tbuckley/cabot-search huggingface dataset:
TRATAMIENTO ENDOSCÓPICO DE LA COLITIS ACTÍNICA. ANÁLISIS DE NUESTRA EXPERIENCIA
Authors: M Gómez Alonso, C Prieto Martínez, M Basterra Ederra, E Rubio Guindulain, M Garaigorta De Dios, J Vila Costas, J Jiménez Pérez
Journal: Endoscopy (2012)

Introducción: La incidencia de colitis actínica en los pacientes que han recibido radioterapia pélvica oscila del 2 al 20%. La manifestación clínica más frecuente es la hemorragia. El tratamiento endoscópico más utilizado es la aplicación de argón plasma, por su efectividad y por su bajo número de complicaciones. Objetivo: Valorar la respuesta clínica tras el tratamiento con argón plasma en los pacientes con colitis actínica. Material y método: Análisis retrospectivo descriptivo de las endoscopias digestivas bajas realizadas en nuestro centro por colitis actínica entre enero de 2009 y junio de 2012.La gravedad de la rectorragia se ha valorado según la clasificación de Chutckan. La respuesta clínica se define como el cese de la rectorragia tras el tratamiento. Los datos se han analizado con el programa SPSS versión 17,0. Resultados: En este periodo se diagnosticaron un total de 70 casos de colitis actínica, recibiendo tratamiento endoscópico con argón un 28,6% (20 pacientes). De ellos, 90% eran varones. El 80% eran mayores de 65 años. El tumor más frecuente por el que se había administrado la radioterapia era el de próstata (85%). La radioterapia administrada fue externa en el 75%. El 61% habían recibido una dosis acumulada de radiación >50Gy. El 35% recibía tratamiento anticoagulante y el 25% antiagregante. Un 10% padecía afectación del recto y de los primeros centímetros del sigma y el resto únicamente afectación rectal. El 60% había presentado una hemorragia moderada y el 20% había precisado transfusión. La mediana del número de sesiones fue de 3 (rango 1–10). El éxito clínico se alcanzó en el 80%. No se produjo ninguna complicación. La mediana de seguimiento fue de 9 meses (rango 1–30). Conclusiones: El argón plasma es un tratamiento eficaz en el control de la rectorragia y la anemia producidas por la colitis actínica, con escasas complicaciones.
Abstract 5358: Epstein-Barr Virus-encoded BARF1 gene stimulates gastric epithelial cell MMP-1 secretion through ERK activation
Authors: Jin-Yong Jeong, Hyun-Jeong Byun, Jun Hee Woo, Chul Woo Kim, Woo Ho Kim, Mee Soo Chang
Journal: Cancer Research (2010)

Abstract The Epstein-Barr virus (EBV), originally isolated from Burkitt's lymphoma tissue, has now been associated with various epithelioid diseases and many other malignancies, including gastric adenocarcinoma. Our interest has been focused on the BARF1 early gene from EBV, which has ability to induce oncogenic transformation in rodent fibroblasts and to immortalize monkey kidney primary epitherial cells. The aim of this study was to investigate the effect of BARF1 expression in gastric cancer cells. First, a pEGFP vector containing the full length BARF1 gene was constructed and transfected into EBV negative gastric cancer cell lines (AGS and SNU601). Microarray analysis was then performed and gene expression profiles were analyzed and compared between the cell containing full length BARF1 gene and the vector control. We found that matrix metalloproteinase-1 (MMP-1) was significantly up-regulated in the cell containing BARF1 gene. The MMP-1 mRNA and protein expression levels are confirmed by RT-PCR and Western blotting. Additionally, the mobility of BARF1 transfectants was increased in scrape-wound migration assay compared with the vector control cells. Because MMP-1 secretion in other cell types is extracellular signal regulated kinase (ERK)-dependent, we examined mitogen-activated protein kinase (MAPK) ERK activation in response to BARF1. BARF1 also induced activation of ERK. To determine whether BARF1-induced MMP-1 secretion was ERK-dependent, we used PD98059 and UO126, the specific inhibitors of MEK, the proximal activator of ERK. UO126 and PD98059 inhibited ERK activation and MMP-1 secretion, indicating that MMP-1 secretion in response to BARF1 was MEK- and ERK-dependent. Because p38 activity mediates MMP-1 secretion in dermal fibroblasts and several other cell types, but inhibits MMP-1 secretion in cytokine-stimulated AGS cells, we also examined the effects of p38 inhibition on MMP-1 secretion in response to BARF1. p38 inhibition with the specific p38 inhibitors, SB203580 and SB202190, enhanced MMP-1 secretion, as well as ERK activation. These results indicate that EBV-encoded BARF1 gene stimulates gastric epithelial cell MMP-1 secretion via ERK activation. This is the first report that a viral protein, BARF1, is capable of regulating MMP-1. 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 5358.
Lung Cancer Metastases to Lymph Nodes at Celiac Axis is Common and EUS-FNA plays a Critical role for Detection of the Metastases
Authors: P Singh, R Gupta, P Mukhopadhyay, Y Jadhav, B Camazine, A Khan, Y Yaqub, R Erickson
Journal: Endoscopy (2006)

Background: Esophageal cancer metastases to lymph node at celiac axis (CLN) are associated with poor survival. Aim: To determine: 1) incidence of metastases to CLN in lung cancer; 2) sensitivity of the EUS-FNA and CT scan for the detection of the metastases to CLN; and, 3) the prognostic significance of metastases to CLN. Methods: Data from an ongoing prospective study at our institution were used. Consecutive subjects with newly diagnosed lung cancer underwent EUS examination and EUS-FNA of CLN was performed whenever nodes of any size could be identified. Results: Of 113 cases with lung cancer, metastases to the CLN were detected in 12 cases. The sensitivity of EUS-FNA for the detection of the metastases to the CLN was significantly higher than the CT scan (100% vs. 50%; p=0.03). Univariable analysis showed metastases to mediastinum, liver, adrenal gland and CLN, staging, curative surgery, and chemotherapy as significant predictors of survival. The median survival time in subjects with and without EUS-evidence of metastases to CLN was 142.5 days (95% CI 94,263) and 330 days (95% CI 283, 421). The difference was statistically significant (p=0.002). Cox-PH model showed metastasis to celiac axis and liver as independent predictor of poor survival (p=0.02). Conclusion: Lung cancer metastases to CLN are common (11%) and are an independent predictor of poor survival. The sensitivity of the EUS-FNA for the detection of the metastases to CLN is superior to the CT scan. We recommend EUS evaluation of the celiac axis for the complete and accurate staging of lung cancer.
Abstract 1608: Novel lipogenic enzyme ELOVL7 is involved in prostate cancer growth through saturated long-chain fatty acid metabolism
Authors: Kenji Tamura, Asami Makino, Francoise Hullin-Matsuda, Toshihide Kobayashi, Mutsuo Furihata, Suyoun Chung, Shingo Ashida, Tsuneharu Miki, Tomoaki Fujioka, Taro Shuin, Yusuke Nakamura, Hidewaki Nakagawa
Journal: Cancer Research (2010)

Abstract A number of epidemiologic studies have indicated a strong association between dietary fat intake and prostate cancer development, suggesting that lipid metabolism plays some important roles in prostate carcinogenesis and its progression. In this study, through our genome-wide gene expression analysis of clinical prostate cancer cells, we identified a novel lipogenic gene, ELOVL7, coding a possible long-chain fatty acid elongase, as overexpressed in prostate cancer cells. ELOVL7 expression is regulated by the androgen pathway through SREBP1, as well as other lipogenic enzymes. Knockdown of ELOVL7 resulted in drastic attenuation of prostate cancer cell growth, and it is notable that high-fat diet promoted the growth of in vivo tumors of ELOVL7-expressed prostate cancer. In vitro fatty acid elongation assay and fatty acid composition analysis indicated that ELOVL7 was preferentially involved in fatty acid elongation of saturated very-long-chain fatty acids (SVLFA, C20:0). Lipid profiles showed that knockdown of ELOVL7 in prostate cancer cells affected SVLFAs in the phospholipids and the neutral lipids, such as cholesterol ester. Focusing on cholesterol ester as a source of de novo steroid synthesis, we show that ELOVL7 affected de novo androgen synthesis in prostate cancer cells. These findings suggest that EVOLV7 could be involved in prostate cancer growth and survival through the metabolism of SVLFAs and their derivatives, could be a key molecule to elucidate the association between fat dietary intake and prostate carcinogenesis, and could also be a promising molecular target for development of new therapeutic or preventive strategies for prostate cancers. 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 1608.
BCR-ABL-Expressing Cells Transduced with the HSV-tk Gene Die by Apoptosis upon Treatment with Ganciclovir
Authors: Carmen Rivas, Angela R.-M Miller, Manuel Collado, Eric W.-F Lam, Jane F Apperley, Junia V Melo
Journal: Molecular Therapy (2001)

The potential efficacy of prodrug activation of a transduced suicide gene in a cancer cell may be impaired or enhanced by oncoproteins produced by that cell. In the context of a gene therapy protocol for chronic myeloid leukemia (CML) we examined whether the Bcr-Abl fusion protein would have either of these effects. Thus, the mechanism of cell killing by transfer of herpes simplex virus thymidine kinase (HSV-tk) and subsequent ganciclovir (GCV) treatment was examined in pre-B (TonB210.1) cells and myeloid cells (32D) and in their BCR-ABL-expressing counterparts. HSV-tk-transduced cell lines, either in the presence or in the absence of BCR-ABL expression, became susceptible to GCV at concentrations which were nontoxic to the nontransduced cells. This susceptibility was represented by apoptotic cell death in all cases. Apoptosis was observed after 24 h of treatment with GCV in the tk-transduced parental cells and in the BCR-ABL-expressing TonB210.1 cells but only after a delay of more than 24 h in the 32Dp210 cells compared to 32D. Cell death in the BCR-ABL-expressing clones was preceded by S- and G2/M-phase cell cycle arrest. Activation of FAS/APO-1 and caspase-8 was observed in all the tk-transduced cell lines after GCV treatment. However, the caspase-8 inhibitor Z-IETD-FMK only partially abrogated tk/GCV-induced apoptosis. A possible role for inhibition of Bcl-2 or Bcl-x(L) expression in the apoptosis induced by GCV was observed in the tk-transduced TonB210.1 cells but not in the 32D or 32Dp210 cells. The data demonstrate that expression of the Bcr-Abl oncoprotein does not block the apoptosis induced by the HSV-tk/GCV system, suggesting that this suicide gene therapy strategy could be considered for the treatment of CML in blast crisis.
VSV-G Envelope Glycoprotein Forms Complexes with Plasmid DNA and MLV Retrovirus-like Particles in Cell-free Conditions and Enhances DNA Transfection
Authors: Tatsuya Okimoto, Theodore Friedmann, Atsushi Miyanohara
Journal: Molecular Therapy (2001)

We have previously shown that vesicles containing the spike glycoprotein of the vesicular stomatitis virus (VSV-G) can associate efficiently with immature, non-infectious, envelope-deficient retrovirus-like particles assembled by packaging cells to produce infectious, pseudotyped viruses in cell-free conditions in vitro. We have also previously reported that VSV-G can enhance DNA lipofection efficiency by interacting with liposomes to form fusogenic, serum-stable liposomes with enhanced transfection properties. Here, we report that VSV-G can form a complex directly with naked plasmid DNA in the absence of a lipofection reagent and can thereby enhance the transfection efficiency of the naked plasmid vector. Sucrose gradient sedimentation analysis demonstrated that VSV-G can also associate with plasmid DNA and murine leukemia virus (MLV) gag-pol particles to form ternary complexes that co-sediment with high DNA transfecting activity. The increased transfection efficiency with VSV-G was dependent on the presence of the polycation (Polybrene) in the culture medium during transfection. Enhanced transfection was abolished by a neutralizing antibody to VSV-G. These results may be useful in the study of retrovirus assembly, in the further design of hybrid DNA-based retrovirus-like vectors, and in the full in vitro, cell-free assembly of infectious virus-like particles from component parts.
PWE-159 Hif-1Alpha-Dependent Gastrin Gene Expression Mediates Resistance to Hypoxia-Inducible Apoptosis in a Human Colorectal Cancer Cell Line
Authors: D A Westwood, O Patel, A Shulkes, C Christophi, G S Baldwin
Journal: Gut (2013)

<h3>Introduction</h3> Understanding the molecular processes mediating colorectal cancer (CRC) tumorigenesis will enable the development of targeted therapies that selectively disrupt the pathways responsible for tumour growth. The gastrin family of growth factors promote CRC growth, invasion and angiogenesis. Hypoxic microenvironments, caused by tumours outgrowing their local blood supply, stimulate aggressive tumour behaviour. However, the effect of hypoxia on gastrin expression in CRC is unknown. <h3>Methods</h3> Expression of the gastrin gene in the CRC cell line LoVo was examined under conditions of normoxia and hypoxia. The effect of inhibiting expression of HIF-1α (the transcriptional master regulator of cellular responses to hypoxia) and of deleting HIF-binding sites in the gastrin promoter was investigated. The effect of inhibiting gastrin expression on CRC cell behaviour <i>in vitro</i> and on tumorigenesis in mouse xenografts was analysed. <h3>Results</h3> Gastrin gene expression in CRC cells is stimulated by hypoxia by HIF-1α binding to the gastrin promoter. The viability of hypoxic (1% O2) gastrin knockdown cells <i>in vitro</i> is diminished due to loss of resistance against hypoxia-inducible apoptosis. In xenografts in mice exposed to hypoxia (10% O2) for 21 days, apoptosis is significantly increased by knocking down gastrin expression. <h3>Conclusion</h3> This work provides evidence that gastrin expression is involved in the adaptation of CRCs to hypoxic microenvironments through resistance to apoptosis. Shrinkage of CRC liver metastases by the angiogenesis inhibitor bevacizumab is dependent on hypoxia-induced apoptosis. Therapies that target gastrin may enhance the therapeutic efficacy of bevacizumab and increase secondary resectability rates in patients with CRC liver metastases. <h3>Disclosure of Interest</h3> None Declared.
A6.6 In RA patients, antibodies to the citrullinated peptide EBNA35-58Cit from epstein-barr nuclear antigen-1 crossreact with the citrullinated fibrin peptide β60-74Cit60,72,74
Authors: M Cornillet, E Verrouil, A Cantagrel, G Serre, L Nogueira
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Among the Rheumatoid Arthritis (RA)-specific antibodies to citrullinated proteins/peptides (ACPA), the autoantibodies to citrullinated fibrinogen (AhFibA) target 2 immunodominant epitopes borne by the peptides α36-50Cit<sub>38,42 </sub>and β60-74Cit <sub>60,72,74</sub>. RA sera also contain antibodies to the citrullinated peptide EBNA35-58Cit derived from EBNA-1, a protein of Epstein Barr Virus (EBV). <h3>Objectives</h3> To analyse the diagnostic value of anti-EBNA35-58Cit antibodies and their relationships with AhFibA, anti-α36-50Cit<sub>38,42 </sub>and anti-β60-74Cit<sub>60,72,74</sub> autoantibodies. <h3>Methods</h3> A large representative series of 181 established RA and 436 non-RA rheumatic diseases was tested by ELISA for AhFibA, anti-CCP2, anti-α36-50Cit<sub>38,42, </sub>anti-β60-74Cit<sub>60,72,74</sub> and anti-EBNA35-58Cit antibodies. Diagnostic indexes, correlations and concordances between tests were analysed. In addition, cross-reactivity of anti-EBNA35-58Cit toward β60-74Cit<sub>60,72,74</sub> and α36-50Cit<sub>38,42 </sub>was evaluated in competition assays. <h3>Results</h3> At a diagnostic specificity of 98.5%, the diagnostic sensitivity of anti-EBNA35-58Cit antibodies was 36%, similar to that of anti-α36-50Cit<sub>38,42 </sub>(41%) but significantly lower than that of anti-β60-74Cit<sub>60,72,74</sub> (62%) autoantibodies. Moreover, almost all sera containing anti-EBNA35-58 antibodies were reactive to citrullinated fibrinogen, 91% to β60-74Cit<sub>60,72,74,</sub> and 43% to α36-50Cit<sub>38,42</sub>. Anti-EBNA35-58 antibodies titres significantly correlated with those of anti-β60-74Cit<sub>60,72,74</sub> (r = 0.482), AhFibA (r = 0.504) and anti-CCP2 (r = 0.479) but not with those of anti-α36-50Cit<sub>38,42 </sub>(r = 0.051). Competition assays revealed that anti-EBNA35-58Cit antibodies are highly crossreactive with anti-β60-74Cit<sub>60,72,74</sub> but not with anti-α36-50Cit<sub>38,42 </sub>autoantibodies. <h3>Conclusions</h3> Anti-EBNA35-58Cit antibodies are present in 36% of AhFibA-positive patients with established RA. They are highly crossreactive with the autoantibodies to the immunodominant fibrin peptide β60-74Cit<sub>60,72,74. </sub>That suggests that the two antibodies have the same fine specificity and therefore correspond to a same subpopulation of ACPA.
High dose estrogen as a salvage hormonal strategy for highly refractory metastatic breast cancer (MBC): “back to the future.”.
Authors: RL Mahtani, A Stein, CL Vogel
Journal: Cancer Research (2009)

Abstract Abstract #6129 High dose estrogens are an efficacious but widely ignored treatment option for patients with MBC. This is due in part to the introduction of tamoxifen, which was shown to be equivalent in efficacy with fewer side effects in the 1970's. After local Institutional Review Board approval we identified 26 patients with MBC treated in our practice with either diethylstilbestrol (15mg/day) or estradiol, generally, at a dosage of 30mg daily. One patient remains too early to evaluate. The median age at initial diagnosis was 46 and median age for patients at the start of high dose estrogen therapy was 59. All but 2 patients had confirmed hormone receptor positive tumors (one with a very long disease free interval and the other, prior response to hormonal therapy). Two of 26 patients were HER-2neu + by FISH analysis. The median # of sites of disease was 2 (range 1-3) and 50% had dominant visceral disease. Patients had received a median of 3 prior chemotherapy regimens (range 0-7), and 4 prior hormonal regimens (range 1-7), for a median of 7 prior systemic therapies (range 0-12). The median distant disease free interval (DFI) was 62 months (range 0 to 264 months). The median time from recurrence to initiation of estrogen therapy was 57 months (range 1 to 132 months). Six of 25 (24%) currently evaluable patients had objective anti-tumor responses, with one having a complete response in liver of 22 months. In addition, 4 of 25 patients (16%) with less clearly measurable disease had prolonged stable disease for ≥ 6months (7, 9, 13, and 14months, respectively). Clinical benefit (defined as CR, PR, and prolonged SD ≥6months) was 40%, with median duration of 9 months (mean of 12). Two patients are in continuing remission at 7 and 14months, respectively. Toxicities included vaginal bleeding in 7 of 25 (6 grade 1 and 1 grade 2), nausea in 4, and fluid retention in 8 (7 grade 1 and 1 grade 2). The patient with grade 2 fluid retention responded to a dose reduction to 6mg daily. Only 3 of 25 of patients discontinued estrogen therapy due to toxicity (1 vaginal bleeding, 1 refused to continue, and 1 nausea). In addition, one of the 3 patients that discontinued due to toxicity had a prolonged estrogen withdrawal response of 12months duration after 9 months of stable disease. Conclusion: Almost all patients with hormone receptor (+) MBC eventually develop resistance to endocrine agents. These data confirm the efficacy of high dose estrogens as yet another option for heavily-treated patients in whom further endocrine manipulation might still be appropriate. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6129.
THU0198 Serum angiopoietin-2 level strongly reflects the disease activity and renal function in ANCA-associated vasculitis
Authors: Y. Wada, Y. Nozawa, H. Sato, T. Nakatsue, S. Murakami, T. Kuroda, M. Nakano, I. Narita
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Angiopoietin-2 (Ang-2) has emerged as a key mediator of endothelial cell activation. Ang-1 and Ang-2 are antagonistic ligands which bind with similar affinity to the extracellular domain of the tyrosine kinase with Ig-like and epidermal growth factor-like domains 2 (Tie-2) receptor, which is almost exclusively expressed by endothelial cells. Ang-1/Tie-2 signalling maintains vessel integrity, inhibits vascular leakage, suppresses inflammatory gene expression and prevents recruitment and transmigration of leukocytes. In contrast, binding of Ang-2 disrupts protective Ang-1/Tie-2 signalling and facilitates endothelial inflammation. Recently, serum Ang-2 levels have been reported to be elevated in autoimmune disorders such as rheumatoid arthritis, systemic lupus erythematosus, and ANCA-associated vasculitis (AAV). <h3>Objectives</h3> To examine the serum Ang-2 levels in patients with AAV, and investigate the relationship with the clinical and laboratory findings. <h3>Methods</h3> Fifty-nine patients with AAV (microscopic polyangitis (n=27), polyangitis with granulomatosis (n=15), Churg-Strauss syndrome (n=14), others (n=3)), who had been referred to Niigata University Medical and Dental Hospital between 2000 and 2011, were participated in this study. Written informed consent was obtained from each participant.The patients were divided into 2 groups according to their disease activities using <i>Birmingham</i>vasculitis activity score (BVAS) (active disease group (AD group, n=45) and remission disease group (RD group, n=14)). Serum Ang-2 levels and laboratory findings were examined in each subject. The data from all subjects were also analyzed using Spearman's rank correlation coefficient to determine the relationship with serum Ang-2 levels. <h3>Results</h3> The serum Ang-2 level, C-reactive protein (CRP), white blood cell count, and urinary protein excretion were significantly higher in patients with AD group compared with those with RD group. In Spearman's rank correlation coefficient analysis using data from all subjects, the serum Ang-2 level was positively correlated with BVAS (r=0.62, p&lt;0.0001), CRP (r=0.47, p=0.0003), serum creatinine (r=0.38, p=0.005), and urinary protein excretion (r=0.55, p&lt;0.0001), and negatively correlated with estimated glomerular filtration rate (r=-0.37, p=0.005). <h3>Conclusions</h3> Serum Ang-2 level was strongly correlated with the disease activity and renal function in AAV. These results indicated the possible role of Ang-2 in the development of AAV through endothelial injuries. <h3>References</h3> P Kümpers, et al. Ann Rheum Dis 2009; 68: 1638-43. P Kümpers, et al. Nephrol Dial Transplant 2009; 24: 1845-50. J Westra, et al. Rheumatology 2011; 50: 665-73. <h3>Disclosure of Interest</h3> None Declared