tbuckley/cabot-search huggingface dataset:
Abstract 2188: Effect of the protein complex formation of a novel tumor suppressor HLJ1 and nuclear protein p54nrb on human lung adenocarcinoma cell migration and invasion
Authors: Sheng-Yi Lin, Ching-Hsien Chen, Sung-Liang Yu, Chi-Chung Wang, Gee-Chen Chang, Jeremy J. W. Chen
Journal: Cancer Research (2011)

Abstract Lung cancer is the most common cause of cancer deaths in the world, and the incidence is increasing each year. In the previous studies, we have identified and characterized a novel tumor/invasion suppressor gene HLJ1 (human liver DnaJ-like protein, also called DNAJB4) in a lung cancer cell line model with different invasion capability. However, the suppressive mechanism of HLJ1 is unclear. Therefore, the objective of this study is to investigate and characterize the proteins interacting with HLJ1. To obtain the novel HLJ1-binding protein, the differentially cultured density of tumor cell is employed to mimic metastatic characteristics in vitro. We identified two proteins, p54nrb and PSF, that can interact with HLJ1 in high cell culture density by immunoprecipitation assay and MALDI-TOF analysis. The complex of HLJ1 and p54nrb was confirmed in vitro and in vivo by co-immunoprecipitation, GST pull-down and mammalian two-hybrid assay. In addition, the results of GST pull-down assay indicated that p54nrb can interact with HLJ1 through HTH motif. We also found that the expressions of both HLJ1 and p54nrb are increased in A549, CL1-0, CL1-5 and CL1-5F4 cancer cell lines while are culturing in high cell density. The results of immunofluorescent staining and cytosolic/nuclear protein fraction revealed that p54nrb is mainly located in the nucleus. Furthermore, we found that over-expression of p54nrb protein in the highly invasive lung cancer cell line, CL1-5, can reduce cancer cell proliferation, colony formation, invasion and migration. On the other hand, p54nrb was decreased when most cells are in DNA synthesis phase. Once over-expression of p54nrb in CL1-5 cell line, the cell cycle would arrest in G1 phase to reduce cancer cell proliferation. Investigating the action mechanism of HLJ1-p54nrb interaction is important, it may not only provide a new insight to understand the pathway of metastasis and growth regulation but also be as the new target molecule for anti-cancer therapy in the future. 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 2188. doi:10.1158/1538-7445.AM2011-2188
P454Vascular abnormalities in spontaneously hypertensive rats: a matter of substrains
Authors: E N T P Bakker, G Groma, LJA Spijkers, H Van Veen, V Everts, A Jongejan, PD Moerland, SM Arribas, E Vanbavel
Journal: Cardiovascular Research (2014)

Introduction: Spontaneously hypertensive rats (SHR) have been used frequently as a model for human essential hypertension. However, both the SHR and its normotensive control, the Wistar Kyoto rat (WKY), consist of genetically different sublines. We tested the hypothesis that discrepant data in literature regarding the pathophysiology of vascular remodeling in hypertension result from the use of different rat sublines.
P601 CCR6 DEFICIENCY ENHANCES LIVER INFLAMMATION AND FIBROSIS BY MODULATING HEPATIC MACROPHAGES M1/M2 BALANCE AND INFLAMMATORY CELLS RECRUITMENT
Authors: S. Affò, D. Rodrigo-Torres, D. Blaya, O. Morales-Ibanez, C. Millán, V. Arroyo, J. Caballería, P. Ginès, R. Bataller, P. Sancho-Bru
Journal: Journal of Hepatology (2014)
Abstract 2548: Quantitative changes in endogenous DNA adducts correlate with conazole mutagenicity and tumorigenicity in mouse liver
Authors: Jeffrey A. Ross, Sharon A. Leavitt, Judith E. Schmid, Garret B. Nelson
Journal: Cancer Research (2012)

Abstract We have previously shown that the conazole fungicides triadimefon and propiconazole, which are tumorigenic in mouse liver, are in vivo mouse liver mutagens in the Big Blue™ transgenic mutation assay when administered in feed at tumorigenic doses. The nontumorigenic conazole myclobutanil was not mutagenic under the same conditions. DNA sequencing of the mutants recovered from each treatment group and from untreated control animals revealed that the mutations induced by propiconazole and triadimefon do not result from clonal expansion of background mutations. We hypothesized that these mutations arise from the accumulation of reactive electrophilic metabolic byproducts within the liver in vivo. We therefore measured the spectra of endogenous DNA adducts in the livers of mice from these studies in order to determine if quantitative or qualitative differences in DNA adducts correlated with mutagenicity and tumorigenicity. We resolved and quantitated 16 individual adduct spots by 32P postlabeling and thin layer chromatography using 3 solvent systems. Qualitatively, we observed the same DNA adducts in control mice as in mice receiving conazoles. However, the 13 adducts with the highest chromatographic mobility were, as a group, present at significantly higher amounts in the livers of mice treated with propiconazole and triadimefon than in their concurrent controls, whereas this same group of DNA adducts in the myclobutanil-treated mice was not different from controls. We hypothesize that this treatment-related increase in endogenous DNA adducts may explain the observed increased in vivo mutation frequencies previously reported to be induced by treatment with propiconazole and triadimefon. This abstract does not necessarily reflect EPA policy. 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 2548. doi:1538-7445.AM2012-2548
Surgical Treatment of Cancer of the Cervix Recurring after Primary Irradiation Therapy
Authors: Gilbert H. Friedell, Frank Cesare, Langdon Parsons
Journal: New England Journal of Medicine (1961)

THE proper management of carcinoma of the cervix persistent or recurrent at the local site or in the upper vagina after definitive radiation therapy has always been a discouraging problem. The most experienced radiotherapists have little enthusiasm for retreatment in this area when the initial treatment has been adequate.1 , 2 If it is thought that insufficient radiation was given originally, the therapist may elect to give the patient another course of radiation. In most other cases, however, recurrence indicates that the tumor is unresponsive, and any further radiation simply tends to make the patient miserable without increasing longevity.In some cases . . .
Abstract 430: 4F2hc mediates renal cancer cell (RCC) behavior
Authors: Marina Poettler, Waclawa Kalinowska, Rene Novotny, Kira H. Braemswig, Andrea Haitel, Martin Susani, Christoph C. Zielinski, Gerald W. Prager
Journal: Cancer Research (2011)

Abstract 4F2, a transmembrane protein, has a heteromeric structure, consisting of a heavy subunit (4F2hc, CD98hc, SLC3A2) and a light subunit, extracellular linked together via disulfid bounds. The light chains provide amino acid transport activity, while the heavy chain physically interacts with a conserved motif of integrin beta subunits, thereby mediating adhesion-induced signal transduction. A genetic knockout of 4F2hc in animals is embryonic lethal, overexpression of 4F2hc in somatic cells leads to malignant transformation. In the present study we aimed to characterize 4F2hc expression in renal cell cancer (RCC) as a diagnostic or prognostic marker, as well as to indentify a potential functional role of 4F2 in tumor cell behavior. By immunohistochemistry and analysis of multi tissue arrays, we found that 4F2hc is highly expressed in papillary, clear cell and chromophobe RCC, while no 4F2hc expression was found in benign tumors, such as oncocytomas. Thereby, 4F2hc expression directly correlated with grade of differentiation suggesting 4F2hc as a novel and reliable marker for the more malignant subtype II papillary renal cell cancer (type II 83.34 %, type I 4.76 % 4F2hc positive, p &amp;lt; 0.00001; n = 51). To evaluate a potential functional role of 4F2 in renal cancer cell behavior, we generated a stable low 4F2hc clear cell RCC cell line (93% downregulation) and compared the protein expression as well as the tumor cell behavior with a high expressing mock transfected counterpart cell line. We found that tumor cell behavior such as cell proliferation, cell survival and cell migration were significantly impaired, whenever 4F2 expression was downregulated. As 4F2 light chain distribution to cell surface is dependent on 4F2hc, leucine amino acid transport in low 4F2hc/Caki2 cells is impaired, as shown by C14-leucine uptake assays. Transfection of silent mutations either lacking integrin interaction site (delta WALLL) or amino acid transport capabilities (Cys109_330Ser) in low4F2/ Caki2 cells revealed a functional relevance of 4F2hc upon tumor cell behavior. From these data we conclude that 4F2 (1) represents a promising new diagnostic marker for RCCs, whereby grade of differentiation correlates with amount of 4F2 expression, and (2) 4F2 might play a functional role in renal cancer cell behavior. 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 430. doi:10.1158/1538-7445.AM2011-430
A Comparison of Standard Cardiopulmonary Resuscitation and Active Compression–Decompression Resuscitation for Out-of-Hospital Cardiac Arrest
Authors: P Plaisance, K G Lurie, E Vicaut, F Adnet, J L Petit, D Epain, P Ecollan, R Gruat, P Cavagna, J Biens, D Payen
Journal: New England Journal of Medicine (1999)

We previously observed that short-term survival after out-of-hospital cardiac arrest was greater with active compression–decompression cardiopulmonary resuscitation (CPR) than with standard CPR. In the current study, we assessed the effects of the active compression–decompression method on one-year survival.
Abstract P2-06-03: Specific Transcriptional Response of Four Blockers of Estrogen Receptors on Estrogen-Modulated Genes in ZR-75-1 Breast Cancer Xenografts
Authors: E Calvo, V Luu-The, C Martel, F Labrie
Journal: Cancer Research (2012)

Abstract Introduction: Acolbifene (ACOL) is a novel compound completely free of estrogen-like activity in both the human and rat mammary gland and uterus. In previous studies, it was observed that ACOL could have a cytotoxic or tumoricidal rather only tumorostatic activity, with a lack of development of tumor resistance. The objective of the present study was to obtain information on the molecular basis of the tumoricidal properties of acolbifene, as well as on the identity of the genes potentially implicated in the resistance to tamoxifen (TAM). The specificity of action of ACOL was compared to the pure antiestrogen fulvestrant (FUL) as well as to tamoxifen (TAM) and raloxifene (RAL). Methods: The gene expression profile of the ZR-75-1 breast cancer xenografts was studied following treatment with ACOL, RAL, TAM and FUL. Ovariectomized female nude mice (10/group) bearing human ZR-75-1 breast cancer xenografts were supplemented with estrone (E1) (subcutaneous silastic implants) and were injected daily with the vehicle alone or 50 μg of ACOL, RAL, TAM or FUL for 6 months. Mice were killed 24h after the last injection and ZR-75-1 tumors were collected and processed for RNA extraction and microarray analyses (Affymetrix GeneChip U133 Plus 2.0). Results: Long-term exposure of ZR-75-1 xenografts to E1 causes a massive modulation of E1-responsive genes. When the antiestrogens were administered simultaneously with E1, some compound-specific prevention of the effect of E1 was observed. Globally, the efficacy of the compounds was ACOL&amp;gt;FUL or RAL&amp;gt;TAM. ACOL significantly prevented the effect of E1 on 195 responsive genes. Among these, the most enriched gene ontological group in Molecular Function was Receptor Activity, including ER, insulin, retinoid and thrombospondin receptor activity. One of the transcriptional repressors of the estrogen signaling pathway, the NKX31, was down-regulated by E1 and completely blocked by ACOL (fold-change −1.64 and 2.54, respectively). The most enriched biological processes were associated with mammary gland development, positive regulation of glucose metabolic processes and blood vessel morphogenesis. Between the genes implicated in cell death/apoptosis of breast cancer cells, the changes of expression of 57, 51, 48 and 31 genes were significantly neutralized by ACOL, RAL, FUL and TAM, respectively. Sixteen genes implicated in tumor resistance to TAM were significantly blocked by ACOL, including DEGS1, a gene implicated in the inhibition of EGF receptor biosynthesis. The other 15 genes in the group were up-regulated by E1, changes which were significantly blocked by ACOL. Conclusion: The present data offer a possible explanation for the potent tumoricidal action of acolbifene in human breast cancer xenografts, thus offering a new paradigm in the hormonal therapy of breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-06-03.
Abstract 2105: High Galectin-1 expression correlates with poor prognosis and is involved in epithelial ovarian cancer proliferation and invasion
Authors: Jeong-Won Lee, Ha-Jeong Kim, Hye-Kyung Jeon, Young Jae Cho, Young Ae Park, Jung-Joo Choi, Yoo-Young Lee, Chel Hun Choi, Tae-Joong Kim, Duk-Soo Bae, Byoung-Gie Kim
Journal: Cancer Research (2012)

Abstract Purpose: Galectin-1 (Gal-1) is a 14-kDa laminin-binding galectin involved in several biologic events including regulation of tumor proliferation and metastasis. In this study, we investigated the clinical significance of Gal-1 expression and its functional role in cell proliferation and invasion in epithelial ovarian cancer (EOC). Experimental Design: We evaluated the expression of Gal-1 in 52 serous, 11 endometrioid, and 3 mucinous type EOC tumor samples from 66 patients by immunohistochemistry. In vitro experiments were performed to determine the function of Gal-1 in cell survival, proliferation, and invasion in EOC cells using siRNA and anginex, a Gal-1 inhibitor, as well as recombinant Gal-1 protein. Results: Patients with strong Gal-1 peritumoral staining had poorer progression-free survival (PFS) than patients with weak peritumoral staining (P = 0.03). Inhibition of Gal-1 by siRNA or anginex resulted in the inhibition of cell growth and proliferation of HeyA8 and SKOV3ip1 cells. Moreover, the ability of cells to migrate was significantly reduced by treatment of cells with Gal-1 siRNA but was increased by treatment of cells with recombinant Gal-1. When we evaluated the interaction between fibroblasts (H HESC) and cancer cells (A2780-CP20), we found that MMP-2 expression in cancer cells was affected by Gal-1 secreted by fibroblast cells, which suggests that Gal-1 in human fibroblasts might affect the invasive abilities of tumor cells. Conclusion: Our results suggest that Gal-1 expression is a potential prognostic factor for PFS and that Gal-1 could be a novel treatment target in EOC patients. 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 2105. doi:1538-7445.AM2012-2105
THU0439 Bacterial Identification and Bad Prognostic Factors During Infectious Spondylodiscitis
Authors: P. Guyader, A. Bisson-Vaivre, M. Verdet, A.-C. Bouyeure, S. Micu, D. Alcaix, O. Vittecoq, X. Le Loët, C. Zarnitsky, V. Goëb
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Define the most relevant investigations to define the organism(s) involved in infectious spondylodiscitis and put in evidence the risk factors of poor outcome (death, relapse, recurrence) or after-effects at middle-term and long-term. <h3>Methods</h3> Retrospective bicentric study on 306 patients affected by an infectious spondylodiscitis and followed-up between 2000 and 2009. Study on medical records and systematic telephonic call of patients and/or general practitioner. An uni and multivariate statistical analysis was performed. <h3>Results</h3> The probability to isolate an organism was significantly lower when there was no fever (p&lt;0,01; OR= 2,19 [1,23-3,94] or no inflammatory syndrome (p&lt;0,01; OR=3,35 [1,27-8,81] as well as a recent spine surgery (p&lt;0,001; OR=0,29 [0,16-0,55]), antibiotic exposure (p&lt;0,01; OR=0,43 [0,23-0,78]) or malignancy past history (p&lt;0,01; OR=0,42 [0,22-0,81]. A percutaneous discal and vertebral biopsy (PDVB) (p&lt;0,0001; OR=0,29 [0,16-0,55]) even with PCR analysis (p&lt;0,0001; OR=0,17 [0,08-0,36]) was not associated with a better probability to identify the germ. The diagnostic delay was significantly longer in the group of patients without isolated organism (p&lt;0,01). An initial neurologic trouble (p&lt;0,0001), an elevated age (p&lt;0,0170), liver cirrhosis (p&lt;0,01; OR=6,4 [1,74-19,05]) or epidural abscess (p&lt;0,001; OR=3,07 [1,42-6,61]) were significant and independent factors of poor outcome. Back (p&lt;0,01; OR=2,36 [1,28-4,34]) and radicular pains (p&lt;0,01; OR=2,73 [1,46-5,10]), a recent spine surgery (p&lt;0,01; OR=2,85 [1,50-5,37]) were associated to back pain sequelae at middle-term. They were significantly associated to spine stiffness (p&lt;0,001; OR=2,85 [1,50-5,37]), persistant neurologic trouble (p=0,0365; OR= 2,62 [1,03-6,65]) or disc injury (p&lt;0,001; OR=2,85 [1,50-5,37]). Long-term pain was significantly more frequent when the spondylodiscitis began after a back surgery (p&lt;0,02; OR=3 [1,09-8,23]). <h3>Conclusions</h3> The probability to isolate an organism was lower when clinical and biological presentations were less severe. However, the antibiotic therapy allowed similar vital and functional prognostic even if the the organism was identified or not. Our results also showed that a second PDBV or even a chirurgical biopsy were not justified. <h3>References</h3> Spilf. Primary infectious spondylodiscites, and following intradiscal procedure, without prosthesis. Recommendations. <i>Med Mal Infect</i>2007;37:269-77. Zimmerli W. Clinical practice. Vertebral osteomyelitis. <i>N England J Med</i>2010;362:1022-9 O'Daly BJ. Long-term functional outcome in Pyogenic spinal infection. <i>Spine (Phila Pa 1976)</i> 2008;33:246-53 <h3>Disclosure of Interest</h3> None Declared
SAT0446 A Meta-Analysis to Assess the “Real” Placebo Effect in Juvenile Idiopathic Arthritis (JIA)
Authors: S. Lanni, F. Bovis, E. Demirkaya, R. Galasso, A. Ravelli, A. Martini, N. Ruperto, A. Pistorio
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Juvenile idiopathic arthritis (JIA) is the more common chronic arthritis of childhood, and can lead to significant long-term morbidity, including physical disability. Treatment of the disease has greatly improved short and medium-term outcomes, and its effectiveness has been often tested with trials using placebo as comparator. However, until now the real magnitude of placebo effect has not been quantified in children with JIA. <h3>Objectives</h3> To estimate the placebo effect in JIA through a meta-analysis on phase III trials which compares the active compound versus placebo using different study designs (parallel or withdrawal). <h3>Methods</h3> The systematic literature search was carried out from June to December 2012 using publications retrieved in Medline, Cochrane Controlled Trials, ClinicalTrials.gov registers. The study was developed according to the PRISMA statement. For parallel design studies the outcome was evaluated as a single one-dimensional (OD) variable or, when available, as a composite score (CS); withdrawal studies were evaluated only by CS. <h3>Results</h3> A total of 23 trials were included in the final meta-analysis. In the seven OD studies, 38% (95% CI: 32-43%) of patients responded to placebo. Considering CS parallel trials, the rate of response to placebo was high in studies enrolling different JIA categories (38%; 95% CI: 33-43%) and lower in studies with only systemic included (13%; 95% CI: 6-20%). In withdrawal design trials, the percentages of placebo patients who flared during the double blind phase in the placebo arm was lower in the studies recruiting various JIA subgroups (62%; 95% CI: 50-74%) than trials with only a population of systemic subjects (67%; 95% CI: 37-97%) with substantial evidence of heterogeneity. <h3>Conclusions</h3> A sizable number of patients seems to benefit from placebo treatment. The placebo effect is mainly influenced by the study design and the rate of systemic patients enrolled. <h3>References</h3> Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009 July 21;6(7):e1000097. <h3>Disclosure of Interest</h3> None Declared
Abstract 1245: Hepatitis B virus X protein induces Src homology 2-containing protein tyrosine phosphatase, SHP2, expression through the NF-kB pathway in HBV-infected hepatocellular carcinomas
Authors: Hyun Mi Kim, Ga-hye Kim, Eunsil Yu, Jene Choi
Journal: Cancer Research (2012)

Abstract Hepatitis B virus X protein (HBx) has a crucial role in the development of hepatocellular carcinoma and activates many transcription factors, including AP-1, NF-kB and CREB. In the present study, we showed that increased SHP2 expression was observed in 16 (53%) of the 30 cases of HBV-positive hepatocellular carcinomas tissues. We investigated the relationship of SHP2 and HBx in stably HBx-overexpressing Huh7-X and transiently HBx expressing HEK293 cells. The level of SHP2 proteins was concomitantly increased with HBX in a dose-dependent manner in HEK293 cells. We identified a putative NF-kB binding site within 500 bp of the SHP2 promoter and also observed the decrease of SHP2 proteins after the treatment of the NF-kB/p65 inhibitor, parthenolide in HBx expressing cell. In addition, we confirmed that the complex of NF-kB and HBx proteins direct bound to the SHP2 promoter by chromatin immunoprecipitation (ChIP)-real time PCR assays. Taken together, we conclude that HBV infection induces SHP2 overexpression through the HBx-NF-kB pathway. Currently, we are investigating the effects of SHP2 overexpression in the proliferation of hepatocellular carcinoma cells. 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 1245. doi:1538-7445.AM2012-1245