tbuckley/cabot-search huggingface dataset:
Abstract 1870: Green tea polyphenol EGCG upregulates mir-210 expression in lung cancer cells by transiently stabilizing HIF1α
Authors: Hong Wang, Shengjie Bian, Chung S. Yang
Journal: Cancer Research (2011)

Abstract Epigallocatechin-3-gallate (EGCG) has been reported to affect many cellular regulatory pathways. This study aims to determine whether EGCG could target microRNA, one of the mechanisms for cells to achieve subtle change in multiple targets. We found that, in both human and mouse lung cancer cells in culture, EGCG specifically upregulated the expression of mir-210, a major microRNA regulated by HIF1α. Furthermore, we found that overexpression of mir-210 led to reduced cell proliferation rate and anchorage-independent growth as well as reduced sensitivity to EGCG. To explore the mechanisms of mir-210 regulation by EGCG, we demonstrated that the regulation was mediated through hypoxia-response element in mir-210 promoter. Consistently, the upregulation of mir-210 was found to be correlated with the transiently stabilized HIF1α in lung cancer cell lines after EGCG treatment. Such stabilization was further shown by the stabilization of HA-tagged HIF1α, but not the P402A/P564A mutated HIF1α, by EGCG, suggesting that EGCG targets the oxygen-dependent degradation (ODD) domain. Direct evidence was obtained by affinity binding assay showing that EGCG specifically binds HIF1α with a Kd=3.47 μM. This result implies that EGCG binding interferes with the hydroxylation of key Pro residues in the ODD domain, preventing HIF1α from the Pro hydroxylation-induced ubiquitination and subsequent proteosome-mediated degradation. In summary, our results demonstrate the elevation of mir-210 by EGCG and this is mediated by the stabilization of HIF1α. This event may contribute to the anti-cancer activity of EGCG (Supported by NIH grant CA 122474 and CA133021). 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 1870. doi:10.1158/1538-7445.AM2011-1870
Abstract LB-245: Loss of function of the TGFβRI receptor leads to the spontaneously regressing squamous carcinoma condition, multiple self-healing squamous epithelioma (Ferguson-Smith disease)
Authors: David R. Goudie, Mariella D'Alessandro, Barry Merriman, Hane Lee, Ildiko Szeverényi, Stuart Avery, Brian D. O'Connor, Stanley F. Nelson, Stephanie E. Coats, Arlene A. Stewart, Lesley Christie, Gabriella Pichert, Jean Friedel, Ian Hayes, Nigel Burrows, Sean Whittaker, Anne-Marie Gerdes, Sigurd Broesby-Olsen, Malcolm A. Ferguson-Smith, Chandra Verma, Declan P. Lunny, Bruno Reversade, E. Birgitte Lane
Journal: Cancer Research (2011)

Abstract A re-examination has been carried out of the region on chromosome 9 containing the locus responsible for Ferguson-Smith disease, or multiple self-healing squamous epithelioma (MSSE/FSD); this is a rare autosomal dominant inherited condition first identified in the west of Scotland, that presents with multiple squamous cell skin carcinomas which grow, invade locally and then spontaneously regress. Approach: A 4Mb locus on chromosome 9 was earlier identified by genetic mapping in a cluster of families. In this study a wider region encompassing 24Mb around this earlier identified locus was examined using high-throughput sequencing with exon capture, followed by Sanger sequencing. Result: This effort identified mutations in the TGFBR1 gene in 18 out of 22 families diagnosed as affected by MSSE/FSD. These include 11 different mutations. The tumours occur in sun-exposed areas of the skin, and loss-of-heterozygosity in tumours is frequently seen. The sequence variants disturb the function of the TGFβRI receptor such that although heterozygous carriers are asymptomatic during development, loss of the second (wild-type) allele ablates the receptor function and leads to local cancer susceptibility. Conclusions: The nature of the mutations sets the mechanism apart from that involved in Marfan syndrome-related disorders, in which developmental defects in vasculature are also caused by mutations in this gene. The involvement of TGFβ receptors in this condition is intriguing as TGFβ pathway effects are known to be biphasic and opposing at different stages of cancer development. 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 LB-245. doi:10.1158/1538-7445.AM2011-LB-245
Endoscopic placement of a fully covered self-expandable metallic stent to treat an arteriobiliary fistula
Authors: Hiroshi Kawakami, Munenori Okamoto, Masaki Kuwatani, Yoshimasa Kubota, Kazumichi Kawakubo, Yoko Abe, Shuhei Kawahata, Kimitoshi Kubo, Naoya Sakamoto
Journal: Endoscopy (2014)

Arteriobiliary fistula is an uncommon complication resulting from hepatic intra-arterial chemotherapy. We present a case of successful endoscopic intervention using a fully covered self-expandable metallic stent (SEMS) to treat an iatrogenic arteriobiliary fistula.
Patellar Metastasis From Lung Adenocarcinoma Revealed by FDG PET/CT
Authors: Ion Codreanu, Hongming Zhuang, Abass Alavi, Drew A Torigian
Journal: Clinical Nuclear Medicine (2012)

We report a case of a 57-year-old woman with lung adenocarcinoma, who presented with right knee pain, swelling, and erythema. The initial [18F]-2-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scan performed for staging purposes showed a right patellar metastasis, subsequently confirmed by pathology. After administration of systemic chemotherapy supplemented by local radiation therapy to the right patella, a follow-up FDG PET/CT scan revealed a grossly stable right patellar lesion. The patient underwent right patellectomy with reconstruction of the extensor mechanism. A subsequent FDG PET/CT scan showed postoperative changes, with no evidence of residual malignancy in the right knee region.
PTU-135 Elaar (the Enhanced Liverpool Abdominal Area Ratio): How To Use Cross-sectional Imaging To Assess Prognosis In End-stage Cirrhosis
Authors: SM Alam, C Farrell, I Patanwala, P Richardson, T Cross
Journal: Gut (2014)

<h3>Introduction</h3> Liver size may be important in prognostication in cirrhosis. The LAAR score has previously shown a relationship between liver size and survival but is hampered by subjectivity. The current study aimed to improve the existing score. <h3>Methods</h3> A retrospective-prospective cohort study was performed on patients with cirrhosis. The censor point used was date of patient death or liver transplant (LT) from CT date. Time points were measured from the date of the CT scan to censor point or last clinic appointment. The enhanced Liver<sup>pool</sup> to Abdomen Area Ratio (eLAAR) was derived using a software package (Carestream). eLAAR was calculated using the formula (Liver area (cm<sup>2</sup>)/Abdominal area (cm<sup>2</sup>) x 100. <h3>Results</h3> 101 patients were identified, 66% male, median age 52 (44–60 years). The LAAR score detected progression to death/LT in our cohort at 1 year (p = 0.02) and at 5 years (p = 0.03). The intra-class correlation coefficient between 2 operators was 0.94 (95% CI 0.89–0.97). Using an optimal eLAAR cut-off of 32 eLAAR could predict death at 1 and 5 years from diagnosis, p = 0.03 (OR 2.51(1.08–2.51) and p = 0.002 ()R 3.98 95% CI 1.5–10.4). Survival curves were constructed and the log rank test showed that eLAAR was able to predict death at 1 year (Log rank 5.3, p = 0.02) and 5 years (log-rank, p = 9.7, p = 0.002). <h3>Conclusion</h3> The eLAAR score offers a new paradigm to identify patients with poor prognostic criteria on cross-sectional imaging who may benefit from liver transplantation. <h3>Disclosure of Interest</h3> None Declared.
Abstract PD02-10: Radiation Induces Notch-Dependent <i>De Novo</i> Generation of Breast Cancer Stem Cells
Authors: C Lagadec, L Della Donna, E Vlashi, C Dekmezian, F. Pajonk
Journal: Cancer Research (2010)

Abstract Like in normal tissues, the self-renewal of cancer stem cells (CSCs) might be also under tight control of developmental pathway like the Notch, Wnt, Sonic Hedgehog or TGFβ pathways. The Notch pathway plays an important role in normal breast development, cell fate, and normal stem cell self-renewal, and its deregulation has been shown to play a role in cancer. Aberrant Notch signaling has been implicated in the development and progression of both preinvasive ductal carcinomas in situ and invasive. Interestingly, in breast cancer, the Notch pathway plays major role for CSCs maintenance. We previously published that BCSCs (Breast Cancer Stem Cells) are more resistant to radiation. Here we demonstrate a link between BCSCs radio-resistance and the Notch pathway. We show that irradiation of MCF-7 cells increases CSC numbers and that this correlates with an induction of Notch signaling proteins expression in a dose and time specific manner. Jagged 1 was quickly (1h) increased 28-fold after 2Gy, DLL1 was increased 15-fold after 3 to 6h of 2 and 4 Gy irradiation, and Notch 2 was increased 16-fold 6h after 2, 4, 6 or 8 Gy, while DLL3 was increased 10-fold after the highest doses (6 to 12 Gy). Inhibition of Notch signaling pathway by the γ-secretase inhibitor prevents enrichment for CSCs and reduces radiation-induced overexpression of Notch proteins. More interestingly, we demonstrated that radiation-induced Notch signaling contributes to the phenotype plasticity of BCSCs and their progeny. Therefore, ionizing radiation induces de novo generation of BCSCs from non-tumorigenic cells. Moreover, we also identified, by FACS analysis, an induction of polyploid CSCs. expressed a relatively higher level of Oct4 and Sox2 than the unirradiated non-CSCs (two key transcription factors involved in stemness maintenance). In summary, we provide evidence that radiation-induced Notch signaling contributes to the plasticity of the BCSC phenotype, thereby generating BCSCs de novo from non-tumorigenic cells. Our data suggest that stochastic as well hierarchical CSC models apply to breast cancer. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD02-10.
Correction: comparisons of Risks of Environmental Carcinogens
Authors: F. P. PERERA, P. BOFFETTA
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Correction: comparisons of Risks of Environmental Carcinogens Get access FREDERICA P. PERERA, FREDERICA P. PERERA Division of Environmental Sciences School of Public Health Columbia University60 Haven Ave, B-1 New York, NY 10032 Search for other works by this author on: Oxford Academic PubMed Google Scholar PAOLO BOFFETTA PAOLO BOFFETTA Division of Environmental Sciences School of Public Health Columbia University60 Haven Ave, B-1 New York, NY 10032 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 11, 7 June 1989, Page 880, https://doi.org/10.1093/jnci/81.11.880 Published: 07 June 1989
18F-FDG PET/CT of Primary Mediastinal Hepatoid Adenocarcinoma
Authors: Na Hu, Yanlin Tan, Jiadi Luo, Zhen Cheng, Yunhua Wang
Journal: Clinical Nuclear Medicine (2016)

Hepatoid adenocarcinoma is a rare extrahepatic tumor that shows clinicopathologic and morphologic similarities to hepatocellular carcinoma. An FDG PET/CT imaging of primary mediastinal hepatoid adenocarcinoma in a 43-year-old man who had an elevated serum alpha-fetoprotein level was reported in this case. The patient's mediastinal lesion had avid FDG uptake. Hepatoid adenocarcinoma should be considered among the differential diagnoses when an FDG-avid extrahepatic mass is seen in patients with increased alpha-fetoprotein.
Abstract 3380: Transient Tgfβ exposure causes persistent transdifferentiation in mouse mammary epithelial cells in vitro and in vivo
Authors: Karen A. Dunphy, Amy L. Roberts, Haoheng Yan, Luwei Tao, Mary J. Hagen, D Joseph Jerry
Journal: Cancer Research (2011)

Abstract Transforming growth factor beta (Tgfβ) is transiently increased during involution in the mammary gland following a pregnancy and may promote the risk of pregnancy associated breast cancer (PABC). While tgfβ inhibits growth of normal mammary epithelium and has a functional role in restoring the pre-pregnancy architecture of the mammary gland, this cytokine also has tumor promoter function because it promotes epithelial to mesenchymal transition (EMT) and initiates metastatic behavior in tumor cells. We hypothesize that transient Tgfβ exposure, to mimic involution, selects for cells that are susceptible to EMT and increases risk for PABC. We have found that short term 14 day treatment of CDβGeo cells, a mouse mammary epithelial cell line, with Tgfβ (5ng/ml) promotes EMT. These cells are persistently transdifferentiated (pTD) even after withdrawal of Tgfβ. In contrast to the parental CDβGeo cells, the pTD cells have decreased expression of E-cadherin (3-fold, p&amp;lt;0.05) and increased levels of N-cadherin (4-fold, p&amp;lt;0.05). The pTD cells also exhibited a striking increase in motility and invasion in Matrigel (invasion index &amp;gt;3-fold, p&amp;lt;0.01), but there was no difference in proliferation rates between CDβGeo cells and pTD cells. The pTD cells also were strongly tumorigenic when transplanted into cleared mammary fat pads (80% of pTD,TE50=43 days vs &amp;lt;10% of CDβGeo at 80days; p&amp;lt;0.01). Levels of Snail mRNA were also increased in pTD (2-fold;p&amp;lt;0.01) and in the tumors derived from the pTD transplants (&amp;gt;5-fold;p&amp;lt;0.01). In addition, expression of Tgfb2 mRNA was also increased (2.8-fold;p&amp;lt;0.05) in the pTD cells. These results demonstrate that transient exposure to Tgfβ causes persistent transdifferentation with increases in Snail and Tgfb2 expression in CDβGeo cells and suggest maintenance of transdifferentiation through an autocrine positive feedback loop. 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 3380. doi:10.1158/1538-7445.AM2011-3380
NIMG-26COMPARISON OF POST-GADOLINIUM 3D FAST SPIN ECHO IMAGES VERSUS REGISTERED AND SUBTRACTED MPRAGE IMAGES IN GLIOMA PATIENTS
Authors: Bradley Erickson, Timothy Kaufmann, Jay Agrawal, Panagiotis Korfiatis, Rickey Carter
Journal: Neuro-Oncology (2015)

BACKGROUND: Multiple 3D MRI methods can show contrast enhancement. One option is to acquire Magnetization-Prepared Rapid Gradient Echo (MPRAGE) images before and after gadolinium administration, register them, and subtract. Another option is to acquire only post-contrast images with high sensitivity to contrast, as with CUBE (GE Medical Systems) and SPACE (Siemens Medical Systems), grouped here as Fast Spin Echo (FSE). To our knowledge, no comparison of MPRAGE vs FSE has been performed. METHODS: IRB waived requirement for consent. For a period of 4 weeks (total 64 glioma patients), we prospectively collected MPRAGE images before and after contrast administration, as well as CUBE or SPACE images after gadolinium. Imaging was performed at 3T in all cases, on either Siemens or GE scanners. The pixel resolution was 1mm3. After contrast administration, a T2-weighted series was acquired and then FSE or MPRAGE followed by the other (order was randomly assigned). After acquisition, the MPRAGE images were registered, and then subtracted. All four images (FSE, Subtraction, MPRAGE Pre, and MPRAGE Post) were presented to 3 trained neuroradiologists. They were asked to provide a rating from 1-5 (1 = FSE definitely more apparent, 2 = probably, 3 = same, 4 = subtraction probably better, 5 = subtraction definitely more apparent). Signed rank tests, a non-parametric alternative to the paired t test, were used to test for differences between the two methods. RESULTS: FSE images better showed contrast enhancement for 2 of 3 individuals (p = 0.02, 0.004, 0.2) as well as the mean ratings over the 3 readers (p < 0.0006). In one case, all three readers agreed there was enhancement on FSE not seen on subtraction. In no case did all 3 readers agree the subtraction was better. In 30/64 cases, all three readers reported there was no difference in enhancement. CONCLUSIONS: 3D FSE images may be or more sensitive to contrast enhancement than registration/subtraction.
Successful endoscopic treatment using biological fibrin glue (Tissucol) for an enterocutaneous fistula occurring after cephalic duodenopancreatectomy
Authors: Ángeles Araujo-Míguez, Salvador Sobrino-Rodríguez, Ansel Avila-Carpio, Juan Bozada-García, Teófilo López-Ruíz, Juan Caballero-García, José Márquez-Galán
Journal: Endoscopy (2015)

An enterocutaneous fistula is an abnormal communication between the small or large bowel and the skin, which leads to external drainage of intestinal contents. It is an important issue in surgical practice, as most cases occur secondary to surgical complications and cause significant mortality and morbidity owing to septic complications [1] [2]. Postoperative fistulas account for 75 % – 85 % of all enterocutaneous fistulas. One-third of fistulas close spontaneously; the remainder require surgical intervention, with variable levels of success [1] [2]. Recently a few cases of endoscopic treatment with biological fibrin glue resulting in a good outcome have been reported [3] [4] [5].
ET-05 * INTRANASAL DELIVERY OF NEURAL STEM CELLS LOADED WITH ONCOLYTIC ADENOVIRUS EXTENDS SURVIVAL OF MICE WITH INTRACRANIAL GLIOMA
Authors: I. Balyasnikova, M. Dey, A. Tobias, D. Kanojia, G. Lee, Y. Han, L. Zhang, A. Ahmed, K. Aboody, M. Lesniak
Journal: Neuro-Oncology (2014)

Glioblastoma multiforme (GBM), the most common adult primary brain tumor, is in need of better and effective therapeutic options. In this study, we hypothesized that neural stem cells (NSCs) loaded with CRAd-S-pK7 oncolytic adenovirus (OV) can be successfully delivered via nasal application (IN) and will impart therapeutic efficacy in a murine model of human glioma. Recently, we demonstrated that radiation therapy increases the expression of CXCL12 in glioma xenografts, thus contributing to the enhanced migration of stem cells to the tumor site. We now show that hypoxic preconditioning of NSCs for 24h (1% oxygen) results in the two-fold increase of the CXCR4 expression on the surface of NSCs and doubles the rate of their migration towards glioma cells (p < 0.001) compared to untreated group. Hypoxic preconditioning of NSCs did not alter the OV replication as measured by E1A copy number. For in vivo studies, a patient derived GBM43 glioma cells were intracranially inoculated in nude mice. One week later, mice were treated with fractioned dose of irradiation at 2Gy for 5 days. NSCs (5x105) cultured under normoxic and hypoxic conditions were loaded with OV at 50 viral particles per cell, and IN inoculated 24h following the completion of the radiation. Kaplan-Meier survival analysis demonstrated that irradiation resulted in 44% improvement (p < 0.001) in median survival versus non-treated group. Survival of irradiated mice was not affected by either NSC's or OV-loaded NSCs, but was extended (p < 0.05) another 25% in the group of animals treated with OV-loaded NSCs cultured under hypoxic conditions. Thus, our data further validate the IN delivery as a novel route for the stem cell-based anti-glioma therapy, and suggest that modification of NSCs by enhancing their ability to migrate might significantly increase their therapeutic potential for IN delivery to target GBM.
SP0017 A stepped care approach towards hip and knee osteoarthritis in primary care
Authors: S. Bierma-Zeinstra
Journal: Annals of the Rheumatic Diseases (2012)

The management of hip and knee osteoarthritis has been reported to be non-optimal despite existing guidelines. To facilitate guideline implementation and improve utilization of non-surgical treatment options we developed an evidence-based, multidisciplinary, patient-centered, stepped care strategy. A Dutch multidisciplinary steering group developed the strategy in three subsequent stages: 1) consensus among steering group members based on existing national guidelines; 2) written consultation of representatives of patient organizations and professional associations involved in osteoarthritis care; 3) consensus of the final draft after discussion during a conference with representatives from the above mentioned disciplines. The final stepped care strategy provides guidance to the timing of non-surgical treatment modalities. It recommends that more advanced options should only be considered if options listed in previous steps failed to produce satisfactory results. The first step treatment options can be offered to all patients (education, life style advice, and acetaminophen). The second step (exercise therapy, dietary therapy, and non-steroidal anti-inflammatory drugs or other pain medication) and third step treatment options (multidisciplinary care, intra-articular injections, and transcutaneous electrical nerve stimulation) can be considered for people with persisting complaints. Based on a consensus procedure we developed a multidisciplinary, patient-centered, stepped care strategy for patients with hip or knee osteoarthritis, which provides a framework for health care providers and patients to discuss the optimal timing of the various treatment options. <h3>Disclosure of Interest</h3> None Declared
SAT0512 Comparison of Asdas ESR/ASDAS CRP with Basdai and Clinical Disease Activity in Enthesitis Related Arthritis: Table 1
Authors: M. Agarwal, S. Sawhney
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> BASDAI is a disease assessment tool that entirely depends upon patient/parent reporting and may not be able to capture the disease status when compared to clinical judgement. The cutoff range for high disease activity is 3.9 and those below this level though active do not fit into any group.Children often tend to overreport or under report and a more objective disease activity tool is warranted.ASDAS ESR and ASDAS CRP have been studied in adults but no such data in children from our country was available. Thus we intended to look for a more objective disease assessment tool for children with Enthesitis Related Arthritis and hence this pilot study was undertaken <h3>Objectives</h3> 1.) compare BASDAI with ASDAS ESR and ASDAS CRP 2.) To compare disease activity status clinically and with ASDAS ESR and ASDAS CRP <h3>Methods</h3> 200 consecutive BASDAI was collected on paper forms from all children diagnosed as Enthesitis related arthritis by ILAR classification who attended the pediatric rheumatology clinic.Patient global score and physician global scores were given and ASDAS ESR,ASDAS CRP were calculated using the ASDAS calculator available online <h3>Results</h3> 200 BASDAI forms were collected from 110 children (87 boys). At disease onset, 10 children had only axial involvement and 44 children had only peripheral disease whereas 53 had both axial and peripheral involvement. Only 7.5% were more than 3.9 indicating very high disease activity warranting a biologic agent. ASDAS ESR was able to pick up all those with high disease activity on BASDAI. A high level of agreement was found in ADAS ESR and disease status clinically. ASDAS CRP picked up all with high disease activity on BASDAI <h3>Conclusions</h3> ASDAS ESR and ASDAS CRP were both able to correlate well with clinical disease activity.CRP rises earlieras compared to ESR and falls more rapidly and is mirrored with more children with clinically inactive disease with low disease activity by ASDAS CRP as compared to ASDAS ESR. Limitations: Change of ASDAS ESR and ASDAS CRP over time has not been studied <h3>Disclosure of Interest</h3> None declared