tbuckley/cabot-search huggingface dataset:
Abstract 3030: Hypoxia induces BACH1 expression regulating colon cancer metastasis
Authors: Jin Young Lee, Yeong Nang Jo, Jin-Ah Kim, Chang Woo Lee, Ok-Jun Lee, Sang-Bae Han, Song-Kyu Park, Jong Soon Kang, Jieun Yun
Journal: Cancer Research (2012)

Abstract BACH1 (BTB and CNC homology 1) is a basic region-leucine zipper (bZip) transcription factor that binds to MAREs (Maf recognition elements) and acts as a repressor of genes that regulate the oxidative stress response. It has been reported that BACH1 is a novel let-7 target and regulates breast cancer metastasis. Here we show that hypoxia induces BACH1 expression by regulating BACH1 promoter activity. In a mouse xenograft model, BACH1 depletion reduces the primary tumor growth of HCT-116 colorectal cancer cells. In addition, knockdown of BACH1 significantly decreases the invasive efficiency of colorectal cancer cells. Finally, we confirm that BACH1 expression is high in the patient samples of colorectal cancer and metastasis, unlike normal colon tissues. These results suggest BACH1 as a novel target for cancer therapeutic strategy. 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 3030. doi:1538-7445.AM2012-3030
Abstract 4225: Expression of NANOG in a prostate cancer cell line increases CD24 expression and enhances cell invasion
Authors: Macie Fowler, Jonathan Glass, Hong Yin
Journal: Cancer Research (2010)

Abstract The transcription factor NANOG is critical for the maintenance of embryonic stem cell properties including self-renewal and pluripotency. NANOG performs these functions by regulating the expression of genes required for the preservation of the stem cell phenotype. Introduction of NANOG and other embryonic stem cell genes has successfully established disease-specific induced pluripotent stem cells in several types of human cancers. Although the expression of NANOG has been documented in cancer cells, the function of NANOG in cancer has not been extensively investigated. We hypothesized that NANOG plays a role in prostate cancer cell biology based on our observation of NANOG protein expression in prostate cancer cell lines. To test this hypothesis, we transduced the PC3 prostate cancer cell line with a lentivirus capable of directing the expression of NANOG. A stable cell line containing the NANOG expression cassette was established by selection with puromycin, and expression of NANOG protein was verified by Western blot analysis. Analysis of stem cell surface markers by flow cytometry in the PC3-NANOG cells and PC3 cells transduced with empty virus revealed an increase in the percentage of CD24 positive cells in the PC3-NANOG sample as compared with the control. In addition, the density of CD24 per cell appeared to increase. This increase in CD24 expression was confirmed by Western blot analysis. In multiple cancers expression of CD24, a mucin-like adhesion protein, correlates with invasion and metastatic potential. Therefore, we conducted an invasion assay to assess the ability of PC3-NANOG cells to invade through a matrix assaying invasion by migration of cells from one chamber of a bicameral chamber through a porous membrane. The results showed that PC3-NANOG cells exhibited a 30-40% increase in invasion as compared to the control cells. (p&amp;lt;0.001). These results suggest that expression of NANOG in a prostate cancer cell line contributes to increased invasive capacity, possibly through enhanced expression of CD24. Therefore, NANOG could be a potential mediator of prostate cancer cell invasion and maneuvers to decrease NANOG expression could be a new therapeutic target for treatment of prostate cancer. 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 4225.
Case 3-1998
Authors: Ellen E. Sheets, R. Neal Smith
Journal: New England Journal of Medicine (1998)

Presentation of CaseA 31-year-old woman was admitted to the hospital because of fever, cough, questionable pneumonia of the left lower lobe with a left pleural effusion, and ascites.The patient had been well until one month earlier, when she began to have a cough with fever, sweats, and chills. Twelve days before admission to this hospital, she entered another hospital because of pneumonia of the left lower lobe that did not improve after a three-day course of azithromycin.The temperature was 38.4°C, the pulse was 118, and the blood pressure was 100/70 mm Hg.On physical examination, the patient . . .
THU0152 Incidence of Opportunistic Infections in Rheumatoid Arthritis Treated with Biological Agents
Authors: A. Gόmez, Z. Rosales Rosado, R. Peña, M.E. Toledano, L. Arietti, E. Pato, L. Leόn, M. Blanco, J.Ά. Jover, L. Rodríguez, L. Abásolo
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> With the expanding use of Biological Agents (BA), in particular TNF inhibitors, opportunistic infections (OI) are a major concern in Rheumatology. <h3>Objectives</h3> a) To describe the incidence of OI global and by periods in Rheumatoid Arthritis (RA). b) To compare the risk of OI by BA. <h3>Methods</h3> We performed a retrospective longitudinal observational study from 1/1/2000 to 23/11/2013. We included subjects followed up in our outpatient clinic, diagnosed with RA according to ACR criteria 87, whom started treatment with a BA [etanercept (ETN), golimumab (GOLI), certolizumab (CTZ), infliximab (IFX), adalimumab (ADA), rituximab (RTX), abatacept (ABA), or tozilizumab (TZL)]. Our primary end point was OI that involved the suspension of the BA. We consider OI when there was a positive culture (for Candida, Aspergillus or Herpes) or compatible symptoms that responded to specific treatment. We also collected secondary variables: sociodemographic (age, sex); clinical (disease duration, types of BA, hospital admission, previous BA). Statistical analysis: We used survival techniques to estimate the incidence of global OI and OI by periods (1st: 98-2002, 2nd:2002-2007, 3rd: 2007-2013), expressed per 1000 patient-year [CI 95%]. The exposure time was defined from the start date of each BA to suspension, loss of follow up or end of study (23/11/2013). We performed Cox regression models (adjusted by age, duration of RA, sex, calendar time and prior BA) to compare the risk of OI between each BA. <h3>Results</h3> 405 RA patients were included in the study, they started 744 different courses of BA treatment, with a total follow-up of 1,612 patient-years. Of these, 81% were women with a mean age at diagnosis of 52.5±13 years. The most frequently used drug was ADA (32%), followed by ETN (25%), IFX (21%) and RTX (14%). There were 16 OI (6 Candidas, 2 Aspergillus and 8 Herpes Zoster), 40% required hospitalization and two died of disseminated candidiasis. The incidence of OI was 9.9 [6.1-16.2], and tended to increase over time (1st: 5.9 [1.5 to 23.9]; 2nd: 7.7 [2.9 to 20, 6]; and 3rd: 13.1 [7.1 to 24.3]). We only registered OI cases in anti-TNF and RTX, which is the drug with higher incidence (n=3, I: 20.1 [6.4 to 62.4]). We found no statistically significant association between RTX compared with other BA and the development of OI <h3>Conclusions</h3> The incidence of OI and its evolution over time in real life conditions is described. It seems that OI tend to increase over time and we had two cases with fatal outcome. Doctors using BA should be concerned about this problem and be aware of the optimal methods for the detection and management of OI. We did not find statistical differences in the rate of OI between BA. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4509
SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS) ASSOCIATED WITH GLIOMA SURVIVAL
Authors: M. Wrensch, K. M. Walsh, I. V. Smirnov, T. Rice, H. M. Hansen, A. M. Molinaro, L. S. McCoy, P. M. Bracci, B. S. Cabriga, A. Perry, R. Marshall, M. Pekmezci, S. Zheng, J. L. Wiemels, T. Tihan, M. S. Berger, S. M. Chang, M. D. Prados, J. K. Wiencke, P. Decker, M. Kosel, J. Eckel-Passow, A. Caron, T. Kollmeyer, B. O'Neill, C. Giannini, J. Buckner, D. Lachance, R. Jenkins
Journal: Neuro-Oncology (2014)

BACKGROUND: In 2012, using a genome-wide association study (GWAS) of UCSF Adult Glioma Study patients and replication in patients from the Mayo Clinic, TCGA and GliomaSE, we showed that a SNP in SSBP2 on chromosome 5 was associated with survival of glioblastoma (GBM) patients who received standard of care (SOC). Since then we have examined 41 SNPs that were potentially associated with survival after glioma diagnosis based on our preliminary results or published results of others. METHODS: The data set consisted of 401 patients with grade 2 or grade 3 astrocytic, oligodendroglial, or mixed oligoastrocytic tumors and 339 GBM patients not included in the previous GWAS. RESULTS: The SSBP2 minor allele was again associated with poorer survival among GBM patients who received SOC, but interestingly with improved survival among Grade 2 and Grade 3 patients. SNPs in another region of chromosome 5 were associated with GBM survival irrespective of whether or not the patients had SOC. Several other SNPs were significantly (p < 0.05) associated with survival of GBM or lower grade glioma. The results are currently being replicated in a similar sized group of patients from the Mayo Clinic. CONCLUSIONS: Inherited germline variation may influence glioma survival. SECONDARY CATEGORY: n/a.
THU0161 Increase in Circulating TH17 Cells during Anti-TNF Therapy in Rheumatoid Arthritis Patients is Associated with Improvement in Joint Inflammation
Authors: D. Hull, S. Abraham, R.O. Williams, P.C. Taylor
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Anti-TNFα agents have revolutionised treatment of rheumatoid arthritis (RA), although a significant proportion of patients respond inadequately. Studies in murine and human arthritis have paradoxically shown that anti-TNF treatment can increase circulating Th17 cells but the relationship of these changes to treatment responses remains unclear. <h3>Objectives</h3> To investigate immune correlates of anti-TNF treatment response or failure in RA patients we conducted a longitudinal study using serial clinical, ultrasound and T cells immunological assessments. <h3>Methods</h3> 25 RA patients naïve to biological therapy were followed at 4 predetermined protocol visits during the first 12 weeks of anti-TNF treatment (etanercept or adalimumab). Improvement in Disease Activity Score of 28 joints (DAS28) defined treatment responders (n=16) and non-responders (n=9). Changes in synovial thickening and vascularity of 10 metacarpophalangeal joints were quantitatively assessed by 2D high frequency grey scale and power Doppler ultrasound (PDUS) using a digitalised pixel counter. Changes in the frequency of circulating Th17 cells during treatment were evaluated by IL17 ELISpot assay and Flow Cytometry (FACS) of PBMCs. <h3>Results</h3> ELISpot analysis demonstrated a significant increase in circulating IL17-producing cells 12 weeks after anti-TNFα initiation (baseline mean ± SD 466±277 vs 12 weeks mean ± SD 759±510 spSFC/10<sup>6</sup>, p=0.003). FACS analysis confirmed a significant increase in CD4+IL17+ cells at treatment week 12 (baseline mean ± SD 0.7±0.5% vs 12 weeks mean ± SD 1.1±0.5%; p=0.01). This increase in circulating Th17 cells during anti-TNFα treatment was observed in patients treated with different types of anti-TNFα agents, suggesting this may be a class effect. The increase in circulating Th17 cells during treatment correlated significantly with reduction in synovial vascularity (Spearman rank r= -0.68, p=0.007) and synovial thickening (Spearman rank r= -0.39; p=0.04) as determined by PDUS. Higher numbers of circulating Th17 cells at baseline were associated with poorer anti-TNFα treatment response as defined by ultrasonographic measures. <h3>Conclusions</h3> This is the first study to link changes in circulating Th17 cells evaluated by cellular assays with resolution of ultrasonographic features of synovitis during anti-TNF treatment. The findings may reflect redistribution of Th17 cells from inflamed joints during treatment or that TNFa may play a role in the regulation of Th17 cell production, but these two hypotheses are not mutually exclusive. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1030
Transparency and the European Medicines Agency — Sharing of Clinical Trial Data
Authors: Sergio Bonini, Hans-Georg Eichler, Noël Wathion, Guido Rasi
Journal: New England Journal of Medicine (2014)

Guided by public health interests, the European Medicines Agency has set new standards for clinical trial data transparency by adopting a 2010 policy on access to documents and a 2014 policy on publication of clinical data for medicinal products for human use.
Abstract 539: Endosialin (TEM1) is a tumor stroma marker and receptor for the metastasis-related Mac-2 binding protein
Authors: Matthias Wieland, Renate Becker, Sivanandam Vijayshankar, Carolin Mogler, Eva Besemfelder, Sven Christian, Hellmut G. Augustin
Journal: Cancer Research (2010)

Abstract Endosialin is a heavily sialylated C-type lectin. It is a single transmembrane molecule that was identified by two independent studies as an angiogenic endothelial specific marker. However, recent high resolution confocal expression studies by our and other laboratories have revealed that Endosialin is not expressed by endothelial cells but instead by angiogenic blood vessel associated pericytes. Detailed tissue array-based expression profiling validated Endosialin as an oncofetal gene product of the mesenchymal lineage that is hardly detectable in normal tissues but abundantly expressed by tumor vessel-associated pericytes and tumor stromal fibroblasts (myofibroblasts). As such, Endosialin was not just identified as a marker of activated pericytes but based on its exclusive tumor-associated expression also as a novel therapeutic tumor stroma target. Cytokine induction experiments identified Endosialin as a major downstream target of TGFß stimulation. Cellular siRNA-based loss-of-function experiments unravelled a role of Endosialin in the regulation of mesenchymal cell adhesion, migration and proliferation. These findings prompted experiments aimed at identifying the extracellular ligand of Endosialin. Using Endosialin-Fc as an affinity probe, the metastasis associated molecule Mac-2BP/90K was identified as high affinity extracellular Endosialin ligand. As Endosialin, Mac-2BP/90K displays an exclusive tumor progression associated expression pattern. However, in contrast to the stromal expression of Endosialin, Mac-2BP/90K is strictly expressed by the tumor cell compartment. The mutually exclusive expression pattern suggests a repulsive interaction between Endosialin and Mac-2BP/90K which was confirmed in cellular experiments. Ongoing experiments are aimed at mechanistically studying the role of the Endosialin - Mac-2BP/90K interaction in controlling the crosstalk between the tumor cell and the stromal cell compartments during tumor progression and metastasis. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 539.
Evaluation of the Predictive Value of IGF-IRa, IGF-IRb, UPA, and PAI-1 in Patients with Advanced Breast Cancer (ABC) Treated with Trastuzumab.
Authors: I. Kostopoulos, G. Karayannopoulou, M. Bobos, D. Skarlos, E. Briassoulis, A. Koutras, D. Pectasides, H. Linardou, E. Razis, F. Matsiakou, K. Kalogeras, G. Fountzilas
Journal: Cancer Research (2009)

Abstract Background: It has been shown that the HER2 and uPA/PAI-1 pathways independently affect the aggressive behavior of breast tumors. While HER2 positive patients have been shown to respond to trastuzumab, the role of uPA and PAI-1 in patients with advanced breast cancer (ABC) treated with trastuzumab is unclear, while the IGF-IR pathway appears to mediate resistance to trastuzumab.Material and Methods: Formalin-fixed paraffin-embedded tumor tissue samples were retrospectively collected from 138 patients with ABC treated with trastuzumab in the first-line. Clinical information was retrieved from medical records. The median age of the patients was 55 years, with 31% being premenopausal. HER2, IGF-IRa, IGF-IRb, uPA, PAI-1, Ki-67, ER, and PgR were assessed centrally by immunohistochemistry (IHC), while HER2 was also assessed centrally by FISH. All stains were examined by 2 independent pathologists, using the Allred 8-unit system for IGF-IRa and IGF-IRb, a combination of a proportion score from 0 to 5 and an intensity score on a scale of 0 to 3 (none, weak, moderate, strong). uPA protein expression was considered positive if &amp;gt;75% of the cells showed intense staining, with PAI-1 deemed positive when &amp;gt;6% of the cells showed mild staining. PFS and survival from the initiation of trastuzumab were estimated by the Kaplan-Meier method and compared using the log-rank test.Results: Trastuzumab alone or in combination with chemotherapy and/or hormonal therapy was given as first-line treatment in all patients. HER2 gene amplification was confirmed in 89 cases, while in 49 patients HER2 was found to be non-amplified (HER2 negative patients). As expected, survival of HER2 positive patients was found to be significantly longer (50.7 months vs. 30.5 months, p&amp;lt;0.0001), with no significant differences found in PFS (14.0 months vs. 9.2 months, p=0.124). IGF-IRa, IGF-IRb, uPA, or PAI-1 positive patients were not found to have significantly different PFS or survival in either HER2 positive or negative patients.Discussion: Protein expression of IGF-IRa, IGF-IRb, uPA, or PAI-1 assessed by IHC was not found to be associated with significantly different survival in patients with advanced breast cancer treated with trastuzumab in the current analysis. Studies are ongoing to include patients receiving second-line treatment with trastuzumab and evaluation of PI3K mutations. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2036.
Presence of Fragmented QRS and Its Relationship with Cardiac Functions in Patients with Obstructive Sleep Apnea
Authors: Adem Adar, Abdulkadir Kırış, Yılmaz Bülbül, Hüseyin Bektaş, Sercan Okutucu, Murat Acat, Hasan Casim, Hakan Orhan Elönü, Tayyar Gökdeniz
Journal: Journal of the American College of Cardiology (2013)
Successful endoscopic removal of a cocaine capsule in the stomach: should it be considered a safe therapeutic option?
Authors: Rosa Coelho, Branca Orfão, Guilherme Macedo
Journal: Endoscopy (2014)

Body packers, also called "swallowers" or "mules", are people who swallow amounts of wrapped drugs [1] [2]. In those who are asymptomatic, conservative treatment should be considered, so allowing spontaneous passage of the packets [1] [3]. When this fails, surgery is usually the first option [4] [5] [6]. However, as suggested by a review article on internal concealment of illicit drugs [3], endoscopic removal can be a therapeutic option and is a reasonable alternative to surgery when only one packet has failed to pass beyond the pylorus. There are only three cases reported in the literature of the successful endoscopic extraction of cocaine packets from the upper digestive tract [7] [8] [9].
PROFICIENCY PERFORMANCE BENCHMARKS FOR REMOVAL OF SIMULATED BRAIN TUMORS USING NEUROTOUCH
Authors: R. Del Maestro, G. Al Zhrani, H. Azarnoush, A. Winkler-Schwartz, F. Alotaibi, S. P. Lajoie
Journal: Neuro-Oncology (2014)

BACKGROUND: Objective assessment of neurosurgical technical skills involved in the resection of cerebral tumors in operative environments is complex. Educators emphasize the need to develop and use objective and meaningful assessment tools that are reliable and valid for assessing trainees' progress in acquiring surgical skills. Novel technologies, such as virtual-reality simulation, have the potential to play important roles in the training of neurosurgeons. The purpose of this study was to develop benchmarks for a newly proposed set of objective measures (metrics) of neurosurgical technical skills performance during simulated brain tumor resection using a new virtual reality simulator (NeuroTouch). METHODS: A total of 31 participants were recruited including 16 ‘experts’ (neurosurgery staff) and 15 neurosurgery residents (‘novices’, 7 junior and 8 senior). Each participant performed 18 simulated brain tumor resections utilizing the NeuroTouch platform. The metrics for assessing surgical performance were computed using the NeuroTouch simulator and consisted of 1) Safety metrics including, volume of surrounding normal tissue removed, maximum force applied and sum of forces utilized during tumor resection 2) Quality of Operation metric which involved the percentage of tumor removed and 3) Efficiency metrics including duration for task completion, instrument path lengths and pedal activation frequency. RESULTS: The results demonstrated that ‘expert’ neurosurgeons (neurosurgery staff) resected less surrounding simulated normal brain tissue and less tumor tissue then residents. This data is consistent with the concept that ‘experts’ focused more on safety of the surgical procedure compared to novices. By analyzing experts' neurosurgical technical skills performance on these different metrics we were able to establish benchmarks for goal proficiency-based training of neurosurgery residents. CONCLUSIONS: Examining ‘expert’ neurosurgical performance in simulated settings such as NeuroTouch provides researchers with novel metrics for assessment of technical skills and development of proficiency based benchmarks. Identification of expert proficiency can led to improvements in resident training and assessment SECONDARY CATEGORY: n/a.