tbuckley/cabot-search huggingface dataset:
DILATACIÓN ENDOSCÓPICA DE ESTENOSIS ESOFÁGICAS BENIGNAS: EXPERIENCIA EN 1472 PROCEDIMIENTOS
Authors: M Figueroa, A Cárdenas, JM Bordas, A Ginés, G Fernández-Esparrach, M Pellisé, B González, M López-Ceron, C Rodriguez de Miguel, J Llach, O Sendino
Journal: Endoscopy (2013)

Introducción: La dilatación endoscópica (DE) es considerada el tratamiento de elección en pacientes con estenosis esofágicas benignas (EEB). No existe un consenso absoluto acerca de cuál es la mejor técnica de dilatación así como tampoco un protocolo terapéutico bien establecido frente a los casos complejos. Objetivo: Analizar la experiencia de un centro de referencia, determinando las tasas de resolución, recurrencia, refractariedad, así como la evolución y factores asociados a éstas. Material y Método: Estudio retrospectivo de 184 pacientes con EEB sometidos a 1472 DE sin apoyo radioscópico, entre Enero 1997 y Diciembre 2012. Resultados: Se analizaron 184 pacientes, con tiempo de seguimiento medio de 45.4 meses. La etiología de la estenosis fue péptica (38%), postquirúrgica (33.7%), anillo de Schatzki (7.6%), actínica (7.1%), cáustica (4.9%) y otras etiologías (8.7%). Se logró una dilatación efectiva en 171 pacientes (92.9%) mientras que 13 (7.1%) fueron refractarios al tratamiento. De los 171 pacientes que respondieron inicialmente, 19 (10.3%) presentaron recurrencia, por lo que la resolución finalmente se logró en un 82.6% de la muestra. El número medio de dilataciones fue de 3 (1 – 7). Se encontró una relación entre la ubicación anatómica de la estenosis y la tasa de recurrencia, siendo significativamente más recurrentes las de esófago medio (p = 0.04). Además, se encontraron diferencias estadísticamente significativas entre la etiología de las estenosis y el número medio de dilataciones requeridas, requiriendo un mayor número de dilataciones las estenosis cáusticas y actínicas. Se registraron un total de 4 complicaciones (2.2% del total de pacientes/0.26% del total de procedimientos). No hubo mortalidad asociada al procedimiento. Conclusiones: La dilatación endoscópica sin apoyo radioscópico, es un método eficaz y seguro en la resolución de las EEB. Las estenosis localizadas en esófago medio presentan una mayor tasa de recurrencia. Las estenosis por cáusticos y actínicas requieren mayor número de dilataciones.
IMPACT OF PRE-PROCEDURAL SIGNIFICANT MITRAL REGURGITATION UPON MORTALITY AFTER TRANSCATHETER AORTIC VALVE INTERVENTION FOR SEVERE AORTIC STENOSIS
Authors: Maria I. Drakopoulou, Konstantinos Toutouzas, Konstantinos Stathogiannis, Archontoula Michelongona, George Latsios, Andreas Synetos, Odysseas Kaitozis, Constadina Aggeli, Eleftherios Tsiamis, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2016)
Endosonographic and elastographic features of a rare epidermoid cyst of an intrapancreatic accessory spleen
Authors: M. Khashab, M. Canto, V. Singh, R. Hruban, M. Makary, S. Giday
Journal: Endoscopy (2011)

Accessory spleens are found in approximately 10 % of the general population, of which 16 % are intrapancreatic [1]. A previously healthy 49-year-old patient was referred to our tertiary center for further evaluation of a pancreatic mass. She had initially presented to another hospital with nonspecific abdominal pain. An abdominal computed tomography (CT) scan had revealed a solid mass in the tail of the pancreas. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) was suggestive of a pancreatic neuroendocrine tumor (PNET).
Abstract 2750: Short-chain lipids catalyse intracellular drug accumulation by a transient molecular gateway that allows plasma membrane traversal
Authors: Albert J. van Hell, Dayana Martins Gueth, Manuel Nuno Melo, Siewert Jan Marrink, Marcel Verheij
Journal: Cancer Research (2012)

Abstract BACKGROUND: The lipid composition of the plasma membrane provides an effective barrier towards exogenous, potentially cytotoxic molecules. As a consequence, membrane traversal of most therapeutic drugs is sub-optimal and remains a major limitation for clinical efficacy. We previously identified a class of short-chain sphingolipids that facilitate the accumulation of amphiphilic compounds, including the cytostatic drug doxorubicin, within tumor cells, leading to improved therapy response. AIM: In order to elucidate the mechanism of action of short-chain lipids, both in vitro and model membrane studies and in silico molecular dynamics simulation experiments were designed. RESULTS: We demonstrate that short-chain sphingolipids act at the level of the plasma membrane, however, independently of lipid microdomain (raft) formation or membrane proteins. In artificial lipid membranes of well-defined compositions short-chain sphingolipids enhanced doxorubicin-membrane traversal similar to cell membranes; N-octanoyl-glucosylceramide decreased the translocation half-time of doxorubicin over liquid ordered lipid membranes by a factor 1.93 (p &amp;lt; 0.05). In case of liquid disordered membranes, a comparable effect was observed (factor 1.91; p &amp;lt; 0.05); lipid phase separation (raft formation) did not affect enhanced doxorubicin translocation. Molecular dynamics simulations revealed that the short-chain lipids act by assembling a transient molecular gateway for doxorubicin. Accordingly, the free energy barrier for the hydrophilic head group of the drug to dehydrate and translocate to the opposite side of the membrane is reduced by two-fold (p &amp;lt; 0.05). CONCLUSION: Short-chain lipids catalyse the transbilayer movement of amphiphilic cytostatic drugs to achieve higher intratumoral drug accumulation, and their action is explained by the formation of a transient lipid gateway in the plasma membrane of the tumor cell, thus facilitating drug translocation and subsequent intracellular accumulation. 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 2750. doi:1538-7445.AM2012-2750
Abstract P2-12-14: Use of the MD Anderson Symptom Inventory to Screen for Depression in Breast Cancer
Authors: EA Kvale, CB Azuero, A Azuero, M Fisch, C Ritchie
Journal: Cancer Research (2012)

Abstract Background: The prevalence of depression among breast cancer patients is estimated to be twice that in the general population, is linked to diminished quality of life and impaired adherence to therapy. Depression is frequently underdiagnosed or misdiagnosed in this population. Efficient screening for depression is central to patient-centered care and enhanced clinical outcomes for breast cancer patients. Purpose: To evaluate the use of a commonly utilized symptom assessment instrument as a screen to enhance identification of breast cancer patients experiencing depression. Methods: Data from a longitudinal surveillance database in outpatient supportive and palliative care were utilized, 174 breast cancer patient contacts were evaluated. Patients completed both the MD Anderson Symptom Inventory (MDASI) and the 9-item Patient Health Questionnaire (PHQ-9) as components of a routinely collected patient-reported outcomes battery. Performance of the MDASI (using the 1–10 Depression question) in identifying cases of depression (defined as a score ≥ 15 on the PHQ-9) was determined using receiver operating characteristic (ROC) analysis. Results: Data were available on 174 patient contacts. When scored as a continuous measure, the MDASI performed well with an area under the ROC curve of 0.87 (95% confidence interval [CI], 0.81–0.94). An MDASI cutoff score of &amp;gt;= 6 provided a sensitivity of 73% (95% CI, 58%–88%), a specificity of 80% (95% CI, 74%–87%), a positive predictive value (PPV) of 46%, and a negative predictive value (NPV) of 93%. Conclusion: The “depression” component of the MDASI as a screening instrument for depression in breast cancer patients yields suboptimal sensitivity and specificity for use as a screening tool. Further efforts to evaluate subsequent iterations of the MDASI and combinations of elements in the MDASI that may enhance performance are indicated. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-12-14.
Abstract 2965: hSSB1 binds and protects p21 from ubiquitin-mediated degradation and positively correlates with p21 in human hepatocellular carcinomas
Authors: Tiebang Kang, Shuangbing Xu, Yi-Xin Zeng
Journal: Cancer Research (2011)

Abstract Down-regulation of hSSB1, a single-stranded DNA-binding protein, causes increased radiosensitivity, defective checkpoint activation and genomic instability. However, the mechanisms of hSSB1 function in these responses remain to be uncovered. Here, we present evidence that hSSB1 and p21 interact through their N-terminal domains and that this interaction may prevent p21 from ubiquitin-mediated degradation. Furthermore, both promotion of the G1/S transition and abrogation of the G2/M checkpoints induced by hSSB1 knockdown are substantially rescued by overexpressing p21. Most importantly, hSSB1 and p21 levels are positively correlated in human hepatocellular carcinomas, as determined by immunostaining. Therefore, hSSB1 may positively modulate p21 to regulate cell cycle progression and DNA damage response, implicating hSSB1 as a novel, promising therapeutic target for cancers such as hepatocellular carcinomas. 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 2965. doi:10.1158/1538-7445.AM2011-2965
Fatal Pulmonary Hypertension Associated with Short-Term Use of Fenfluramine and Phentermine
Authors: Eugene J. Mark, Eva D. Patalas, Howard T. Chang, Richard J. Evans, Stanton C. Kessler
Journal: New England Journal of Medicine (1997)

The dangers inherent in marked obesity have prompted physicians to advocate more aggressive strategies for weight reduction. One current strategy is the prescription of fenfluramine,1,2 either alone or in combination with phentermine, with the knowledge that the risks of the drugs must be balanced against the risks of continued obesity. Pulmonary hypertension in adults has several causes that can be identified pathologically. In the case of pulmonary hypertension that develops with hypoxia during the course of chronic obstructive or interstitial fibrosing disease of the lung, the pulmonary vessels are characterized by intimal and medial hyperplasia and luminal stenosis. Thromboembolic . . .
Complete Bundle-Branch Block Complicating Acute Myocardial Infarction
Authors: M. J. Godman, B. W. Lassers, D. G. Julian
Journal: New England Journal of Medicine (1970)

Bundle-branch block complicated 68 out of 806 cases of acute myocardial infarction managed in a coronary-care unit and was associated with a mortality of 56 per cent. Twenty-five out of 48 patients with right-bundle-branch block, and 13 of 20 patients with left-bundle-branch block died. In 21 of the 68 patients complete heart block subsequently developed, and in 13 of these an idioventricular pacemaker failed to emerge. Bilateral bundle-branch block preceded the onset of complete heart block in 15 patients. Transvenous pacing electrodes were inserted prophylactically in the last 31 consecutive cases of bundle-branch block. This procedure was associated with a high proportion of life-threatening arrhythmias, and pacing did not reduce subsequent mortality in the nine patients in whom complete heart block developed.
Education and support for self care management in chronic illnesses in India
Authors: R. Devi, M. M. Singh, B. Kapoor, N. Yedla
Journal: BMJ (2014)

We agree with Iongh that patients with chronic illnesses should be supported to take care of themselves.1 

Realising the need for patient care in the home setting, Indira Gandhi National Open University in New Delhi, India, has started a certificate …
The lysyl oxidase pro-peptide attenuates fibronectin-mediated activation of the focal adhesion kinase and p130Cas in breast cancer cells.
Authors: Y Zhao, C Min, S Vora, PC Trackman, GE Sonenshein, KH Kirsch
Journal: Cancer Research (2009)

Abstract Abstract #4073 The lysyl oxidase (LOX) gene encodes an enzyme (LOX) critical for extracellular matrix maturation. The LOX gene has also been shown to inhibit the transforming activity of Ras oncogene signaling. In particular, the pro-peptide domain (LOX-PP) of the secreted precursor protein (Pro-LOX) was found to inhibit the transformed phenotype of breast, lung and pancreatic cancer cells. LOX-PP expression in these carcinoma cells reverted Her-2/neu- and Ras-mediated epithelial to mesenchymal transition (EMT), leading to increased expression of E-cadherin and γ-catenin, and reduced levels of Snail, vimentin and/or BCL2, as well as invasion through Matrigel. Furthermore, LOX-PP expression reduced tumor formation of Her-2/neu driven breast cancer cells in a xenograft model. However, the mechanism of action remains to be determined. Here the ability of LOX-PP to attenuate the integrin signaling pathway in NF639 breast cancer cells driven by Her-2/neu, which signals via Ras, was tested. Ectopic Pro-LOX and LOX-PP expression inhibited fibronectin-stimulated protein tyrosine phosphorylation. Importantly, phosphorylation of the focal adhesion kinase (FAK) on Tyr397 and Tyr576, and the activation of its downstream target p130Cas were substantially reduced. Furthermore, these changes were also reflected by a reduced amount of endogenous p130Cas in the Triton X-100 insoluble protein fraction, and attenuation of fibronectin-activated haptotaxis. Interestingly, expression of mature LOX enzyme enhanced fibronectin-stimulated integrin signaling. Of note, treatment with recombinant LOX-PP reduced haptotaxis of NF639 and human MDA-MB-231 and Hs578T breast cancer cells. Thus, the tumor suppressor function of LOX-PP is likely mediated, in part, by blocking integrin signaling and fibronectin-stimulated cell migration. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4073.
Abstract 2788: Design, optimization, and biological evaluation of potent irreversible inhibitors of BTK kinase
Authors: David J. Bearss, Sorna Venkataswamy, Steven L. Warner, Hariprasad Vankayalapati, Jared J. Bearss, Sunil Sharma
Journal: Cancer Research (2011)

Abstract Bruton's tyrosine kinase (BTK) is a cytoplasmic nonreceptor tyrosine kinase belonging to the Tec family of kinases. Critical for its function, BTK contains a pleckstrin homology (PH) domain and Src homology SH3 and SH2 domains. It signals downstream of the B-cell receptor (BCR) and is centrally involved in B-cell development. Activation of B-cells by various ligands is accompanied by the translocation of BTK to the cell membrane where it binds phosphatidylinositol-3,4,5-trisphosphate through its PH domain. Activation of BTK results in downstream signaling through the PI3K/AKT, PLCγ, NFκB, and other signaling pathways important for B-cell development and function. Recent reports have shown the aberrant expression and function of BTK in some cancers, including B-cell malignancies. We describe here the design, synthesis, molecular modeling, and biological evaluation of a series of small molecule, inhibitors of BTK kinase. Our initial lead compounds were identified via cross-docking experiments utilizing the crystal structure of BTK kinase and screening a previously in-house explored kinase inhibitor scaffold. We subsequently carried out structure-activity relationship studies and optimized the lead structures, which have IC50 activities in the range of 1 to 10μM against BTK. A critical step in the optimization of this chemical series against BTK was to explore the possibility of adding a Michael's acceptor group to react with Cys481 in the ATP-binding pocket of BTK. Optimization efforts yielded the currently best leads, HCI-1684 and HCI-1685, which inhibit BTK with IC50 values of 12 and 45 nM, respectively. Modeling data suggest these compounds irrepressibly bind in the ATP-binding pocket of BTK. HCI-1684, HCI-1685 and other lead compounds were further evaluated in cell-based assays and were demonstrated to inhibit BTK function downstream of BCR activation. This series of BTK inhibitors were shown to decrease phospho-PLCγ1/2 levels and other downstream phosphorylation events in malignant B-cell cell lines, such as Ramos B. Compound optimization and biological evaluation of this chemical series and evaluation in animal pharmacodynamic endpoint studies will be presented. Taken together, these results suggest BTK is a potential therapeutic target in cancer and that HCI-1684 is an exciting agent to potentially treat B-cell malignancies 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 2788. doi:10.1158/1538-7445.AM2011-2788
Abstract 1403: Multiorogan metastasis of human HER-2+ breast cancer in immunodeficient mice
Authors: Pier-Luigi Lollini, Giordano Nicoletti, Marianna Ianzano, Stefania Croci, Valentina Grosso, Arianna Palladini, Manuela Iezzi, Lorena Landuzzi, Carla De Giovanni, Patrizia Nanni
Journal: Cancer Research (2012)

Abstract Metastatic spread is the major cause of morbidity and death among cancer patients. In vivo studies of the metastatic process are severely hampered by the fact that most human tumor cell lines derived from highly metastatic tumors, such as human HER-2+ breast cancer, fail to consistently metastasize in immunodeficient mice like athymic nude mice. We studied whether a highly immunodeficient double knockout mouse, Rag2−/−;Il2rg−/−, which lacks T, B and NK cell activity, was more permissive to metastatic spread than the nude mouse. Metastatic dissemination in Rag2−/−;Il2rg−/− mice was widespread, and reached all sites commonly affected in human patients, including lungs, liver, bones and brain. Interestingly, metastatic spread from local tumors was only marginally different between tumors growing orthotopically or subcutaneously, both for what concerned the more malignant MDA-MB-453 cell line and the less malignant BT-474. Intravenous administration of cells significantly enhanced the metastatic spread of BT-474 cells, with the proportion of affected mice attaining 100%. Different metastatic burdens were observed in different organs, and the use of EGFP-tagged cells was instrumental in allowing a precise detection of metastatic deposits in bones, liver and brain. Quantitative evaluation of metastatic spread in Rag2−/−;Il2rg−/- mice was not limited to EGFP detection, for example we used qPCR with human-specific primers to quantitate metastatic burden in the brain, and flow cytometry to detect HER-2-positive disseminated tumor cells in the bone marrow. The brain is a common site of metastatic spread, but tumor growth in immunodeficient mice fails to reproduce this fateful property of human tumors, unless unique cell lines, selected variants and/or special injection routes are used. In contrast, spontaneous brain metastases from local tumors were common in Rag2−/−;Il2rg−/- mice, and their frequency reached 100% after intravenous injection. Morphologic analysis of brain deposits showed that multiple metastases were present, both intracerebral and intraventricular or leptomeningeal, ranging from minimal deposits of few cells to huge masses. In conclusion, human HER-2+ human breast cancer cells in Rag2−/−;Il2rg−/− mice faithfully reproduce the multiorgan metastatic pattern observed in patients, thus allowing the investigation of metastatic mechanisms and the preclinical study of novel antimetastatic agents. 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 1403. doi:1538-7445.AM2012-1403
AB1178-HPR Hand Exercise Intervention in Patients with Polymyositis and Dermatomyositis: A Pilot Study
Authors: M. Regardt, M.-L. Schult, Y. Axelsson, A. Aldehag, H. Alexanderson, I.E. Lundberg, E. Welin Henriksson
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To develop a 12-week hand exercise intervention for patients with polymyositis (PM) and dermatomyositis (DM) and evaluate adherence, patients opinion of program design and overall feasibility and the effect on hand function and activity limitation after the intervention. <h3>Methods</h3> A pilot, hand exercise intervention was conducted on a convenience sample of 15 patients with reduced handgrip strength and established, inactive PM and DM. Acceptable adherence was set at 75%. The program was evaluated based on patients9 opinions regarding exertion, the movements and over all feasibility. Hand- and pinch-grip strength, grip ability, dexterity and activity limitation were assessed. <h3>Results</h3> Eleven of 15 patients completed the intervention with acceptable adherence of 78–100%. Measures of handgrip strength, dexterity and activity limitation were reduced at baseline. Throughout the intervention, exertion was rated between "moderate" and "somewhat strong". Finger abduction and adduction were excluded from the program because they were not feasible. Repetitions increased continuously to a maximum of 30 repetitions per movement. Patients regarded this as too time-consuming and suggested 10 repetitions daily or 10–20 repetitions 2–4 times per week. There were some individual, clinically meaningful improvements in hand function and activity limitation. After the intervention, three-jaw pinch grip strength (left hand) had improved. <h3>Conclusions</h3> A hand exercise program was feasible to perform by patients with established PM or DM. The effect was limited with few individual improvements in hand function and activity limitation, indicating a need to increase the resistance in the movements and to limit the time spent. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2230
Phase I Study of an AKT Inhibitor (MK-2206) Combined with Lapatinib in Adult Solid Tumors Followed by Dose Expansion in Advanced HER2+ Breast Cancer
Authors: Kari B. Wisinski, Amye J. Tevaarwerk, Mark E. Burkard, Murtuza Rampurwala, Jens Eickhoff, Maria C. Bell, Jill M. Kolesar, Christopher Flynn, Glenn Liu
Journal: Clinical Cancer Research (2016)

Preclinical data support combining AKT inhibitors with HER2-targeted therapies to overcome resistance to treatment. This phase I study combined the investigational AKT inhibitor, MK-2206, with lapatinib to determine the MTD.The dose escalation cohort enrolled adults with advanced solid tumors, who received MK-2206 dosed 30 to 60 mg every other day and lapatinib 1,000 to 1,500 mg daily continuously, escalated using a 3+3 design. Cycles were 28 days except cycle 1 (35 days, including an initial 8 days of MK-2206 alone to evaluate pharmacokinetic interactions). The dose expansion cohort enrolled adults with advanced HER2(+) breast cancer.Twenty-three participants enrolled in the dose escalation cohort. Dose-limiting toxicities were hyponatremia, fatigue, rash, hypocalcemia, and mucositis. Common toxicities included diarrhea, nausea, and rash. The MTD was reached at MK-2206 45 mg orally every other day and lapatinib 1,500 mg orally daily. Two participants maintained stable disease for >4 months, including a colorectal cancer participant with substantial carcinoembryonic antigen decrease. Of 5 participants in the dose expansion cohort, 2 maintained stable disease for >6 months, including one with prior progression on single-agent lapatinib. Plasma MK-2206 concentrations decreased after addition of lapatinib, but in vitro studies indicate lapatinib increases the intracellular levels of MK-2206.MK-2206 combined with lapatinib can be tolerated with both drugs above biologically active single-agent doses. Overlapping toxicities result in significant diarrhea and rash, which can be managed medically. Antitumor activity was promising and supports evaluation of AKT inhibitors combined with HER2-targeted therapies. Clin Cancer Res; 22(11); 2659-67. ©2016 AACR.