tbuckley/cabot-search huggingface dataset:
CB-03 * IDENTIFICATION AND CHARACTERISATION OF MicroRNAs INVOLVED IN GLIOBLASTOMA CELL PROLIFERATION AND SURVIVAL USING HIGH-THROUGHPUT SCREENING
Authors: M. Boissinot, J. Hayes, M. Adams, J. Higgins, D. Tomlinson, S. E. Lawler, S. C. Short
Journal: Neuro-Oncology (2014)

INTRODUCTION MicroRNAs, single-stranded non-coding RNAs that function by reducing translation or causing degradation of target mRNAs, have been shown to play roles in multiple hallmarks of GBM, suggesting they may be of therapeutic importance. METHODS: The miRIDIAN mimic library (Dharmacon) that encompasses all human microRNAs annotated in miRBase v16.0 was used with a high-throughput imaging platform (Operetta) to identify microRNAs with potent effects on GBM cell proliferation and survival. Screens were performed in duplicate on U251 (adult) and KNS42 (paediatric) GBM cell lines. Cell number (nuclei count) was assessed 72h post-transfection and expressed as a z-score for each microRNA. MicroRNAs were considered significant candidates if their mean z-score was below zero and if it differed from that of the negative control by at least two standard deviations. Validation included RTqPCR, imaging and flow cytometry based assays. RESULTS: The functional screens resulted in approximately 100 candidates per cell line with 70% overlap between them. Based on available knowledge and potential relevance for GBM therapy, seven initial microRNAs candidates were chosen for further validation in a panel of four adult and two paediatric GBM cell lines: miR-34a-5p, miR-34b-5p, miR-34c-5p, miR-449a-5p, miR-449b-5p which all share a common seed sequence; miR-340-5p and miR-X. Of these candidates miR-X was identified as having the most potent, robust effects. MiR-X consistently caused a G2M cell cycle arrest followed by apoptosis in all cell lines and has predicted targets involved in the induction of the cytoskeleton rearrangement and non-canonical Wnt pathways following the G2M phase transition. This phenotype was specific to mimic-miR-X transfected cells. CONCLUSION: We have identified a novel potent pro-apoptotic microRNA in GBM that may be relevant for therapy. Work is ongoing to characterise the mechanism responsible for this effect and test for efficacy in vivo.
ET-52 * SIMULTANEOUS BRAIN DELIVERY OF A THREE ANTI-CANCER DRUG COMBINATION VIA A PEPTIDE CARRIER-MEDIATED INTRAVENOUS INJECTION OF THE THREE-DRUG COCKTAIL
Authors: G. Sarkar, G. Curran, R. Jenkins
Journal: Neuro-Oncology (2014)

BACKGROUND: Combinations of anti-cancer medications often yield better outcome than a single medication in the treatment of patients with cancer including patients with brain cancer. However, limitations imposed by the blood-brain barrier (BBB) create serious challenge to deliver even a single drug to the brain, let alone a combination of drugs. We have developed a peptide carrier K16ApoE, which apparently creates transient opening of the BBB. We investigated the ability of the carrier peptide to deliver a three-drug combination (cetuximab, cisplatin and methotrexate) to the brain injected via intravenous route. METHODS: Brain delivery of the drugs was achieved either by separate or combined administration of K16ApoE and a given drug(s) through femoral vein injection. A modification of the method comprised injection of K16ApoE pre-mixed with cetuximab, followed by injection of a drug. Brain uptake of cetuximab was assessed by micro single photon electron computed tomography (microSPECT). Quantification of brain uptake of cisplatin and methotrexate were achieved by atomic absorption spectrometry and LC-MS/MS, respectively. RESULTS: Experiments designed to deliver cetuximab, cisplatin and methotrexate separately show brain-uptake of the drugs was ∼3-fold, ∼40-fold and ∼51-fold greater with K16ApoE than without, amounting to brain uptake of ∼0.5% for cetuximab and ∼1.5% each for cisplatin and methotrexate, respectively, of the injected dose. Experiments designed to deliver cetuximab, cisplatin and methotrexate simultaneously (in a mixture) produced brain uptake of the three drugs at ∼3-fold, ∼18-fold and ∼41-fold greater with K16ApoE than without for cetuximab, cisplatin and methotrexate, respectively, which amounted to brain uptake of∼ 0.5% for cetuximab, ∼0.7% for cisplatin and ∼ 0.5% for methotrexate. SIGNIFICANCE: The results suggest that multiple anti-cancer agents can be simultaneously delivered to the brain via the synthetic carrier peptide K16ApoE. Thus, the method offers a novel therapeutic avenue for intervention against brain cancer.
THU0038 Histologic features of osteochondral junction in joint disorders
Authors: O. Addimanda, B. Pavloska, L. Pulsatelli, G. Lisignoli, A. Facchini, R. Meliconi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Osteochondral junction (OCJ) is a crucial region in OA onset and progression. Characteristic feature of OCJ are: calcified cartilage, tidemark and possible vascular invasion. New blood vessels from the subchondral bone may invade calcified cartilage and even breach the tidemark. (1). <h3>Objectives</h3> To investigate the histologic features of cartilage and OCJ in Osteoarthritis (OA), Inflammatory Arhritis (IA) and Post-Traumatic Cases (PTC). <h3>Methods</h3> Osteochondral biopsies were obtained from the surgical specimens of 60 patients with OA, 11 patients with IA and 23 PTC who underwent joint replacement (knee, hip, shoulder) because of arthritis or traumatic fractures. Biopsies (3 samples per patient) were processed as previously described (2) and paraffin embedded. 5 μm slides were cut and stained with Ematossilin-Eosin and with Safranin-O and evaluated utilizing Mankin and Chambers scores, in order to quantify cartilage damage. Tidemark duplication and cartilage-subchondral vascular invasion (numbers of vessels crossing osteochondral junctions) were evaluated. Demographic features (sex, age and BMI) from all patients were recorded. <h3>Results</h3> Arthritis patients were older and with a slightly higher BMI than PTC [age (mean ± sd) =73.6±7.2 vs 71.9±12.0, p=0.04; BMI (mean ± sd) =29.5±4.1 vs 28.8±4.6, p=0.02]. We found a significantly higher total Mankin score in OA and IA patients compared to PTC [Total Mankin score OA + IA (mean ± sd) =7.24±2.96 vs PTC 4.120±3.25, p = &lt;0.0005] without significant differences between OA and IA cases [OA Total Mankin score (mean ± sd) =6.58±3.01 vs IA Total Mankin score (mean ± sd) 7.90±2.92, p=0.89]. Same results were obtained utilysing Chambers scores. Tidemark duplication was found in similar percentages in all three groups (OA =52%, RA =44%, PTC =33%, p=0.61 – Kruskall-Wallis test). The number of OCJ invading vessels was higher in arthritis (OA and IA) samples compared to PTC ones (p=0.0079).A correlation between Mankin score and the number of vessels invading calcified cartilage was found only in IA patients (p=0.0008), but not in OA and PTC samples. <h3>Conclusions</h3> Cartilage damage, vessel OCJ invasion and tidemark duplication is similar in OA and IA. Therefore our study questions the OA specificity of tidemark duplication and vascular invasion of calcified cartilage. <h3>References</h3> Fransès R.E, McWilliams D.F, Mapp P.I, Walsh D.A. Osteochondral angiogenesis and increased protease inhibitor expression in OA. Osteoarthritis and Cartilage 2010;18:563–571. Lisignoli G, Toneguzzi S, Grassi F, Piacentini A, Tschon M, Cristino S, Gualtieri G, Facchini A. Different chemokines are espresse in human arthritic bone biopsies: IFN-gamma and IL-6 differently modulate IL-8, MCP-1 and rantes production by arthritic osteoblasts. Cytokine 2002;20:231-8. <h3>Disclosure of Interest</h3> None Declared
OP0074 A Concentration-Effect Curve of Adalimumab in Patients with Psoriatic Arthritis
Authors: E. Vogelzang, E. Kneepkens, M. Nurmohamed, A. van Kuijk, T. Rispens, G. Wolbink, C. Krieckaert
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> In rheumatoid arthritis the concentration-effect relationship of adalimumab has been investigated.[1] However, in psoriatic arthritis (PsA) there is a lack of knowledge about the pharmacodynamics and pharmacokinetics of adalimumab. <h3>Objectives</h3> To investigate the relationship between serum adalimumab trough concentrations and clinical response in PsA patients after 28 weeks of treatment, using a concentration-effect curve. <h3>Methods</h3> In this prospective cohort study 103 consecutive patients diagnosed with PsA were included and treated with 40 mg adalimumab subcutaneously every other week. Adalimumab concentrations at 28 weeks of treatment were measured in serum trough samples, using an enzyme linked immunosorbent assay (ELISA). Clinical response was defined as a change in disease activity score in 28 joints (ΔDAS28) between baseline and week 28. All patients were sorted from low to high adalimumab concentration (mg/L). Each dot represents 10 patients (the last dot represents 13 patients) and their mean adalimumab trough concentration and mean ΔDAS28. <h3>Results</h3> At 28 weeks of treatment serum trough concentrations ranged from 0.0 to 18.8 mg/L, with a mean of 7.2 mg/L. Concentrations of approximately 1.0 mg/L already showed reasonable efficacy. Adalimumab concentrations of 5-8 mg/L appear most optimal. (see figure 1) Concentrations above 8 mg/L appear to have no additional benefit. In 48 (47%) patients adalimumab concentrations exceeded 8 mg/L. Furthermore 36 (35%) patients had adalimumab concentration below 5 mg/L. <h3>Conclusions</h3> Adalimumab concentrations of 5-8 mg/L appear necessary for achieving the most optimal clinical benefit. A substantial group of PsA patients that uses adalimumab are not able to profit from this optimal clinical benefit. This study, in patients with PsA, confirms the results that have been found in RA patients. <h3>References</h3> Pouw MF et al. Key findings towards optimising adalimumab treatment: the concentration-effect curve. Ann Rheum Dis. 2013 [Epub ahead of print]. <h3>Disclosure of Interest</h3> E. Vogelzang: None declared, E. Kneepkens: None declared, M. Nurmohamed: None declared, A. van Kuijk: None declared, T. Rispens Speakers bureau: Pfizer and Abbvie, G. Wolbink Grant/research support: Pfizer, Speakers bureau: Pfizer and Amgen, C. Krieckaert Speakers bureau: Pfizer and Abbvie <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1863
Abstract P5-01-10: Tumor Optic Properties Measured Using Diffuse Optic Spectroscopy Imaging Correlate with Proliferation and Glucose Metabolism in Breast Cancer Patients
Authors: S Ueda, AE Cerussi, PM Carpenter, D Roblyer, A Durkin, D Hsiang, RS Mehta, JA Butler, BJ. Tromberg
Journal: Cancer Research (2010)

Abstract (Background) Diffuse Optic Spectroscopy Imaging (DOSI) is non-invasive imaging technology that employs near-infrared (NIR) light to quantitatively characterize the hemodynamic and metabolic properties of breast cancer tumors. (Methods) We utilized DOSI to measure baseline tumor concentrations of oxy-hemoglobin (ctO2Hb), deoxy-hemoglobin (ctHHb), total hemoglobin (ctTHb), oxygen saturation (stO2), as well as water and lipid content of tumors from sixteen patients with primary breast cancer prior to neoadjuvant chemotherapy. Core-needle biopsy specimens were also collected from these patients and analyzed for Ki67, Glut-1, and Fatty acid synthese (FAS), biomarkers of cancer proliferation, glucose metabolism and fatty acid metabolism, respectively. These optic and biological biomarkers were statistically compared to each other and to overall therapy response. (Results) Ki67 score was positively correlated with baseline levels of ctO2Hb (µM) (r = 0.51, p = 0.04), ctTHb (µM) (r = 0.51, p = 0.05), and stO2 (%) (r = 0.57, p = 0.02), and negatively correlated with lipid content (%) (r = -0.52, p = 0.04). Tumors with positive Glut-1 status (n=8) showed significantly higher baseline levels of ctO2Hb (26.2±12.5 v.s 19.9±10.1, p = 0.04), ctTHb (41±13.3 v.s 27.5±11.7, p = 0.05), and stO2 (81.1±6.6 v.s 70.2±9.9, p = 0.02) and lower baseline levels of lipid (49±17.1 v.s 66.2±10.4, p = 0.03) compared to those with negative Glut-1 status (n = 8). There were no correlation between FAS and the optic properties. Five (31.3%) of 16 tumors achieved pathologic complete response (pCR) after completion of chemotherapy followed by surgery. Tumors with pCR showed higher stO2, higher Ki67 score and higher likelihood of Glut-1 expression than those with non-pCR (p = 0.009, 0.01, 0.03, respectively). Only p-values with statistical significance were described. (Conclusion) Higher tumoral expression levels of Ki67 and Glut-1 were correlated with higher oxygenation and lower lipid concentration and associated with a pathologic complete response to chemotherapy. Non-invasive optic properties measured using DOSI are potential surrogate markers for tumor proliferation and glucose metabolism. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-01-10.
Abstract 2661: Healthcare utilization by race and sex among a nationally representative sample of adults with and without a personal history of cancer
Authors: Clinton D. Burnside, Mark D. Williams, Tamaro Hudson, Ricardo Caldera, Clyde Freeman, Luisel Ricks-Santi, Patricia O'Neal, Adeyinka 0. Laiyemo
Journal: Cancer Research (2012)

Abstract Background: Men and minorities suffer higher burdens from cancer. Healthcare utilization differences may contribute to this major public health problem. Aim: To compare utilization of healthcare services by race and sex among adults with and without a history of cancer as measured by having at least one doctor's visit within the last 12 months. Methods: We analyzed data from 7,229 responders to the 2007 Health Information and National Trends Survey (HINTS). We identified participants with and without a personal history of cancer and compared them by race and sex with having a doctor's visit within the previous 12 months. We used logistic regression models to calculate Odd Ratios (OR) and 95% confidence intervals (CI). Results: The mean age of respondents was 54.1 years, 38.8% males, 76.1% whites, 9.4% blacks, and 8.6% Hispanics. Of the respondents, 88.8% had health insurance (92.5% whites, 78.9% blacks, and 69.1% Hispanics; P value &amp;lt;0.001). Although there was no difference in health insurance coverage by sex (P value = 0.506), men were less likely to have seen a doctor within the previous 12 months (OR=0.40; 95% CI: 0.31-0.51). Cancer survivors were more likely to have seen a doctor (OR=2.70; 95% CI: 1.68-4.36), but there was no difference by race. After adjusting for age, education, race, income and insurance status, men were less likely to have seen a doctor if they did not have a personal history of cancer (Table). Conclusion: Our study suggests that men improve in their compliance to doctors’ visits only after cancer diagnosis. Targeted interventions to promote use of preventive care services by men are needed. Table: Comparison of doctors’ visit within the previous 12 months by personal history of cancer 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 2661. doi:1538-7445.AM2012-2661
Successful en bloc endoscopic submucosal dissection of a giant rectal laterally spreading adenoma
Authors: Xiaowei Tang, Bo Jiang, Wei Gong
Journal: Endoscopy (2014)

A 71-year-old woman with diarrhea and weight loss was admitted to the hospital. Colonoscopy revealed a large laterally spreading tumor in the rectum, 5 cm from the anus. The mass was approximately 14 cm long and involved approximately five-sixths of the rectal circumference. Chromo-magnification endoscopy and endoscopic ultrasonography confirmed that the lesion did not involve the submucosa. After discussion with the patient, written informed consent was obtained before she underwent endoscopic submucosal dissection (ESD).
Giant Coronary Artery Aneurysm Seen on Blood-Pool Study
Authors: Alexander Trujillo, Suthipong Soontrapa, Preeti Singh, Sharmila Sehli, Jennifer Harris, Jose A Suarez, Aliakbar Arvandi, Ralph F Paone, Gary E Meyerrose
Journal: Clinical Nuclear Medicine (2012)

An 81-year-old man was incidentally found to have a large pericardial cyst on a chest computed tomography. Before surgical removal, an echocardiogram demonstrated that the cyst was more likely a large (7.5 cm) right coronary arterial aneurysm. A cardiac blood-pool study demonstrated a blood-filled structure adjacent to the heart, roughly the same size as the combined size of both the right and left ventricles. Coronary angiography confirmed the presence of a large right coronary artery aneurysm. A coronary aneurysm should be considered when a blood-filled structure is seen adjacent to the heart on a multigated acquisition scan.1–8
Subcapsular hepatic hematoma post ERCP: a rare or an underdiagnosed complication?
Authors: F. Orellana, J. Irarrazaval, J. Galindo, P. Balbontin, L. Manríquez, R. Plass, R. Araya, H. Ríos, R. Sáenz
Journal: Endoscopy (2012)

Endoscopic retrograde cholangiopancreatography (ERCP) is a minimally invasive procedure for diagnosis and treatment of biliary and pancreatic disease that even in expert hands can have complications in 2 % – 10 % of cases, with mortality rates of 0.5 % – 1 % [1] [2]. Pancreatitis, cholangitis, perforation, and bleeding from papillotomy have been the most frequently described complications.
P08.21 * THE ROLE OF TARGETED THERAPY IN COMPLEX TREATMENT OF PATIENTS WITH BRAIN METASTASES (BM) FROM RENAL CELL CANCER (RCC)
Authors: D. R. Naskhletashvili, A. Bekyashev, V. Karakhan, V. Aleshin, E. Prozorenko, Z. Michina, S. Medvedev
Journal: Neuro-Oncology (2014)

BACKGROUND: About 2-11% of all patients (pts) with RCC develop BM, leading to a poor prognosis and a median survival of <6 months after whole brain radiotherapy. This study was designed to evaluate targeted therapy in RCC pts with BM. METHODS: Eligible pts had confirmed RCC and BM (≥1 lesion of ≥10mm diameter) aged >18 years with ECOG performanse status (PS) of 0-2. From June 2009 to January 2014, 16 pts with RCC and BM were enrolled in this study. 14 pts (87,5%) had extracranial metastases. 9 pts received sunitinib, 6 pts received sorafenib and 1 patient received pazopanib until radiologically-verified progressive disease. The primary endpoints were objective response rate (ORR) in the brain and in the extracranial lesions, progressive-free survival (PFS) and overall survival. Previous treatment: nephrectomy - 14 pts (87,5%), cytokines - 9 pts (56,3%), targeted therapy (before BM) - 4 pts (37,5%). Local control of BM: previous neurosurgery - 3 pts (18,8%), radiosurgery - 6 pts (37,5%), previous neurosurgery + radiosurgery - 3 pts (18,8%). RESULTS: ORR in the brain was 31,3% (5 partial responses). All partial responses in the brain achieved in patients who received targeted therapy and radiosurgery. Stable disease in the brain was 50,0% (8 pts). 1 patient with stable in the brain received targeted therapy and radiosurgery, 7 pts received targeted therapy. ORR in the extracranial lesions was 25,0% (4 partial responses). Stable disease in the extracranial lesions was 50% (8 pts). The median of PFS was 6 months. The median of overall survival was 10 months. CONCLUSIONS: Surgery and radiotherapy, including radiosurgery, must be considered as optimal local treatment for pts with RCC and BM. Targeted drugs have demonstrated their ability to achiеve a clinical and X-ray verified objective effect (as stabilization in most cases) in treating of pts with disseminated RCC and BM.
Abstract 4731: Cytotoxic versus cytostatic effects in tumor models by spiro-oxindole-based modulators of the MDM2-p53 interaction
Authors: Isabelle Meaux, Cédric Barrière, Donna McEachern, Stéphane Guerif, Laurent Besret, Odette Dos-Santos, Stéphane D'Agostino, Isabelle Sanchez, Dimitri Gorge-Bernat, Pascal Pannier, Nathalie Ratet, James Watters, Harry Miao, Jason Sager, Christoph Lengauer, Carlos Garcia-Echeverria, Shaomeng Wang, Lance Leopold, Laurent Debussche
Journal: Cancer Research (2012)

Abstract Two spiro-oxindole-based modulators -compounds A and B - of the MDM2-p53 protein-protein interaction display suitable pharmacological properties and are currently under advanced preclinical development (1). In vitro, these compounds induce massive cell death in a subset of relevant tumor models such as MDM2-amplified SJSA-1, while they can significantly block cell proliferation without detectable cytotoxic effect in other human cell lines (e.g. HCT116). To better characterize in vivo the different tumor cell sensitivity of these novel MDM2 antagonists, quantitative and longitudinal pharmacodynamic effects have been determined in several preclinical settings: i) anti-tumor efficacy, ii) activation of p53-dependent molecular biomarkers such as p53 itself, p21, MDM2, PUMA, Noxa, Bax and MIC-1 and iii) downstream biological effects monitored by immuno-assays as well as by in vivo fluorescence tomography and PET imaging. The results obtained from these studies have revealed striking differences in the biological read-outs associated with the observed cytotoxic versus cytostatic effects and provide guidance for the use of certain biomarkers in the clinical development of this new generation of anti-cancer agents. 1. Wang S. et al., AACR, Orlando FL, 2011, Abstract LB-204 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 4731. doi:1538-7445.AM2012-4731
ANÁLISIS EVOLUTIVO DE LA CPRE EN LA ÚLTIMA DÉCADA
Authors: R Díez Rodríguez, J Espinel Díez, M García Alvarado, L Vaquero Ayala
Journal: Endoscopy (2011)

Objetivo: Evaluar los cambios sucedidos en los últimos 8 años en cuanto a características de los pacientes, indicación, resultado obtenido y terapéutica realizada, en pacientes sometidos a una CPRE.
Regurgitation of a mass into the mouth: a fibrovascular polyp of the esophagus
Authors: A. Goto, M. Suzuki, K. Iizuka, Y. Yoshida, K. Suzuki, M. Itoh, H. Wakasugi, K. Fujii, Y. Matunaga, Y. Shinomura
Journal: Endoscopy (2010)

A 45-year-old man visited our hospital with a 6-month history of intermittent regurgitation of a mass into his mouth. Laryngoscopy revealed a smooth mass in the pharynx; this mass had prolapsed from the esophagus ([Fig. 1 a, b]).