CT) scan between January 1997 and December 2013 for suspected lupus enteritis. CT scan findings including bowel wall edema, abdominal bowel-wall enhancement, and dilatation of the bowel lumen were used to confirm the diagnosis. We compared the clinical characteristics, laboratory data, and CT findings between lupus enteritis and non-lupus enteritis patients. <h3>Results</h3> Of our 62 SLE patients with enteric symptoms, the CT scan of 46 cases (68%) was compatible with lupus enteritis. The lupus enteritis cases showed a lower level of C4 than the non-lupus enteritis group (9.0±5.6 vs. 12.3±6.2, p=0.032). Recurrence of lupus enteritis was observed in 14 patients (28%) with a median number of 2.5 episodes (range, 1-8). Recurrent cases showed more colon (78% vs. 40%, p=0.026) and urinary tract (57% vs. 25%, p=0.048) involvement than the non-recurrent group. The hemoglobin and albumin levels were significantly higher in recurrent patients (p=0.013, p=0.023). The adjusted hazard ratio (HR) of variables associated with recurrence were 4.689 for colon involvement (95% confidence interval (CI): 1.245-17.659, p=0.0220, 5.468 for urinary tract involvement was (95% CI: 1.629-18.360, p=0.006), and 1.329 for hemoglobin (95% CI: 1.034-1.707, p=0.026). <h3>Conclusions</h3> A low C4 is helpful in diagnosing lupus enteritis. Colon and urinary tract involvement is associated with the recurrence of lupus enteritis. <h3>References</h3> Janssens P, Arnaud L, Galicier L, et al. Lupus enteritis: from clinical findings to therapeutic management. Orphanet J Rare Dis 2013;8:67. Kim YG, Ha HK, Nah SS, et al. Acute abdominal pain in systemic lupus erythematosus: factors contributing to recurrence of lupus enteritis. Ann Rheum Dis 2006;65:1537-8. Kwok SK, Seo SH, Ju JH, et al. Lupus enteritis: clinical characteristics, risk factor for relapse and association with anti-endothelial cell antibody. Lupus 2007;16:803-9. Yuan S, Ye Y, Chen D, et al. Lupus mesenteric vasculitis: Clinical features and associated factors for the recurrence and prognosis of disease. Semin Arthritis Rheum 2013. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2797
Abstract 3364: Upregulation of sonic hedgehog contributes to TGF-β1-induced epithelial to mesenchymal transition in NSCLC cells
Authors: Ma'in Y. Maitah, Shadan Ali, Aamir Ahmad, Shirish Gadgeel, Fazlul H. Sarkar
Journal: Cancer Research (2011)

Abstract Background: Lung cancer especially non-small cell lung cancer (NSCLC) is the major cause of cancer-related deaths in the United States, and the aggressiveness of NSCLC has been shown to be associated with the acquisition of epithelial-to-mesenchymal transition (EMT). The acquisition of EMT phenotype induced by TGF-β1 in several cancer cells has been implicated with tumor aggressiveness and resistance to conventional therapeutics; however, the molecular mechanism of EMT and tumor aggressiveness in NSCLC remains unknown. Methodology/Principal Findings: In this study, we found, for the first time, that the induction of EMT by chronic exposure of A549 NSCLC cells to TGF-β1 (A549-M cells) led to the up-regulation of sonic hedgehog (Shh) both at the mRNA and protein levels causing activation of hedgehog signaling. Induction of EMT was found to be consistent with aggressive characteristics such as increased clonogenic growth, cell motility and invasion. The aggressiveness of these cells was attenuated by treatment of A549-M cells with pharmacological inhibitors of Hh signaling in addition to Shh knock-down by siRNA. The inhibition of Hh signaling by pharmacological inhibitors led to the reversal of EMT phenotype as confirmed by the reduction of mesenchymal markers such as ZEB1 and Fibronectin, and induction of epithelial marker E-cadherin. Conclusions/Significance: These results suggest that transcriptional up-regulation of Shh signaling is mechanistically associated with TGF-β1 induced EMT phenotype, and thus the inhibitors of Shh signaling could be useful for the reversal of EMT phenotype, which would inhibit the metastatic potential of NSCLC cells and also make these tumors more sensitive to conventional therapeutics. 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 3364. doi:10.1158/1538-7445.AM2011-3364
Added Value of Attenuation-Corrected Myocardial Perfusion Scintigraphy in a Patient with Dextrocardia
Authors: RIEMER H. J. A. SLART, JAEP DE BOER, PIETER L. JAGER, D. ALBERT PIERS
Journal: Clinical Nuclear Medicine (2002)

J. A. SLART, RIEMER H. M.D.; DE BOER, JAEP M.D., Ph.D.; JAGER, PIETER L. M.D., Ph.D.; PIERS, D. ALBERT M.D., Ph.D. Author Information
P253 ENDOPLASMIC RETICULUM STRESS DOES NOT CONTRIBUTE TO NASH PATHOGENESIS IN OBESE, DIABETIC MICE WITH METABOLIC SYNDROME
Authors: V. Legry, D.M. Van Rooyen, B.A. Lambert, C. Sempoux, L. Poekes, R. Español-Suñer, Y. Horsmans, G.C. Farrell, I.A. Leclercq
Journal: Journal of Hepatology (2014)
CLINICAL UTILITY OF AUTOMATIC QUANTITATIVE CORONARY ARTERY STENOSIS ANALYSIS ON CORONARY COMPUTED TOMOGRAPHY ANGIOGRAPHY: COMPARISON WITH INTRAVASCULAR ULTRASOUND
Authors: Hyung Bok Park, Ran Heo, Hyuk-Jae Chang, Reza Arsanjani, Sanghoon Shin, Sung Gyun Ahn, Byoung Kwon Lee, Myeong-Ki Hong, Yangsoo Jang, Namsik Chung
Journal: Journal of the American College of Cardiology (2015)
On the evolution and growth of lateralization
Authors: Michael C. Corballis
Journal: Behavioral and Brain Sciences (1981)

This is a welcome attempt to seek common biological principles underlying laterality in animals and humans. I do not think it is wholly convincing, but this is partly because many of the results from nonhuman species are not yet firmly established or understood. I suspect that the author's characterization of lateralization, with the left hemisphere supposedly specialized for communicative functions and the right for spatial and affective functions, will require modification. For instance, it now seems fairly clear that the left hemisphere in humans plays a general role in the production and perception of sequences not restricted to communicative acts (Craig 1980; Kimura 1979), and indeed some of the examples of left-hemispheric specialization listed in Table 2 are not obviously communicative. Even so, there are some fairly striking parallels between humans and nonhumans with respect to the pattern of lateralization, and one suspects that common principles are operating. At the same time, in the enthusiastic search for functional asymmetries, we should not overlook the striking degree of bilateral symmetry that characterizes the brains of all animals, including humans.
MODERATELY ELEVATED MITRAL MEAN GRADIENT AFTER PERCUTANEOUS EDGE-TO-EDGE REPAIR OF MITRAL REGURGITATION IS NOT ASSOCIATED WITH EXACERBATION OF HEART FAILURE
Authors: Richard Cheng, Emily Tat, Robert Siegel, Reza Arsanjani, Asma Hussaini, Alfredo Trento, Saibal Kar
Journal: Journal of the American College of Cardiology (2016)
VASOPEPTIDASE INHIBITION IMPROVES SURVIVAL IN PATIENTS WITH HEART FAILURE: META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Authors: Bhavi Pandya, Achint Patel, Shreya Pandya, Armaghan Soomro, Jonathan Spagnola, Sainath Gaddam, Ruben Kandov, James Lafferty
Journal: Journal of the American College of Cardiology (2016)
OUTCOMES IN PATIENTS UNDERGOING CORONARY ARTERY BYPASS GRAFTING BASED ON HOSPITAL VOLUME, 2007-2011
Authors: Jake Chanin, Dmitriy Feldman, Rajesh Swaminathan, Robert Minutello, Jason Jones, Shirley Xu, Geoffrey Bergman, Ryan Kaple, Bobby Ghosh, Subhi Alaref, Harsimran Singh, Shing-Chiu Wong, Luke Kim
Journal: Journal of the American College of Cardiology (2015)
THE TREATMENT-RESISTANT MESENCHYMAL SIGNATURE IN GLIOBLASTOMA DERIVES FROM TUMOR CELLS INDEPENDENT OF STROMA
Authors: E. P. Sulman, Q. Wang, R. Ezhilarasan, L. D. Goodman, J. Gumen, P. Sun, K. Aldape, W. Alfred Yung, T. Heffernan, G. F. Draetta, F. F. Lang
Journal: Neuro-Oncology (2014)

BACKGROUND: Glioma sphere-forming cells (GSCs) derived from surgical specimens are a fundamental resource to study glioblastoma (GBM) biology. Mesenchymal-expressing GSCs have been proposed as a source of treatment resistance and mesenchymal tumors correlate with poorer survival. Recently, we found that the anti-angiogensis drug bevacizumab appeared to provide no benefit to patients with mesenchymal tumors, in contradiction to expectations that a mesenchymal microenvironment may benefit from anti-angiogenesis therapy. We have developed a collection of GSCs that have undergone comprehensive genomic characterization, similar to that performed by the Cancer Genome Atlas (TCGA) for whole tumor specimens. We hypothesized that the genomic landscape of GSCs would recapitulate what was observed by TCGA. METHODS: 47 GSCs were obtained from primary culture of fresh tumor specimens obtained at surgery and cultured as 3-dimensional spheres in the absence of serum. All lines were subjected to RNAseq (75bp paired-end, 100X coverage), copy number analysis (Affymetrix Oncoscan 2.0), whole methylome (Illumina Infinium 450k bead array), and targeted resequencing of known cancer-associated genes. Whole exome sequencing was performed for 22 GSCs. Gene expression was determined by reads per kilobase per million (RPKM) using an RNA sequencing data analysis pipeline (PRADA) and somatic mutations identified by a commonly used detection method (MuTech). Consensus clustering based on none-negative matrix factorization (CNMF) was performed on expression data and correlation to TCGA clusters determined by single-sample gene set enrichment analysis (ssGSEA). RESULTS: While global copy number alterations such as gain of chromosome 7 at the EGFR locus or loss of chromosome 10 at the PTEN locus were shared between tumor and matched GSC, the rate of somatic events was significantly higher in GSCs compared to tumors (range 47-570, median 124 vs range 2-255, median 65). Optimization of CNMF identified a total of 5 gene-expression clusters. GSCs in only one of these clusters showed enrichment for a unique TCGA class, mesenchymal. GSCs in other clusters were divided among multiple TCGA classes. CONCLUSIONS: Mesenchymal glioblastomas are derived from mesenchymal GSCs, suggesting that the tumor component is the largest contributor to the aggressive biology of this subtype. GSCs from other tumor subtypes correlate to multiple TCGA classes, suggesting that tumor stroma may contribute to the expression phenotype in those cases. Therapeutics targeting the microenvironment, such as anti-angiogenesis drugs, may have a greater role in non-mesenchymal tumors where the stromal contribution is more prominent. SECONDARY CATEGORY: Neuropathology & Tumor Biomarkers.
Abstract P4-03-10: Sonographic-pathological correlation in contrast-enhanced ultrasonography in the diagnosis of breast cancers.
Authors: K Kato, Y Miyamoto, M Kamio, H Nogi, Y Imawari, R Mimoto, Y Toriumi, N Nakata, H Takeyama, K Uchida
Journal: Cancer Research (2012)

Abstract Background: As contrast-enhanced ultrasonography (CEUS) in the diagnosis of breast masses has been performed less frequently than other imaging modalities, it's efficacy evaluation has not been established. CEUS with Sonazoid, which is microbubble-based contrast agent, allows visualization of the mass bloodstream, therefore the classification of enhancement patterns in CEUS could increase diagnostic yield for breast masses. To achieve this, a clear standard for the CEUS evaluation is needed. The purpose of this study was to identify CEUS findings for malignancies and clarify sonographic-pathological correlation of breast cancers. Material and Method: Present study included 20 patients with invasive ductal cancer who underwent operation for primary therapy without any chemotherapy or hormonal therapy. We contrasted CEUS features with Sonazoid with surgical specimens retrospectively. As malignant findings, the presence of focal perfusion defects inside masses and enhancement of outside masses were chosen. Result: All of the 20 cases displayed focal perfusion defects. 9 cases of those could be successfully assessed in the same sections histopathologically and ultrasonographically. Histopathological findings showed those defects to be fibrotic foci inside masses in 7cases (77.7%). While, 6 cases of all (30%) showed stains outside tumor, and only one case was found out to be fibrotic growth with cancer cells. Conclusion: focal perfusion defects of breast masses in CEUS were considered to be specific for malignancy, and they seemed to be fibrotic foci histopathologically. Desmoplastic reaction has been observed in epithelial solid tumor biology, and if those defects reflect the desmoplasia defects could be the proof of malignancy. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-03-10.
AB1111 Disability in adult patients with idiopathic juvenile arthritis
Authors: A.-M.-M. Ramazan, M. Suta
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Juvenile Idiopathic Arthritis (JIA) is a inflammatory rheumatic disease of childhood that is reported with prevalence with large limits between 7 and 400/100 000 children. Although only a minority of patients with JIA have inflammatory disease as adult, functional involvement is significant. The prognosis was evaluated in many clinical trials through remission rate, functionality and radiological destruction on different groups, especially in children. <h3>Objectives</h3> To assess disability in patients with persistent disease in a cohort of adult with JIA comparative with a group with rheumatoid arthritis from our district seen between May 2010 and Apr 2011. <h3>Methods</h3> 21 patients with juvenile idiopathic arthritis, using ILAR criteria, were assessed. We had excluded the patients with juvenile ankylosing spondylitis. The outcome assessment included demographic, clinical status (disease activity, disability with HAQ score, damage assessment with JADI score), quality of life(SF-36) and inflammation tests (ESR,CRP). The control group with rheumatoid arthritis (26 patients) from our department were assessed on the same manner. The functional outcome were determined with linear regression. <h3>Results</h3> The study patients had moderate disability with a mean of HAQ score 1.31±0.93 (95% CI=0.93-1.69). Through ANOVA test the results are similar with the group with rheumatoid arthritis (1.25±0.70). However we have noticed that 19% of study patients are no disability (p=0.06) in contrast with control patients. The HAQ score is influenced by pain (VAS, patient global assessment, tender joints), joint damage and by active disease. Therefore, the quality of life is decreased proportionally depending on disability and disease duration in contrast with control patient. <h3>Conclusions</h3> Disability of adult patients with JIA after 21 years is moderate, but it is increasing proportionally with time and is most influencing by clinical factors. <h3>Disclosure of Interest</h3> None Declared
Abstract 2646: N-ethylmaleimide modulates gemcitabine effect on ribonucleotide reductase M1 subunit (RRM1)
Authors: Zhengming Chen, Gerold Bepler
Journal: Cancer Research (2011)

Abstract Ribonucleotide Reductase M1 (RRM1) is the regulatory subunit of the holoenzyme that catalyzes the conversion of ribonucleotides (NTP) to 2’-deoxyribonucleotides (dNTP) in mammalian cells. Its function is indispensible in cell proliferation and DNA repair. It is also a crucial marker of therapeutic efficacy in various cancers. This study investigated how the alkylating agent N-ethylmaleimide (NEM) interacts with the antimetabolite gemcitabine in inhibiting its target protein RRM1. Lung cancer cell lines and the human embryonic kidney cell line (HEK293) were used for transfection, immunoprecipitation, and proliferation assays. Site-directed mutagenesis was used to create point mutations. The protein ID and modification sites were identified by LC/MS/MS. Flow cytometry was used for sorting and plating cells. Mouse xenografts were used for in vivo validation. When cells were treated with gemcitabine and the alkylating agent NEM, a novel 110kD band, along with the 90kD native RRM1 band, was recognized in immunoblots. This 110kD band was identified as RRM1 by LC/MS/MS. It is specific to gemcitabine/NEM, among 11 chemotherapy drugs and 3 alkylators tested. It can also be detected in the mouse xenografts treated with gemcitabine. We mutated 7 residues that are essential for the RRM1 activity to alanine. Among these mutants, C218A, C429A, and E431A did not show any 110kD band, while C444A, N427A, C787A and C790A showed diminished 110kD, suggesting the 110kD RRM1 is involved in functionality. This was further confirmed by proliferation assays with gemcitabine and NEM in wild type and mutant cells. In conclusion, the alkylator NEM specifically modulates the gemcitabine-RRM1 interaction and understanding the mechanism may lead to improved efficacy of and reduced resistance to gemcitabine. 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 2646. doi:10.1158/1538-7445.AM2011-2646