tbuckley/cabot-search huggingface dataset:
Abstract 4842: Lysosomal-associated protein multispanning transmembrane 5 gene (LAPTM5) is associated with spontaneous regression of neuroblastomas
Authors: Jun Inoue, Akiko Misawa, Yukichi Tanaka, Shizuko Ichinose, Yuriko Sugino, Hajime Hosoi, Tohru Sugimoto, Issei Imoto, Johji Inazawa
Journal: Cancer Research (2010)

Abstract Background; Neuroblastoma (NB) is the most frequently occurring solid tumor in children, and shows heterogeneous clinical behavior. Favorable tumors, which are usually detected by mass screening based on increased levels of catecholamines in urine, regress spontaneously via programmed cell death (PCD) or mature through differentiation into benign ganglioneuroma (GN). In contrast, advanced-type NB tumors often grow aggressively, despite intensive chemotherapy. Understanding the molecular mechanisms of PCD during spontaneous regression in favorable NB tumors, as well as identifying genes with a pro-death role, is a matter of urgency for developing novel approaches to the treatment of advanced-type NB tumors. Key findings; We found that the expression of lysosomal associated protein multispanning transmembrane 5 (LAPTM5) was usually down-regulated due to DNA methylation in an NB cell-specific manner, but up-regulated in degenerating NB cells within locally regressing areas of favorable tumors detected by mass-screening. Experiments in vitro showed that not only a restoration of its expression but also the accumulation of LAPTM5 protein, was required to induce non-apoptotic cell death with autophagic vacuoles and lysosomal destabilization with lysosomal-membrane permeabilization (LMP) in a caspase-independent manner. While autophagy is a membrane-trafficking pathway to degrade the proteins in lysosomes, the LAPTM5-mediated lysosomal destabilization with LMP leads to an interruption of autophagic flux, resulting in the accumulation of immature autophagic vacuoles, p62/SQSTM1, and ubiqitinated proteins as substrates of autophagic degradation. In addition, ubiquitin-positive inclusion bodies appeared in degenerating NB cells. Conclusions; We propose a novel molecular mechanism for PCD with the accumulation of autophagic vacuoles due to LAPTM5-mediated lysosomal destabilization. LAPTM5-induced cell death is lysosomal cell death with impaired autophagy, not cell death by autophagy, so-called autophagic cell death. Thus LAPTM5-mediated PCD is closely associated with the spontaneous regression of NBs and opens new avenues for exploring innovative clinical interventions for this tumor. 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 4842.
AB0177 Toll-Like Receptors - Differences between Healthy Control, ANCA Associated Vasculitis and Lupus Kindeys - Preliminary Pilot Study
Authors: H. Ciferska, V. Tesar, E. Honsova, A. Lodererova, Z. Hruskova, K. Pavelka
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is characterized by a defective monocyte/macrophage-mediated clearance of the apoptotic (nucleic acid-containing) particles in vitro. The large amount of nucleic acids, free and/or complexed, are present in circulation and/or locally released. They can be entrapped in kidney from the blood stream.On the other hand bacterial infections are associated with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). Our hypothesis is that those nucleic acids are bound by renal Toll-like receptors (TLR). TLRs participate in innate immune response through their ability to recognize and bind to various microbial structures. This might lead to cross-reactions with endogenous nucleic acids, which can escape clearence of apoptotic rests, leading to renal injury. <h3>Objectives</h3> Our objective was to assess and compare expresion of TLR-7,-8 and -9 in healthy controls, ANCA associated vascuitis and lupus kidneys. <h3>Methods</h3> The residual paraffin embedded kidney biopsy samples were used for this study. There were 8 samples with lupus nephritis (LN) (6 females and 2 males) (class II 2 patients, class III 6 patients), 5 samples with AVV with renal involvement and 3 controls without glomerular disease (wedge biopsies obtained during transplantation surgery). The following antibodies were used for the immunohistochemistry: anti-TLR-7 (LSBio,Seattle, WA) and anti -TLR-8 and -9 (Sigma-Aldrich,St.Louis, MO). <h3>Results</h3> Normal kidney contained some single-stranded RNA binding (TLR-8) receptors but in particular double-stranded RNA binding receptor TLR-7 mostly in distal tubuli and minimal expersion of DNA binding TLR-9 was found. SLE kidneys contained more TLR-7, TLR-8 and TLR-9 then healthy controls, however the stronger expression of TLR-8 and -9 was found in tubuli of patients with AAV. <h3>Conclusions</h3> It is concluded that kidneys have a capacity to bind nucleic acids and that this ability is altered in different types of glomerulonephritides in SLE and AAV. TLR stimulation leads to the production of tumor necrosis factor-α and of other pro-inflammatory cytokines and to up-regulation of co-stimulatory molecules necessary for the adaptive immune response, which is possibly directed against endogenous nucleic acids. <h3>Acknowledgements</h3> Supported by the project (Ministry of Health, Czech Republic) for conceptual development of research organization 00023728 (Institute of Rheumatology) <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3235
P983 VALIDATION OF THE HEPATOME ARTERIAL-EMBOLIZATION PROGNOSTIC (HAP)-SCORE IN AN AUSTRIAN TACE COHORT
Authors: M. Pinter, F. Hucke, I. Graziadei, W. Vogel, M. Trauner, W. Sieghart, M. Peck-Radosavljevic
Journal: Journal of Hepatology (2014)
THU0479 Dheas-Associated Genotypes Contribute to Adrenal Androgen Hypofunction in RA
Authors: L. Chovanova, M. Mravcova, R. Imrich, J. Rovensky, L. Paulikova, M. Rakicka, A. Marko, A. Penesova, H. Radner, G. Steiner, J. Smolen, M. Vlcek
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Lower levels of dehydroepiandrosterone sulphate (DHEAS) were found in chronic inflammatory diseases such as rheumatoid arthritis (RA), however, mechanisms for this decrease remains unclear. Recently, several genes has been found to be associated with lower DHEAS levels [1]. <h3>Objectives</h3> The aim of our study was to analyze frequency of selected single nucleotide polymorphisms (SNPs) known to be associated with low DHEAS in RA patients and their impact on DHEAS levels during disease. <h3>Methods</h3> 1034 participants (438 RA, 596 controls) were analyzed for SNPs in genes ZKSCAN5 (rs11761528), SULT2A1 (rs2637125), HHEX (rs2497306) and ARPC1A (rs740160) by real-time PCR genotyping assay. Serum DHEAS concentration was measured in 156 RA patients and 102 healthy controls by ELISA. <h3>Results</h3> RA patients had significantly lower DHEAS than controls (age-adjusted), in female (p&lt;0.001) as well as in male subgroup (p=0.013). The frequency of DHEAS-related SNPs were similar in RA and control groups. In RA female patients linear regression model adjusted for age and glucocorticoid treatment, showed significant effect of risk alleles in SULT2A1 (p&lt;0.05) and HHEX (p&lt;0.05) genes to lowering serum DHEAS levels. <h3>Conclusions</h3> Complex interactions exist between DHEAS-associated genotypes and adrenal androgen hypofunction in RA suggesting a significant contribution to adrenal androgen hypofunction in RA. <h3>References</h3> Zhai G et al. Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms. PLoS Genet. 2011; 7(4):e1002025. <h3>Acknowledgements</h3> Study was supported by VEGA 2/0018/12 <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5779
OP0066 Efficacy of rituximab in systemic manifestations of patients with primary sjÖgren’s syndrome: Results from the air registry
Authors: G. Cinquetti, C. Larroche, B. Combe, E. Hachulla, O. Meyer, E. Pertuiset, G. Kaplanski, X. Mariette, J.-E. Gottenberg
Journal: Annals of the Rheumatic Diseases (2012)

Gustatory stimuli, such as sugar, induce a behavioral response in<i>Drosophila</i> that involves extension of the proboscis and consumption of the sugar-containing solution. Addition of salt to the sugar solution inhibits this behavioral response. However, the mechanisms and gene products involved in the salt aversion response have not been described. Here, we report the identification of a locus, defective proboscis extension response (<i>dpr</i>), that is required for salt aversion. <i>dpr</i> was expressed in a subset of primary neurons in the gustatory organs and encoded a protein with two Ig-like domains, a single putative transmembrane domain, and a short region C terminal to the transmembrane segment. In addition, DPR defines a large previously unknown group of ≥20 highly related Ig-containing proteins.
CHARACTERIZATION AND IMPACT OF COMORBIDITY AMONG GENDER AND RACIAL SUBGROUPS HOSPITALIZED WITH HEART FAILURE WITH PRESERVED EJECTION FRACTION
Authors: Parag Goyal, Tracy Paul, Zaid I. Almarzooq, Rajesh Swaminathan, Dmitriy Feldman, Janey Peterson, Maria Karas, Irina Sobol, Evelyn Horn, Luke Kim
Journal: Journal of the American College of Cardiology (2016)
Abstract P6-08-03: MYC Amplification and Overexpression Discriminate Secondary from Primary Angiosarcoma of the Breast
Authors: NS Hadj-Hamou, YM Kirova, M Laé, X Sastre-Garau, B. Malfoy
Journal: Cancer Research (2010)

Abstract Background: Secondary angiosarcoma of the breast is defined as a sarcoma developed in the irradiated field in patients previously treated for breast carcinoma. These tumors represent 25% to 50% of sarcomas developed after irradiation for breast cancer and are of poor outcome. Up to now, there are no criteria to distinguish primary from secondary angiosarcomas. The aim of this work was to identify molecular features able to discriminate these two types of tumors. Material and Methods: Our study was mainly based on the use of whole genome (SNP array) and whole transcriptome (mRNA and miRNA microarray) approaches. Others methods included quantitative PCR, reverse transcription quantitative PCR, fluorescence in situ hybridization and immunohistochemistry. All patients’ records were reviewed and the clinical information about the primary and secondary sarcomas was recorded. For all radiation-induced sarcomas, the patients’ radiotherapy plans were reviewed and it was confirmed that the tumors respected the classic Cahan's criteria to confirm their secondary nature. Results: Amplification (5 to 50 fold) of the MYC oncogene was found in all breast secondary angiosarcomas (19 cases) but in none of primary angiosarcomas (6 cases) (p-value = 2.353e-05). MYC amplification was associated with mRNA and protein overexpression of this gene. In tumors with a MYC amplification, numerous genes corresponding to MYC targets and coding for mRNA or miRNAs were found to be deregulated as compared with expression levels observed in tumors without amplifications. These data point to the pathways preferentially involved in the pathogenesis of secondary angiosarcomas of the breast. The relationships between clinical, pathological and biological features are studied. Conclusions: MYC is amplified and overexpressed in secondary angiosarcomas of the breast. We suggest to exploit these characteristic features as a diagnostic criteria to distinguish primary from secondary angiosarcomas of the breast. Furthermore, those newly identified characteristics of secondary angiosarcomas could serve as a basis for tailored therapeutic approaches. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-08-03.
¿ES UTIL UN METODO DE TRACCION (CLIP-BANDA) PARA FACILITAR LA DISECCION SUBMUCOSA GASTRICA?. ESTUDIO PROSPECTIVO, ALEATORIZADO, CONTROLADO, EN MODELO PORCINO IN VIVO
Authors: A Parra Blanco, T Uraoka, J Ortiz Fernández-Sordo, S Fernández García, H Alonso, P Amor, A Jiménez, MT Sánchez Alvarez, A Brea Pastor, L Rodrigo
Journal: Endoscopy (2011)

Introducción: El método del clip-banda para la Disección Endoscópica Submucosa (DES) ha demostrado previamente su aplicabilidad en un modelo porcino vivo y en humanos. Sin embargo este método no se ha comparado con la técnica convencional de DES.
THE RATIO OF TRANSMITRAL E-WAVE VELOCITY TO LEFT ATRIAL STRAIN AND LEFT ATRIAL STRAIN ITSELF CAN RESPECTIVELY PREDICT CARDIOVASCULAR AND SUBSEQUENT STROKE OUTCOMES IN PATIENTS WITH ATRIAL FIBRILLATION
Authors: Ho-Ming Su, Feng-Hsien Lin, Po-Chao Hsu, Wen-Chol Voon, Wen-Ter Lai, Sheng-Hsiung Sheu
Journal: Journal of the American College of Cardiology (2015)
NURSING/ALLIED HEALTH
Authors: A. Kumar, V. Chinnabhandar, A. Gupta, A. K. Gupta, N. Radhakrishnan, S. P. Yadav, A. Sachdeva, J. Sastry, M. Ronghe, D. Murphy, A. Hall, J. Belmore, K. Marshall, A. Clarkin, C. Castor, C. Kaise, S. Bognar, N. Law, E. Bouffet, D. Mabbott, M. S. Hemenway, N. K. Foreman, J. R. Madden, J. R. Madden, M. S. Hemenway, N. K. Foreman, S. Z. Rush, M. Hemenway, N. Foreman, T. Dinkel
Journal: Neuro-Oncology (2014)
Case 37-2015
Authors: Josalyn L. Cho, Shaunagh McDermott, Athe M. Tsibris, Eugene J. Mark
Journal: New England Journal of Medicine (2015)

A 76-year-old man with a history of transitional-cell carcinoma of the bladder presented with persistent fever, leukopenia, and pulmonary infiltrates. Examination of a lung-biopsy specimen revealed noncaseating granulomatous inflammation. A diagnostic test was performed.
Radioactive Defect on I-123 MIBG Myocardial SPECT Imaging in a Patient with Cardiac Sarcoidosis
Authors: ERIKA IMAI, TATSURO KAMINAGA, KOUICHI TAKADA, KIMIKO KUTOMI, SHIGERU FURUI
Journal: Clinical Nuclear Medicine (2002)

IMAI, ERIKA M.D.; KAMINAGA, TATSURO M.D.; TAKADA, KOUICHI M.D.; KUTOMI, KIMIKO M.D.; FURUI, SHIGERU M.D. Author Information
Abstract B54: The ability of NK cells to perform missing-self rejection of target cells is quantitatively different between individuals and controlled by MHC class I through a process of education
Authors: Petter Brodin, Klas Kärre, Petter Höglund
Journal: Cancer Research (2011)

Abstract NK cells have the capacity to efficiently kill tumor cells. NK cells will be triggered to do so upon loss of MHC class I expression on the tumor cells, that is missing-self recognition. However, not all NK cells in an individual are able to perform such missing-self responses. The ability to perform missing-self is acquired through a process of education where only NK cells with an ability to interact with MHC class I are allowed full functionality. We have recently shown that this NK cell education is not a binary but a quantitative process, yielding NK cells that are more or less efficient killers depending on the strength of interaction with self MHC class I during education (Brodin et al Blood 2009). Here we describe our latest unpublished results on the MHC class I medicated influence on the NK cell system in the mouse. We show that MHC class I not only controls function but also NK cell population dynamics leading to a repertoire of NK cells that differ between individuals in a MHC class I dependent way. Combined these MHC class I mediated effects control the ability of an individual to perform missing-self responses cells lacking MHC class I in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr B54.
Abstract 2760: Phase I study of MK-0646, the humanized monoclonal antibody against IGF-1R in combination with gemcitabine or gemcitabine + erlotinib (E) for advanced, previously untreated pancreatic cancer
Authors: Rachna T. Shroff, Gauri R. Varadhachary, Priya Bhosale, Lerma Ukegbu, Michael J. Overman, Robert A. Wolff, James L. Abbruzzese, Milind M. Javle
Journal: Cancer Research (2010)

Abstract BACKGROUND: MK-0646 binds to IGF-1R and blocks its interaction with the IGF-I/ II ligands, enhances gemcitabine (G)-induced apoptosis and inhibits the MEK/ Erk and the PI3-kinase/ Akt signaling pathways which are important in cellular proliferation, survival and drug resistance in pancreatic cancer. Receptor cross-talk between IGF-1R and EGFR and enhanced IGF-1R-induced activation of the PI3-kinase/ Akt pathways mediate resistance to anti-EGFR agents such as E. The combination of IGF-1R and EGFR antagonists has demonstrated synergy in preclinical pancreatic cancer models. METHODS: Patients with stage IV, previously untreated pancreatic cancer, ECOG performance status (PS) 0-1, adequate hematologic and organ function were enrolled. MK-0646 was escalated in two dose levels using 3+3 statistical design. Uncontrolled hyperglycemia or cardio-respiratory conditions were exclusions. Blood was collected at study entry for IGF-1 and IGFBP-3 levels. Arm A: G 1000 mg/m2 over 100 min, weekly x 3, MK-0646 over 60 min: 5 or 10 mg/kg, weekly x 4; Arm B: G 1000 mg/m2 over 100 min, weekly x 3, MK-0646 over 60 min: 5 or 10 mg/kg, weekly x 4 + E 100 mg daily. Cycles were repeated q 4 weeks. Radiologic responses were measured with RECIST (study radiologist PB). Study endpoints: maximal tolerated dose, progression-free survival, response rate, toxicity and overall survival. RESULTS: 22 pts enrolled, 15 males, 2 prior Whipple, 20 PS 1, 2 PS 0. Median of 2 cycles (range 1-8) administered as of 9/09. Hematologic toxicity was common: grade 3 or 4 neutropenia (n=9) or thrombocytopenia (n=6). Other grade 3 toxicities: hyperglycemia (n=2), fatigue (n=2), ALT (n=3). Dose limiting toxicity reached in Arm B at dose level 2 (MK-0646 at 10 mg/kg + E + G): febrile neutropenia (n=1), hepatic transaminitis (n=1). Radiologic responses: 5 PR (including 1 hepatic CR), 7 PD, 8 SD, 1 not evaluated, 1 not treated. TTP range (based on 12 pts) was 4 to &amp;gt;36 weeks. Ranges for: IGF-1 levels, 28-280 ng/mL; IGFBP-3 levels, 900-4000 ng/mL. The range of IGF-1 to IGFBP-3 ratios for patients with PR and SD was .027-.036 versus a range of .034-.058 for patients with PD. CONCLUSION: MK-0646 is tolerable in a dose of 10 mg/kg with G 1000 mg/m2 and at 5 mg/kg with G 1000 mg/m2 and E 100 mg. Promising anti-tumor activity was noted. A randomized phase II study will be conducted with the control arm of G+E. 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 2760.
Abstract 3538: In vivo combination studies of PM01183 with alkylating, antimetabolites, DNA-topoisomerase inhibitors and tubulin binding agents
Authors: Ma José Guillén, Oscar Cataluña, Mandy Palomares, Raquel Lopez, Carmen Cuevas, Pablo M. Aviles
Journal: Cancer Research (2011)

Abstract PM01183 is a new synthetic tetrahydroisoquinoline alkaloid that binds to selected DNA sequences and promotes apoptosis by inducing double-strand breaks at nanomolar concentrations. PM01183 displays significant antitumor activity in several murine models of human cancer. PM01183 is currently in phase I/II clinical development for cancer treatment. Nonclinical combination studies are increasingly relevant during the development of any anticancer compound. As such, PM01183 was assayed in combination (two-drugs) with representatives of alkylating agents (dacarbazine, temozolomide and cisplatin), antimetabolites (5-FU and gemcitabine), DNA-topoisomerase inhibitors (irinotecan and doxorubicin) and tubulin binding agents (paclitaxel and vinorelbine). Different models were used depending on the combination explored: STS (HT1080) for dacarbazine; glioma (U-87 MG) for temozolomide; gastric (HGC-27) for cisplatin and 5-FU; pancreas (SW1990) for gemcitabine; colon (HT-29) and NSCLC (H460) for irinotecan; and ovarian (A2780) for doxorubicin, paclitaxel and vinorelbine. Athymic nu/nu mice bearing tumors (ca. 150 mm3) were randomly allocated to 13 treatment groups: i) placebo; ii) PM01183 at 4 different dose levels, namely MTD (0.180 mg/kg), 0.75MTD, 0.5MTD and 0.25MTD; iii) Compound to be combined, at 4 different dose levels MTD, 0.75MTD, 0.5MTD and 0.25MTD; and, iv) PM01183 plus the combined compound, administered with the combination at (1+1), (0.75+0.75), (0.50+0.50) and (0.25+0.25) of MTD ratios. The antitumor activity was followed by T/C, (change in tumor volume for each treated -T- and placebo -C- groups during placebo-treated survival period). Then, the fraction affected (Fa) by the treatment was calculated (1-T/C) and, the combination index (CI) by the CI-isobol method determined. Synergism (CI ≤ 1 at Fa &amp;gt; 0.8) was recorded when PM01183 was combined with dacarbazine (HT1080), cisplatin (HGC-27), 5-fluororacil (HGC-27), gemcitabine (SW1990), irinotecan (H460), doxorubicin (A2780), paclitaxel (A2780) and vinorelbine (A2780). 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 3538. doi:10.1158/1538-7445.AM2011-3538
PM-18 * EGFR-STAT3 ACTIVATES -CATENIN SIGNALING TO DRIVE NEUROFIBROMA INITIATION IN NF1, AND PLAYS A ROLE IN TUMOR MAINTENANCE
Authors: N. Ratner, V. Keng, D. M. Patmore, J. K. Kendall, E. Jousma, K. Choi, D. Fan, E. B. Schwartz, J. R. Fuchs, Y. Zou, M.-O. Kim, E. Dombi, D. E. Levy, J. A. Cancelas, A. Stemmer-Rachamimov, R. J. Spinner, D. A. Largaespada
Journal: Neuro-Oncology (2014)

To identify genes and signaling pathways that drive peripheral nerve tumor initiation and growth beyond the Ras-MAPK pathway we used unbiased insertional mutagenesis screening. We identified Stat3 as a potential driver of Neurofibromatosis type 1 neurofibroma. Targeted genetic deletion of Stat3 in Schwann cell precursors (SCPs) and Schwann cells (SCs) largely prevented neurofibroma formation, and self-renewal of tumor initiating cells. Genetic gain- and loss-of-function identified EGFR as the major upstream regulator of P-Stat3 in mouse and human neurofibroma SCP and in neurofibroma initiation; IL-6 reinforced EGFR/Jak/Stat signaling. Preclinical tests of a Jak2/Stat3 inhibitor reduced established neurofibroma growth, supporting an additional role for Stat3 in benign nerve tumor maintenance. Unexpectedly, downstream of Stat3, we identified β-catenin, and β-catenin expression rescued phenotypic effects of Stat3 loss in SCPs. Phosphorylated STAT3 (Y705) and β-catenin were strongly correlated in NF1 human plexiform neurofibromas. The data support testing of JAK/STAT inhibition and Wnt/ β-catenin pathway inhibition in neurofibroma therapeutic trials. Supported by: NIH R01 NS28840 to N.R. and NIH P50 NS057531 to N.R. and D.L.), a DAMD New Investigator Award (W81XWH-11-1-0259) and an Ohio State University Comprehensive Cancer Center Pelotonia Idea Grant (to J.W.). The American Cancer Society (IRG-67-003-44) supported J.R.F.