tbuckley/cabot-search huggingface dataset:
The ENKI-2 water-jet system versus Dual Knife for endoscopic submucosal dissection of colorectal lesions: a randomized comparative animal study
Authors: Mihai Ciocîrlan, Mathieu Pioche, Vincent Lepilliez, Nicolas Gonon, Roland Roume, Guillaume Noel, Christian Pinset, Thierry Ponchon
Journal: Endoscopy (2013)

The ENKI-2 water-jet system for endoscopic submucosal dissection (ESD) combines submucosal saline pressure injection with dissection. The aim of this study was to compare ENKI-2 with a standard device in terms of procedure time and perforation rate during colorectal ESD.In this randomized comparative study, 10 30-mm-diameter lesions were created in the colon and rectum of 10 healthy adult pigs. The ESD procedure time and perforation rates were recorded for the ENKI-2 system and a standard Dual Knife method. Each pig had half the lesions dissected by ENKI-2 and half dissected by Dual Knife. One experienced and one inexperienced endoscopist took part in the study.A total of 95 lesions were dissected (47 by ENKI-2 and 48 by Dual Knife). The experienced endoscopist was able to excise comparably sized 30-mm lesions using both techniques. The dissection time was shorter for ENKI-2 (18.9 vs. 25.6 minutes; P = 0.034) and the perforation rate was lower compared with the Dual Knife (one perforation [4 %] vs. nine perforations [36 %]; P = 0.011). The inexperienced endoscopist performed significantly larger dissections using the ENKI-2 (934 ± 405 mm2 vs. 673 ± 312 mm2; P = 0.021) despite pre-marking similarly sized artificial lesions. Multivariate analysis demonstrated that for all lesions the dissection time was significantly longer for lesions in the proximal colon (P = 0.001) and the distal colon (P < 0.0001) and shorter for the experienced operator (P < 0.0001). ENKI-2 shortened the dissection time, but not significantly (P = 0.093).In experienced hands, the ENKI-2 system shortens dissection time and reduces the perforation rate. This effect was not statistically significant for an inexperienced operator. Dissection was faster in the rectum than the colon.
FRI0142 TNF-blocking therapy reduces cardiovascular disease and risk factors in rheumatoid arthritis:
Authors: A.M. van Sijl, I.M. Visman, M.J. Peters, C. van Dongen, Y.M. Smulders, A.E. Voskuyl, M.T. Nurmohamed
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Patients with rheumatoid arthritis (RA) are at increased risk of cardiovascular (CV) disease. The contribution of inflammation to this increased risk is well recognised. Recent register based studies indicate that suppression of tumour necrosis factor (TNF) lowers CV risk. No register to date has accurately assessed both CV- and RA-related parameters. <h3>Methods</h3> The CARRΈ study is a Dutch prospective cohort study of 353 randomly selected RA patients, aged 50-75, with 1381 patient years. The Biologics cohort is an ongoing study of 449 Dutch RA patients, also aged 50-75, with 1201 patient years of follow-up since their allocation to their first TNF-blocking agents adalimumab or etanercept. Fatal and non-fatal CV events (according to the international classification of disease, ICD-9) were documented in both cohorts. Cox-proportional hazard analyses were used to investigate the association between use of TNF-blocking agents and CV disease incidence. <h3>Results</h3> Incidence rate ratio of CV events in RA patients with TNF-blocking therapy versus those without TNF-blocking therapy was: 0.36 (95%&gt;confidence interval (CI): 0.18-0.73), incidence rate: 8.3 vs. 23.2 per 1.000 patient years, respectively. Age- and gender adjusted hazard ratio for CV disease incidence: 0.54 (95%&gt;CI: 0.24-1.21) in favour of patients receiving TNF-blocking therapy, although not statistically significantly so. The magnitude of this association remained stable after additional adjustment for CV risk factors, RA-related parameters and concomitant medication use. There was a difference in baseline characteristics between populations and there was no increase in CV risk factors over time in either group. Patients receiving TNF-blocking therapy, as expected, had a substantial improvement in RA-related parameters over time. <h3>Conclusions</h3> Our observations confirm the association between strong suppression of inflammation and curbing the CV risk in RA. Surprisingly, this CV risk appeared to be independent of CV risk factors. However, whether the reduced incidence of CV disease is due to allocation of patients with certain disease characteristics (more favourable CV risk profile in patients receiving TNF-blocking therapy) is not yet clear and may indicate channelling bias. <h3>Disclosure of Interest</h3> None Declared
Impact of Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis Vaccinations on Reported Pertussis Cases Among Those 11 to 18 Years of Age in an Era of Waning Pertussis Immunity
Authors: Tami H. Skoff, Stacey W. Martin
Journal: JAMA Pediatrics (2016)

There is accumulating literature on waning acellular pertussis vaccine-induced immunity, confirming the results of studies assessing the duration of protection of pertussis vaccines.To evaluate the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine's effect over time among those 11 to 18 years old, while accounting for the transition from whole-cell to acellular pertussis vaccines for the childhood primary series.Extended, retrospective analysis of reported pertussis cases between January 1, 1990, and December 31, 2014, in the United States. The analysis included all nationally reported pertussis cases.US Tdap vaccination program and the transition from whole-cell to acellular pertussis vaccines.Rate ratios of reported pertussis incidence (defined as incidence among 11- to 18-year-old individuals divided by the combined incidence in all other age groups) modeled with segmented regression analysis and age-specific trends in reported pertussis incidence over time.Between 1990 and 2014, 356 557 pertussis cases were reported in the United States. Of those, 191 914 (53.8%) were female and 240 665 (67.5%) were white. Overall incidence increased from 1.7 in 100 000 to 4.0 in 100 000 between 1990 and 2003, while latter years were dominated by epidemic peaks. Incidence was highest among infants younger than 1 year throughout the analysis period. Pertussis rates were comparable among all other age groups until the late 2000s, when an increased burden of pertussis emerged among children 1 to 10 years old, resulting in the second highest age-specific incidence. By 2014, 11- to 18-year-old individuals once again had the second highest incidence. While slope coefficients from segmented regression analysis showed a positive impact of Tdap immediately following introduction (slope, -0.4959; P < .001), a reversal in trends was observed in 2010 when rates of disease among 11- to 18-year-old individuals increased at a faster rate than all other age groups combined (slope, 0.5727; P < .001).While the impact of Tdap among adolescents looked promising following vaccine introduction, our extended analysis found that trends in adolescent disease were abruptly reversed in 2010, corresponding directly to the aging of acellular pertussis-vaccinated cohorts. Despite the apparent limitations of Tdap, it remains the best prevention against disease in adolescents.
566 STUDY OF HEPATITIS C VIRUS SUPERINFECTION AFTER LIVER TRANSPLANTATION BY ULTRA-DEEP PYROSEQUENCING
Authors: S. Perez-del-Pulgar, J. Gregori, P. Gonzalez, D. Garcia-Cehic, S. Ramirez, M. Cubero, J.I. Esteban, X. Forns, J. Quer
Journal: Journal of Hepatology (2013)
Abstract LB-318: Development of <i>Listeria monocytogenes-based</i> vaccine that concomitantly targets both the tumor cells as well as tumor vasculature
Authors: Anu Wallecha, Sandra Rivera
Journal: Cancer Research (2010)

Abstract Recently we described the development of Listeria monocytogenes (Lm) based chimeric human Her2/neu gene (ChHer2) harboring most of the known MHC class I epitopes of the HER2/neu oncogene (ChHer2) when expressed as a fusion protein to a non-hemolytic fragment of listeriolysin O. This construct when tested for immunogenicity and anti-tumor effects in mice proved to be efficacious in breaking immune tolerance toward the HER2/neu self-antigen and elicited strong T cell immune responses in experimental animals. These results support the further clinical development of this vaccine for treatment of HER2/neu overexpressing malignancies such as breast, colorectal and pancreatic cancers. Preclinical studies with three different Lm based vaccines targeting angiogenesis antigens have demonstrated potential in mediating the regression of tumors arising from distinct origin such as breast or skin cancer. Therefore, we hypothesized that the delivery of an angiogenic antigen simultaneously with a tumor-associated antigen will likely have a synergistic effect by impacting on tumor growth via targeting blood vessels while at the same time targeting a tumor specific antigen to enhance effector T cell infiltration in the tumor and improve the vaccine therapeutic efficacy. If true, this will result in a flexible platform by using different tumor antigens. We have created two dual recombinants Lm vaccines that express and secrete both the tumor specific antigen such as ChHer2 and tumor vasculature antigen such as High molecular weight melanoma associated antigen (HMW-MAA) successfully. Currently we are evaluating the anti-tumor effects and immune responses generated by these constructs. If successful, this study will have a great potential for human use in cancer immunotherapy. 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 LB-318.
Abstract LB-310: Changes in the gene expression profile of A375 human melanoma cells induced by over-expression of multifunctional pigment epithelium-derived factor
Authors: Benilde Jimenez, Jose L. Orgaz
Journal: Cancer Research (2012)

Abstract Pigment epithelium-derived factor (PEDF) is a broad-spectrum angiogenesis inhibitor that displays potent anti-metastatic activity in multiple tumor types. We have previously shown that PEDF prevents primary tumor growth and metastatic spread of human melanoma in mouse experimental models. Consistent with these observations, PEDF expression is lost at the late stages of melanoma progression, allowing melanoma cells to become angiogenic, migratory and invasive. PEDF's ability to modify the interplay between the host and tumor tissues strongly supports its use as a therapeutic agent for the treatment of metastatic melanoma. However, transition to the clinic requires a more detailed knowledge of the molecular mechanisms underpinning PEDF's activity. In this study we describe changes in the gene expression profile of A375 human melanoma cells induced by PEDF over-expression. PEDF modulated diverse categories of genes known to be involved in angiogenesis and migration. It downregulated cytokines like interleukin 8 and extracellular matrix proteins like collagen IV, while it upregulated fibronectin. Multiple transcripts previously described as contributing to the acquisition of malignant phenotype by melanoma were also diminished by PEDF over-expression, among which we validated galectin 3 and jagged 1. Additionally, PEDF downregulated S100β and melanoma inhibitory activity (MIA), which are widely used in the pathological diagnosis of melanoma. Interestingly, PEDF increased the expression of melanophilin and decreased rab27A, which are relevant targets for melanosome transport; suggesting that PEDF could directly impinge on melanocytic lineage-specific processes. Our study identifies new molecular targets and signaling pathways that may potentially contribute to determine PEDF's ability to restrict the aggressiveness of A375 human melanoma 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 LB-310. doi:1538-7445.AM2012-LB-310
THU0258 N-terminal pro-brain natriuretic peptide in a novel screening algorithm for pulmonary arterial hypertension in systemic sclerosis
Authors: V. Thakkar, W. Stevens, D. Prior, O. Moore, J. Byron, K. Patterson, P. Hissaria, J. Roddy, J. Zochling, J. Sahhar, P. Nash, K. Tymms, D. Celermajer, E. Gabbay, P. Youssef, S. Proudman, M. Nikpour
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Pulmonary Arterial Hypertension (PAH) is a major cause of mortality in SSc. N-terminal pro-brain natriuretic peptide (NT-proBNP) has emerged as a candidate biomarker that may enable the early detection of systemic sclerosis-related pulmonary arterial hypertension (SSc-PAH). <h3>Objectives</h3> To incorporate N-terminal pro-brain natriuretic peptide (NT-proBNP) into a screening algorithm for systemic sclerosis-related pulmonary arterial hypertension (SSc-PAH) that could potentially replace transthoracic echocardiography (TTE) as a less costly and more convenient “first tier” test. <h3>Methods</h3> NT-proBNP levels were measured in patients from 4 clinical groups: a group with right heart catheter (RHC) diagnosed SSc-PAH prior to commencement of therapy for PAH; a group at high risk of SSc-PAH based on TTE; a group with interstitial lung disease; and systemic sclerosis (SSc) controls with no cardiopulmonary complications. NT-proBNP levels were compared using ANOVA and correlated with other clinical variables using simple and multiple linear regression. ROC curve analyses were performed to determine the optimal cut-point for NT-proBNP and other clinical variables in prediction of PAH. <h3>Results</h3> NT-proBNP was highest in the PAH group compared to other groups (p&lt;0.0001), and higher in the risk group compared to controls (p&lt;0.0001). NT-proBNP was positively correlated with systolic pulmonary artery pressure (PAP) on TTE (p&lt;0.0001), and mean PAP (p=0.008), pulmonary vascular resistance (p=0.001) and mean right atrial pressure (p=0.006) on RHC. A composite model wherein patients screened positive if NT-proBNP ≥209.8pg/ml, and/or DLCO<sub>corr</sub> &lt;70.3% with FVC/DLCO<sub>corr</sub> ≥1.83, had a sensitivity of 100% and specificity of 77.8% for SSc-PAH. <h3>Conclusions</h3> We have proposed a screening algorithm for SSc-PAH, incorporating NT-proBNP level and PFTs. This model has high sensitivity and specificity for SSc-PAH and if positive, should lead to TTE and confirmatory testing for PAH. This screening algorithm needs to be validated prospectively. <h3>Disclosure of Interest</h3> None Declared
427 HIGH RATES OF HBsAg “a DETERMINANT” VARIABILITY AND IMMUNE ESCAPE MUTATIONS ARE ASSOCIATED WITH HBV REACTIVATION UPON IMMUNOSUPPRESSIVE THERAPY
Authors: R. Salpini, C. Alteri, V. Cento, A. Ricciardi, G. Maffongelli, M. Pollicita, C. Mirabelli, C. Sarrecchia, L. Sarmati, C. Mastroianni, M. Paoloni, M. Angelico, M. Andreoni, C.F. Perno, V. Svicher
Journal: Journal of Hepatology (2013)
Abstract 268: Regulation and function of ERBB3 signaling pathway in clear cell sarcoma
Authors: Yixiang Zhang, Ian J. Davis, Stephen P. Remillard, George D. Demetri, David E. Fisher, Andrew J. Wagner
Journal: Cancer Research (2010)

Abstract Clear Cell Sarcoma (CCS), a soft tissue malignancy of tendons and aponeuroses in children and young adults, is notoriously resistant to radiation and chemotherapy, and new approaches to treatment are needed. We recently demonstrated the involvement of the MET receptor tyrosine kinase (RTK) in regulation of the growth, migration, and invasion of CCS cells. However, pharmacologic agents targeting the HGF:MET axis could neither completely inhibit cell growth nor significantly induce apoptosis. To determine whether other RTKs might cooperate with MET in control of survival and proliferation of CCS cells, we used phospho-RTK arrays to assess the activation status of RTKs in three CCS cell lines (CCS292, DTC1, SU-CCS-1). We found that in addition to MET, ERBB3 was strongly activated in CCS. Western blot analysis confirmed constitutive activation of ERBB3 in CCS292 and DTC-1 cell lines and expression in all three lines. Since ERBB3 lacks intrinsic kinase activity, we searched for potential heterodimerization partners. Interestingly, we found that the activation of ERBB3 in different CCS cell lines relied on different partners: ERBB2 as a pivotal partner in CCS292, and MET as a pivotal partner in DTC-1. Moreover, we explored the possibility of a linkage between the CCS pathognomonic EWS-ATF1 fusion product and ERBB3 activation. We found that EWS-ATF1 knockdown resulted in both decreased expression of the ERBB3 ligand Neuregulin 1 and less ERBB3 phosphorylation in CCS292 cells, but had no effects on ERBB3 phosphorylation in DTC-1 cells. To explore the biological function of ERBB3, we applied siRNA or small molecule inhibitors of RTKs to CCS cell lines and determined the biological consequences by cell viability, cell cycle and apoptosis assays; these studies show that ERBB3 in conjunction with MET played an important regulatory role in the proliferation and survival of CCS cells. These data suggest that combined inhibition of the MET and EGFR signaling pathways may be a rationally designed strategy for treatment of patients with advanced CCS. 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 268.
Human Fetal Insulin Response to Sustained Maternal Hyperglycemia
Authors: S. Scott Obenshain, Peter A. J. Adam, Katherine C. King, Kaki Teramo, Kari O. Raivio, Niels Räihä, Robert Schwartz
Journal: New England Journal of Medicine (1970)

Hyperglycemia was maintained in normal mothers before delivery both at term and early in gestation to study the fetal pancreatic response to glucose. Normal controls and gestationally diabetic mothers were infused with saline. At term the human fetal pancreas responded to elevated blood glucose levels by increasing plasma insulin, and there was a direct correlation between blood glucose and plasma insulin concentrations (r equal to 0.75, p less than 0.001). In early gestation there was an attenuated plasma insulin response. Infants of gestationally diabetic mothers had increased umbilical plasma insulin levels — 23.3 ± 6.9 μU per milliliter (mean ± S.E.M.) — as compared to those of normal controls - 6.4 ± 1.3 μU per milliliter (mean ± S.E.M.) — even though the umbilical blood glucose levels in these two groups were similar. The data support the concept that hyperglycemia leads to hyperinsulinism in infants of diabetic mothers.
Results with salvage chemotherapy with high dose carboplatin + etoposide and peripheral blood stem cell transplant in male choriocarcinoma
Authors: M. Brames, G. Papiani, L. Einhorn
Journal: Journal of Clinical Oncology (2007)

5091 Background: Choriocarcinoma in males is seen usually as a small component of a mixed germ cell tumor. Pure choriocarcinoma accounts for a poor prognosis, usually presenting with high level of human chorionic gonadotropin (hCG &gt; 50,000 mIU/ml) and with pulmonary and non-pulmonary visceral metastases. Results with salvage chemotherapy in the past have been very poor with very few long-term survivors. Methods: Retrospective review of 184 germ cell patients treated with salvage high dose chemotherapy (HDCT) at Indiana University between 2–96 and 12–04 was presented (Proc Amer Soc Clin Oncol 24:228, abstract 4549, 2006). Thirteen of these patients had pure choriocarcinoma of the testis or choriocarcinoma syndrome (normal testes by palpation and ultrasound, normal serum alpha-fetoprotein, advanced hematogenous metastases, high level of hCG). Before HDCT, all the patients were treated with one or two regimens of standard cisplatin combination chemotherapy. HDCT regimen consisted of carboplatin 700 mg/m 2 and etoposide 750 mg/m 2 i.v. given for 3 consecutive days. A second course was given after hematologic recovery. Results: Toxicity was previously described (JCO 18:3346, 2000).The median survival was 19 months (range 5–90 months). Six patients (46%) are alive and continuously disease-free (cNED) with a median follow-up of 37 months (range 19–75). One additional patient is currently NED following subsequent chemotherapy and surgery. 3 of 7 patients with pure choriocarcinoma are cNED and 3 of 6 with choriocarcinoma syndrome are cNED. Six of 10 patients receiving HDCT as initial salvage therapy are cNED compared to 1 of 3 as third-line treatment. Conclusions: Salvage HDCT offers long-term disease-free survival and potential cure in patients with pure choriocarcinoma or choriocarcinoma syndrome that progressed after standard cisplatin combination chemotherapy. No significant financial relationships to disclose.
P13.20 * STEREOTACTIC RADIOTHERAPY FOR RECURRENT HIGH-GRADE GLIOMAS: A RETROSPECTIVE ANALYSIS
Authors: V. Pinzi, I. M. Milanesi, M. Marchetti, F. Dimeco, A. Franzini, P. Ferroli, A. Silvani, G. Finocchiaro, C. Orsi, l. Fariselli
Journal: Neuro-Oncology (2014)

PURPOSE: Numerous treatment options are available for recurrent high-grade gliomas (rHGG), including re-irradiation. Both fractionated stereotactic radiotherapy (FSRT) and radiosurgery (SRS) represent an optimal method to deliver high-dose radiotherapy to the small volume. Re-irradiation is often limited due to the dose-prescription and target volume. The primary end point of this retrospective study is to evaluate the efficacy of salvage SRS and FSRT in terms of overall survival; toxicity was analyzed as well. PATIENTS AND METHODS: Between 2004 and 2011, 128 patients (158 lesions) with recurrent high-grade gliomas (69% glioblastoma multiforme, WHO grade IV; 31% WHO grade III) were treated with CyberKnife stereotactic re-irradiation. FSRT was performed in 96 lesions with 3-5 fractions; SRS in 62 lesions. The median time from first irradiation and SRS re-irradiation was 12 months (range 6-171 months). RESULTS: A median survival time from the date of diagnosis was 32 months (95% CI, 25-43). Median survival time from the re-irradiation treatment was 11.5 months (95% CI, 10-12). Multivariate analysis confirmed that younger age and salvage surgery after SRS were associated with a significant improvement in survival. There have been 19 patients (15%) of G1-G2 acute toxicity (with headache, nausea, fatigue and alopecia) and 7 pts. (6%) of G3-G4 late toxicity (radiation-induced necrosis and neurological deterioration). CONCLUSIONS: Salvage re-irradiation with CyberKnife stereotactic radiotherapy for recurrent high-grade gliomas is safe and well tolerated. This strategy can be considered an effective treatment for recurrent HGG.
P397 HISTOLOGICAL REGRESSION IS NOT PREDICTED BY BIOCHEMICAL AND IMMUNOLOGICAL REMISSION IN AUTOIMMUNE HEPATITIS UNDER IMMUNOSUPPRESSION
Authors: E. Rodrigues-Pinto, H. Cardoso, P. Pereira, S. Lopes, M. Marques, R. Gonçalves, J.A. Sarmento, A.M. Horta e Vale, G. Macedo
Journal: Journal of Hepatology (2014)