tbuckley/cabot-search huggingface dataset:
BLOOD BIOMARKERS TO PREDICT MAGNETIC RESONANCE IMAGING INFARCT SIZE, LEFT VENTRICULAR EJECATION FRACTION AND MORTALITY AFTER ST-ELEVATION MYOCARDIAL INFARCTION
Authors: Minke Hartman, Ruben Eppinga, Pieter-Jan Vlaar, Chris Lexis, Erik Lipsic, Joost Haeck, Dirk van Veldhuisen, Iwan Van Der Horst, Pim van der Harst
Journal: Journal of the American College of Cardiology (2016)
Case 32-2002
Authors: Jayaraj Rajagopol, Eugene J. Mark
Journal: New England Journal of Medicine (2002)

Presentation of CaseA 58-year-old man was admitted to the hospital because of interstitial pulmonary disease.The patient had a history of eosinophilic granuloma, which had been confirmed by right-sided open-lung biopsy 25 years earlier at another hospital and had been treated with prednisone for approximately 1 year. When the medication was discontinued, the patient resumed smoking cigarettes, so that he ultimately had more than a 25-pack-year history. Five years before admission, he had a “stroke” that impeded his speech for three or four months, with subsequent recovery. One and a half years before admission, he had a single episode . . .
EFICACIA CLÍNICA DE LA INSERCIÓN DE VARIAS PRÓTESIS COAXIALES COLÓNICAS TRAS SU DISFUNCIÓN EN EL CÁNCER DE COLON
Authors: N Alcaide Suárez, L Sancho del Val, R Ruiz-Zorrilla, AL Vargas, I Peñas Herrero, J Barrio Andrés, C Herrero Quirós, C De la Serna Higuera, M Pérez-Miranda
Journal: Endoscopy (2012)

Introducción: Las prótesis metálicas autoexpansibles (PMA) utilizadas en el tratamiento paliativo de la obstrucción maligna de colon han demostrado su eficacia clínica. No se ha establecido cuál es el tratamiento de elección tras su disfunción. Objetivo: Evaluar la eficacia clínica de la inserción de dos o más prótesis coaxiales tras su disfunción. Métodos: Análisis retrospectivo de 92 pacientes, identificados mediante base de datos prospectiva, durante 24 meses. Número de prótesis utilizadas: 113. Intento de colocar segunda prótesis coaxial en 15 (11 varones (73.3%), edad media 78 años (rango 45–94). Determinación del éxito técnico y clínico, permeabilidad y complicaciones. Resultados: Adenocarcinoma de colon: 14 (93.3%), metástasis de cáncer gástrico: 1 (6.7%). Localización de la obstrucción: 5 (33.3%) recto, 6 (40%) sigma, 3 (20%) colon descendente y 1 (6.6%) ángulo hepático. Carcinomatosis radiológica/quirúrgica: 3 (20%). Funcionalidad 1° stent: 152días (1–820) Colocación de 2° stent: 13, 10 (77%) ingrowth, 2 (15.4%) angulación y 1 (7.7%) migración distal. Fallo técnico: 2 (13.3%). 3 (23.1%) sin éxito clínico, 2 tenesmo y 1 perforación. Seguimiento del 2° stent: 48días (2–150), 17días (2–37días) en los 5 que fallecieron como consecuencia de la evolución de su enfermedad y 96días (57–150días) en el resto, ingrowth en 4 (80%) y uno permeabilidad actual. Colocación de 3° stent en 3 (75%) y fallo técnico en 1, seguimiento de 101días (39–186), un éxitus, una perforación y una colostomía quirúrgica tras un 4° stent con permeabilidad de 46días y 5° stent durante 87días. Conclusiones: La permeabilidad de las PMA en colon disminuye a medida que se colocan stents coaxiales. Constituyen un adecuado tratamiento paliativo, con alto porcentaje de éxito clínico y escasas complicaciones, evitando una intervención quirúrgica en pacientes con esperanza de vida corta. Los resultados de este estudio sugieren que la colostomía puede considerase cuando se produce un tercer episodio de obstrucción.
Abstract 702: Drug resistance and invasion in diffuse large B-cell lymphoma are mediated by Akt, 14-3-3ζ, and Vimentin
Authors: Evan M. Cherry, Kayla J. Bayless, Steve A. Maxwell
Journal: Cancer Research (2011)

Abstract Acquired multi-drug resistance to the anthracycline-based CHOP chemotherapy is a major cause of unsuccessful treatment and mortality in 40% of diffuse large B-cell lymphoma (DLBCL) patients. To investigate molecular mechanisms of multidrug resistance, we generated CHOP-resistant DLBCL cells through repeated selection in the presence of a clinically-relevant CHOP cocktail (cyclophosphamide, doxorubicin, vincristine, prednisone at the ratio of 80:5.5:0.16:11.1). Differential protein expression between CHOP-sensitive and CHOP-resistant DLBCL cells was investigated by two-dimensional differential in-gel (DIGE) analysis, which identified 10 differentially-expressed proteins related to glycolysis (Triosephosphate isomerase-1, Enolase-1), cytoskeletal structure (Ezrin, Vimentin, Tubulin-specific chaperone B), purine biosynthesis (Serine hydroxymethyltransferase), calcium-binding (Sorcin), and apoptosis (p53, 14-3-3zeta, Akt). Upregulation of Akt, 14-3-3ζ, and Vimentin was observed by Western blotting in CHOP-resistant cells compared to CHOP-sensitive cells. These proteins were also heterogenously upregulated in primary DLBCL tissues relative to normal lymphatic tissue. Our previous studies showed that siRNA-mediated knockdown of 14-3-3ζ reversed CHOP resistance in DLBCL cells (Maxwell et al [2009] J. Biol. Chem. 284:22379-89). Our current study showed that chemical Akt inhibition overcame CHOP resistance in DLBCL cells and CHOP-resistant cells exhibited a five-fold greater ability to invade collagen matrices than CHOP-sensitive cells. Moreover, knockdown of Vimentin by siRNA or inhibition by Withaferin A decreased invasion capacity of the CHOP-resistant cells in collagen matrices. The data indicate activation of an Akt-14-3-3ζ-mediated signaling pathway as a contributor to the multi-drug resistant phenotype associated with vimentin-dependent invasive behavior in DLBCL cells. 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 702. doi:10.1158/1538-7445.AM2011-702
Abstract 1845: ADAM10: A new player in breast cancer progression
Authors: Maeve Mullooly, Patricia M. McGowan, Sumainizah Sukor, Stephen F. Madden, Enda McDermott, John Crown, Michael J. Duffy
Journal: Cancer Research (2012)

Abstract Background: The ADAMs are a family of proteases, best known for their role in releasing the extracellular domain of transmembrane proteins. One of the ADAMs, i.e., ADAM10, is involved in the activation of 2 important signaling systems controlling cell growth, invasion and metastasis, i.e. the EGFR and NOTCH signaling systems. Because of its ability to activate both EGFR and NOTCH, ADAM10 is likely to play a role in cancer formation or progression. The aim of this study was therefore to investigate the role of ADAM10 in breast cancer and test its therapeutic potential, especially in patients with the triple-negative form of this disease. Materials and Methods: ADAM10 mRNA expression was examined in a pooled collection of publically available databases (n ∼ 4000). ADAM10 protein was examined in a cohort of 120 breast tumor extracts by ELISA. In addition, ADAM10 expression was decreased by RNAi and the effects of this on cell proliferation, invasion and migration were determined. Using the novel ADAM10 inhibitor GI254023X (GSK), we examined the effect of ADAM10 inhibition on a panel of 13 breast cancer cell lines. Results: Using the pooled collection of databases, ADAM10 mRNA was found to be significantly elevated in HER2+ breast cancer compared to other subtypes (p &amp;lt; 0.0001). High ADAM10 mRNA expression was also observed in basal like breast cancer and was associated with poorer overall survival in this subgroup (p = 0.0196). In a cohort of 120 breast tumor extracts, ADAM10 protein was found to be significantly higher in ER-negative compared to ER-positive tumors (p = 0.005), in high grade versus low grade tumors (p &amp;lt; 0.0001), and in younger than older women (p = 0.018). Downregulation of ADAM10 in MDA-MB-231 breast cancer cells resulted in a significant reduction in invasion (p = 0.0006) and cellular migration (p = 0.0002). Treatment of 13 breast cancer cell lines with GI254023X resulted in variable growth inhibition (from 0 to 52%). Furthermore, GI254023X significantly decreased invasion in the MDA-MB-231 cell line (p = 0.001). Conclusions: Our findings of a correlation between ADAM10 and features of aggressive disease and the fact that its downregulation/inhibition decreased growth, invasion and migration suggests that this ADAM10 protease is involved in the progression of breast cancer. Inhibition of ADAM10 with GI254023X may be a new treatment for breast cancer. Acknowledgements: The authors thank SFI and the Molecular Therapeutics for Cancer Ireland (SRC award, 08/SRC/B1410 to MTCI) for funding this work. 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 1845. doi:1538-7445.AM2012-1845
A4.13 The DOT1L protein and gene network in chondrocytes identifies H3K79 histone methylation as key regulator of WNT and other growth factor cascades
Authors: S Monteagudo, F Cailotto, RJ Lories
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> DOT1L is the only known H3K79 histone methyltransferase. Genome-wide association and functional studies identified the DOT1L gene to be associated with cartilage thickness and hip osteoarthritis (OA) and showed an interaction of DOT1L with canonical Wnt signalling. Here, we further investigated the biology of DOT1L in cartilage health and disease. Specifically, our objective was to define the transcriptional complexes and transcriptome associated with DOT1L in articular cartilage, and to investigate the role of DOT1L during the loss of phenotype of the articular chondrocyte. <h3>Methods</h3> Human articular chondrocytes (hACs) stimulated or not with LiCl were used to carefully map the presence or absence of DOT1L protein complexes suggested earlier in leukaemia cells, using immunoprecipitation experiments. To elucidate the transcriptional network of DOT1L, we performed a microarray of hACs from 5 non-OA fracture patients treated with a specific DOT1L inhibitor (EPZ5676) or vehicle. To establish the role of DOT1L in the maintenance of hACs phenotype, hACs were cultured in monolayer in the presence or absence of EPZ5676, and RNA and protein were isolated at serial passages. We analysed by quantitative PCR the gene expression of known genes important for chondrocyte biology and/or genes that appeared in the microarray of DOT1L inhibition. Activation of the Wnt canonical and non-canonical signalling cascades was analysed by Western blot. <h3>Results</h3> The presence of different DOT1L elongation complexes was confirmed in hACs. In the microarray, chondrocyte differentiation-associated genes, such as ACAN, RGS5, GDF10 and LOXL2 were down-regulated in EPZ5676 treated samples; OA-related genes, such as MMP1, CCL7, CCL8 and GPNMB were up-regulated; and WNT target genes, ligands and antagonists such as LEF1, WNT5A and DKK1 were significantly up-regulated. In the de-differentiation experiment, genes involved in relevant pathways for cartilage biology such as the WNT, NOTCH and BMP pathways exhibited significant changes that were highly accentuated by DOT1L inhibition. <h3>Conclusions</h3> Our transcriptomic, protein and gene interaction approach provides novel insights into the DOT1L molecular network and its putative role in osteoarthritis and cartilage. These data further support an important role for DOT1L in joint homeostasis as a key regulator of WNT signalling and other growth factor cascades in the joint.
742 EFFICACY AND SAFETY OF ENTECAVIR (ETV) PROPHYLAXIS IN INACTIVE HBV CARRIERS WHO UNDERWENT CHEMOTHERAPY FOR SOLID OR HAEMATOLOGICAL CANCER: INTERIM ANALYSIS OF A COHORT STUDY
Authors: V. Di Marco, E. Angelucci, A. Pietrangelo, F. Salerno, G.A. Niro, B. Daniele, M. Vinci, E. Villa
Journal: Journal of Hepatology (2013)
Abstract 2111: Characterization of current and novel biomarkers of bladder cancer
Authors: Elizabeth Fowler, Julie Woolworth, Yuan Shao, Philip Sobolesky, Thomas Keane, Daynna Wolff, Dennis Watson, Omar Moussa
Journal: Cancer Research (2012)

Abstract Bladder cancer is one of the most common cancers in industrialized countries. It is reported that 3.51 billion dollars are spent each year on bladder cancer treatment making it the most expensive cancer to treat on a per patient basis. Approximately 80% of bladder cancer patients have at least one reported recurrence thereby prompting meticulous lifetime screening and surveillance by health care professionals. Therefore, careful evaluation of our institution's current fluorescent in situ hybridization surveillance tools in addition to investigation of novel biomarkers is imperative. Our investigation of novel biomarkers focused on apoptosis regulating genes which are often unbalanced in cancerous tissues. Our institution recently adopted BioView, an automated FISH capture/analysis system, to replace the manual protocol. Validation and assessment of the automated system for fluorescent in situ hybridization (FISH) interpretation to detect urothelial cancer was determined using patient cases to evaluate concordance, overall positivity, interpretative time spent, sensitivity, and specificity. To evaluate novel biomarkers, mRNA from patient samples was reversed transcribed to cDNA then utilized for biomarker quantification by RT-PCR. In addition, immunohistochemistry was performed on the most promising gene to further confirm its clinical usefulness. The automated BioView capture/ detection system does prove to be more time efficient and accurate when addressing all parameters described. In evaluation of novel biomarkers, API5, BIRC3, BIRC4, SURVIVIN, and BFAR provided the most promising data with sensitivity and specificity percentages all ranging from 83% to 97%. From this study of bladder cancer markers, we focused on API5 and its role in bladder cancer initiation and progression. API5 is strongly expressed early in tumorigenesis. Our data confirm that the automated FISH capture/detection system improves laboratory efficiency and accuracy. Furthermore, our data indicate that apoptotic regulators are promising biomarkers for clinical use. In addition, API5 is expressed early in tumorigenesis, which makes it an ideal early diagnostic marker. We have noticed increase in the level of API5 protein associated with tumor grade and stage which also suggest that API5 might be a potential prognostic marker for bladder cancer. In conclusion, detection of apoptosis regulating genes is a promising diagnostic and prognostic approach to aid our screening and surveillance tools. 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 2111. doi:1538-7445.AM2012-2111
Underrepresentation of Patients 65 Years of Age or Older in Cancer-Treatment Trials
Authors: Laura F. Hutchins, Joseph M. Unger, John J. Crowley, Charles A. Coltman, Kathy S. Albain
Journal: New England Journal of Medicine (1999)

Studies have documented the underrepresentation of women and blacks in clinical trials, and their recruitment is now federally mandated. However, little is known about the level of participation of elderly patients. We determined the rates of enrollment of patients 65 years of age or older in trials of treatment for cancer.
AB1098 Obesity and insulin resistance in fibromyalgia patients
Authors: R.D. Grembiale, F. Ursini, C. Bruno, F. Savarino, S. Naty
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Fibromyalgia is a chronic disorder of uncertain etiology characterized by widespread pain and reduced threshold to pressure and other stimuli. Scientific evidences show a relationship between fibromyalgia and obesity. Insulin resistance, a key feature of obesity and metabolic syndrome (MS), is a now well-recognized cardiovascular risk factor. <h3>Objectives</h3> Objective of the study was to evaluate insulin resistance in fibromyalgia patients compared with age- and sex- matched healthy women. <h3>Methods</h3> For the present study 53 consecutive fibromyalgia female patients referred to the Internal Medicine Unit, University of Catanzaro (Italy) for chronic widespread pain were recruited. Fibromyalgia was diagnosed by a single specialist according to 1990 American College of Rheumatology (ACR) Criteria [1]. For comparison, 50 healthy age- matched female subjects were used. Body mass index (BMI), blood insulin and glucose were measured after overnight fasting. HOMA-IR, a surrogate measure of insulin resistance, was calculated as previously described by Matthews et al. [2] <h3>Results</h3> Mean age was 58.3±6.9 for patients and 56.6±7.4 for controls (p&gt;0.05). Patient's BMI and HOMA-IR, an indirect measure of insulin resistance, were significantly higher compared to healthy age- matched controls (p&lt;0.01 and p&lt;0.05 respectively). <h3>Conclusions</h3> Fibromyalgia patients have a higher degree of insulin resistance compared to healthy age-matched controls. <h3>References</h3> Wolfe, F., et al., The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum, 1990; 33(2): p. 160-72. D.R. Matthews, J.P.Hosker. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man Diabetologia 1985;28: 412-9 <h3>Disclosure of Interest</h3> None Declared
PROGNOSIS AFTER AORTIC VALVE REPLACEMENT IN PATIENTS WITH LOW GRADIENT SEVERE AORTIC STENOSIS
Authors: Risa Fukumoto, Keitaro Mahara, Yuki Izumi, Ota Mitsuhiko, Kanako Kishiki, Toshihiro Fukui, Jun Umemura, Shuichiro Takanashi, Tetsuya Sumiyoshi, Hitonobu Tomoike
Journal: Journal of the American College of Cardiology (2015)
AT-47 * PHASE I TRIAL OF INTRATHECAL TRASTUZUMAB IN HER2 POSITIVE LEPTOMENINGEAL METASTASES
Authors: J. Raizer, E. Pentsova, A. Omuro, N. Lin, L. Nayak, E. Quant, P. Kumthekar
Journal: Neuro-Oncology (2014)

INTRODUCTION: Trastuzimab is a humanized monoclonal antibody against Her2 whose limitation is central nervous system penetration that often leads to brain and leptomeningeal metastases (LM) in the setting to controlled systemic HER2 positive breast cancer. We performed a phase I clinical trial of intrathecal (IT) trastuzumab in patients with HER2 positive breast cancer and LM. METHODS: IRB consented patients were treated at defined dose levels; protocol was modified to accelerate dose escalation and increase IT dosage. Dose levels of IT treatment 10 mg, 20 mg, 40 mg, 60 mg and 80 mg were examined. Treatment was given twice a week x4 weeks, then once a week x4 weeks then every other week until progressive disease. MRI was done at 4 week intervals x2 then every 8 weeks. CSF was assessed every other week x2 then every 4 weeks. RESULTS: 13 women with HER2 positive breast cancer, 1 man with a glioblastoma, and one woman with anaplastic ependymoma were enrolled with a median age of 55 (42-67) and median KPS of 80 (60-90). Three patients were treated at the 10mg dose level, three at 20mg, one at 40mg, one at 60mg and 7 at 80mg. At the 80 mg dose level a patient was added as one patient was removed before complete evaluation and another patient had a grade 4 DLT of arachnoiditis. One patient had the Ommaya reservoir removed for infection unrelated to treatment. Data on CSF levels shows therapeutic levels in the patients treated with 10 mg, 20 mg and 40 mg; data analysis on CSF at 60 and 80 mg is pending. CONCLUSION: IT Trastuzumab is well tolerated up to 80 mg IT. Complete CSF PK data will be presented. A phase II study is underway at the 80 mg dose.
Suppression of prolactin by dopamine agonists in schizophrenics and controls
Authors: J Rotrosen, B Angrist, C Clark, S Gershon, F S Halpers, E J Sachar
Journal: American Journal of Psychiatry (1978)

Prolactin levels were determined in plasma samples obtained before and after administration of apomorphine or L-dopa to otherwise unmedicated chronic schizophrenic patients or control subjects. Basal prolactin levels did not differ in these two groups. Suppression of prolactin levels after each dopamine agonist was highly significant. Suppression in schizophrenics was slightly less than in controls following apomorphine and slightly greater following L-dopa. The authors discuss the implications of these findings as well as the limitations of the prolactin regulatory system as an index of dopamine agonist sensitivity.
P4-17-08: Is Cranial Magnetic Resonance Imaging (MRI) Necessary for Staging of Asymptomatic HER2−Positive Breast Cancer Patients?
Authors: MA Kaplan, A Inal, M Kucukoner, Z Urakci, A Isikdogan
Journal: Cancer Research (2011)

Abstract Background Breast cancer one of the most common tumors of the adults. Approximately 20% to 25% of all breast cancers are HER2−positive. It can be assumed that up to 30% of HER2−positive metastatic breast cancer (MBC) patients may experience brain metastasis during the course of their disease. The aim of this study to investigate that whether cranial MR is necessary for staging in asymptomatic HER2−positive breast cancer patients. Material and metods: HER2−positive breast cancer patients without symptoms of brain metastasis included in the study. Cranial MRI was added to the staging procedures. Subgroup analysis was performed to determine risk factors for developing brain metastasis. Results: Seventy five patients included in the study. Of whom, 71 were women (94.7%). Median age was 42.5 (22-76). Ten of the 75 patients (13.3%) had brain metastasis. The distribution rate of brain metastasis according to breast cancer stage at diagnosis was: 0% for stage I, 9.1% for stage 2, 4.3% for stage 3 and 28.6% for stage 4 (p=0.027). There was no association between presence of brain metastasis and the site of metastasis, estrogen and progesterone receptor positivity, grade, histological subgroup, menopausal status and gender. Discussion: Brain metastasis is an important problem for breast cancer patients. Treatment strategies may vary in the presence of brain metastasis. In our study we found brain metastasis nearly one quarter of patients with metastatic HER2−positive breast cancer. Cranial MRI imaging can be performed routinely in patient with metastatic HER2−positive breast cancer patients. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-17-08.