tbuckley/cabot-search huggingface dataset:
Synergistic Anticancer Effect of Peptide‐Docetaxel Nanoassembly Targeted to Tubulin: Toward Development of Dual Warhead Containing Nanomedicine
Authors: Saswat Mohapatra, Abhijit Saha, Prasenjit Mondal, Batakrishna Jana, Subhajit Ghosh, Atanu Biswas, Surajit Ghosh
Journal: Advanced Healthcare Materials (2016)

Microtubule dynamics play a crucial role in cancer cell division. Various drugs are developed to target microtubule. Although a few of them show potential in treatment of cancer, but success rate is limited due to their poor bioavailability and lack of specificity. Thus, development of highly bioavailable and target specific anticancer drug is extremely necessary. To address these key issues, here, a combination of approaches such as development of a dodecapeptide-docetaxel nanoassembly targeted to tubulin and MUC1 (mucin 1, cell surface associated glycoprotein) targeting oligonucleotide aptamer conjugated liposome for delivering peptide-docetaxel nanoassembly into the breast cancer cell have been demonstrated. These studies reveal that the peptide forms nanoassembly and entraps docetaxel drug. Further, the liposomal formulation of peptide-docetaxel exerts synergistic anticancer effect, activates key mitotic check point proteins, and inhibits bipolar spindle formation, metastatic cancer cell migration, and growth of tumor mimicking 3D multicellular spheroid.
TCT-362 Transradial diagnostic and therapeutic coronary catheterization for patients with NSTEMI or UAP using one 4.0-Fr sheath and one Sheathless Eaucathe guide catheter via one puncture site: 1-1-1 Trial
Authors: Kazunori Horie, Norio Tada, Isawa Tsuyoshi, Takashi Matsumoto, Taku Honda, Tatsushi Ohtomo, Naoto Inoue
Journal: Journal of the American College of Cardiology (2016)
Significance of metastasectomy for urothelial carcinoma
Authors: Hiroaki Iwamoto, Kouji Izumi, Takahiro Nohara, Kazutaka Narimoto, Satoru Ueno, Yasuhide Kitagawa, Yoshifumi Kadono, Hiroyuki Konaka, Atsushi Mizokami, Mikio Namiki
Journal: Annals of Oncology (2015)
Androgen-dependent regulation of Her-2/neu in prostate cancer cells
Authors: R. Berger, D. I. Lin, M. Nieto, S. Signoretti, W. C. Hahn, M. Loda
Journal: Journal of Clinical Oncology (2006)

10099 Background: The mechanisms underlying the progression of prostate cancer to androgen independence remain poorly understood. Overexpression of Her-2/neu (c-ErbB2) activates the androgen receptor pathway and confers a survival and growth advantage to prostate cancer cells in an androgen-deficient milieu. Methods: Androgen-sensitive prostate cancer cell line LNCaP was used as a model system in vitro and in vivo. Experiments in mice were undertaken by injecting cells orthotopically into the ventral lobe of the mice prostate. Results: Here, we report that androgen receptor (AR) and Her-2/neu reciprocally regulate each other in LNCaP human prostate cancer cells. Absence of androgens, AR blockade with Casodex (bicalutamide) or suppression of AR with RNAi induced Her-2/neu protein expression and phosphorylation in vitro and in vivo. Similarly, suppression of Her-2-neu expression resulted in AR upregulation. In contrast, upon re-administration of androgens, Her-2/neu mRNA, protein and phosphorylation levels decreased linearly with increasing concentrations of androgens as LNCaP cells re-entered the cell cycle. Conclusions: Thus, induction and activation of Her-2/neu occurs in an androgen-depleted environment or as a result of AR inactivation, promoting androgen-independent survival of prostate cancer cells. No significant financial relationships to disclose.
Response by Álvarez-García et al to Letters Regarding Article, “Electrophysiological Effects of Selective Atrial Coronary Artery Occlusion in Humans”
Authors: Jesús Álvarez-García, Miquel Vives-Borrás, Pedro Gomis, Jordi Ordoñez-Llanos, Andreu Ferrero-Gregori, Antoni Serra-Peñaranda, Juan Cinca
Journal: Circulation (2016)

or both of the 2 atrial chambers.Nevertheless, we certainly agree with Dr Baranchuk on the potential different clinical consequences of intra-atrial and interatrial block, the latter perhaps carrying greater hemodynamic impairment or even greater propensity to arrhythmogenesis.
TCT-384 Contrast-Induced Acute Kidney Injury and Persistent Renal Damage: Early Predictors after Coronary Angiography and Interventions
Authors: Gabriele Pesarini, Roberto Scarsini, Silvia Maggio, Anna Piccoli, Annachiara Benini, Carlo Zivelonghi, Corrado Vassanelli, Flavio Ribichini
Journal: Journal of the American College of Cardiology (2016)
Abstract 4819: Differential evolution of tumor heterogeneity in leiomyosarcomas and liposarcomas suggested by genomic profiling
Authors: Ali Amin-Mansour, Stefano Sioletic, Scott L. Carter, Levi A. Garraway, George D. Demetri, Suzanne George, Eliezer M. Van Allen, Andrew J. Wagner
Journal: Cancer Research (2015)

Abstract Sarcomas represent a heterogeneous set of malignant tumors originating from mesenchymal cells. Liposarcomas (LPS) and Leiomyosarcomas (LMS) are two of the most common histotypes, accounting for approximately 25% and 30% of all soft tissue sarcomas, respectively. The most frequent form of LPS is represented by a spectrum of disease including well-differentiated LPS (WDLPS), a non-metastasizing but locally recurrent disease with adipocytic differentiation, and de-differentiated LPS (DDLPS), an aggressive, frequently metastasizing high grade sarcoma which can arise in conjunction with elements of WDLPS. Besides the known oncogenic KIT or PDGFRA driver mutations in GIST, somatic alterations in RB1, deletions in PTEN, MDM2 amplifications in LPS, and TP53 mutations in LMS are the most commonly reported genomic aberrancies identified in sarcomas. Both WDLPS and DDLPS share amplification of 12q13-15, a genomic region containing the MDM2 and CDK4 loci, yet little is understood about the other genetic processes that yield such different phenotypes. In LMS, recurrent mutations in TP53 have been identified, but a detailed analysis of primary and metastatic tumors has not previously been described. To evaluate genetic events in these transitions, we performed whole exome sequencing (WES) on trios comprising normal tissue, WDLPS, and DDLPS obtained from individual patients (n = 19), as well as on trios of normal tissue, primary and metastatic LMS tumors obtained from separate individual patients (n = 8). Consistent with prior reports of the molecular characterization of LPS, we observed arm-level amplifications in Chr 12 in all LPS samples, and Chr 17 amplification in many LMS cases. There were no shared somatic alterations across paired WDLPS and DLPS pairs from individual patients aside from the common Chr 12 amplification (MDM2 &amp; CDK4). A higher mutation rate was observed in LMS, and there were many clonal somatic alterations shared between the primary and metastatic lesions of individuals. This study demonstrates the heterogeneity of evolution between different subtypes of sarcomas using whole exome sequencing of clinical specimens. This finding has implications for better understanding of the molecular drivers of these tumors and opportunities to identify subtype-specific therapeutic targets. Citation Format: Ali Amin-Mansour, Stefano Sioletic, Scott L. Carter, Levi A. Garraway, George D. Demetri, Suzanne George, Eliezer M. Van Allen, Andrew J. Wagner. Differential evolution of tumor heterogeneity in leiomyosarcomas and liposarcomas suggested by genomic profiling. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4819. doi:10.1158/1538-7445.AM2015-4819
Unfavourable effects of medically indicated oral anticoagulants on survival in idiopathic pulmonary fibrosis: methodological concerns
Authors: Leticia Kawano-Dourado, Fernando Zampieri, Alexandre Biasi Cavalcanti, Lucas Petri Damiani, Ronaldo Adib Kairalla
Journal: European Respiratory Journal (2016)

We read with great interest the article by Kreuter et al. [1] describing the unfavourable effects of anticoagulants in a pooled analysis of idiopathic pulmonary fibrosis (IPF) patients randomised to the placebo arm from the ASCEND (Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis) and CAPACITY (Clinical Studies Assessing Pirfenidone in Idiopathic Pulmonary Fibrosis: Research of Efficacy and Safety Outcomes) trials [2, 3]. In this pooled analysis, IPF anticoagulant users differed significantly from nonusers in almost every important baseline characteristic: anticoagulant users were older (age 71.1±6.8 versus 66.9±7.5 years, p=0.0025) and they also had a higher prevalence of cardiovascular disease (43.8% versus 25.8%, p=0.0259), chronic renal failure (9.4% versus 2.9%, p=0.0419), pulmonary embolism (15.6% versus 0.2%, p<0.0001), pulmonary hypertension (9.4% versus 2.7%, p=0.0324), atrial fibrillation (46.9% versus 2.4%, p=0.0001) and deep vein thrombosis (28.1% versus 1.4%, p<0.0001). Therefore, IPF anticoagulant users started off with an increased risk of death simply due to the higher prevalence of baseline cardiovascular comorbidities. The question whether medically indicated anticoagulants are harmful to IPF patients still remains unanswered <http://ow.ly/KU3Y302SEMQ>
TCT-57 Impact of Lesion Length on 1-year Outcomes of Absorb Bioresorbable Vascular Scaffolds
Authors: Rony Lahoud, Stephen Ellis, Dean Kereiakes, Runlin Gao, Takeshi Kimura, Yoshinobu Onuma, Wai-Fung Cheong, Jennifer Jones, Zhengyang Zhang, Robert McGreevy
Journal: Journal of the American College of Cardiology (2016)
Women are unaware of pregnancy risks linked with sodium valproate
Authors: Zosia Kmietowicz
Journal: BMJ (2016)

Doctors are being asked to make sure that women and girls with epilepsy know about the risks of taking sodium valproate during pregnancy, after a survey found that half of those questioned were unaware that it could harm the fetus.

The charities Epilepsy Action, Epilepsy Society, and Young Epilepsy conducted a survey earlier this year, in conjunction with the Medicines and Healthcare Products Regulatory Agency (MHRA), of 2788 women aged 16 to 50 with epilepsy.

It found that one in five (20%) women currently taking sodium …
DISECCIÓN SUBMUCOSA ENDOSCÓPICA. ¿ES PRECISO INICIARSE EN EL USO DE ESTA TÉCNICA EN LESIONES DE ESTÓMAGO?
Authors: M Rullán, L Casanova, C Saldaña, A Zúñiga, D Oyón, S López, J Carrascosa, D Ruiz-Clavijo, E Albéniz, JJ Vila
Journal: Endoscopy (2016)

Introducción: En Japón se recomienda comenzar la curva de aprendizaje de la disección submucosa endoscópica (DSE) por lesiones antrales. La ESGE (European Society of Gastrointestinal Endoscopy) introduce la posibilidad de iniciarse con lesiones rectales de manera segura y eficaz.
Abstract 1778: Selectively targeting the DNA-binding domain of the androgen receptor as a prospective therapy for prostate cancer
Authors: Kush Dalal, Mani Roshan-Moniri, Aishwariya Sharma, Huifang Li, Fuqiang Ban, Mohamed D. Hassona, Michael Hsing, Kriti Singh, Eric LeBlanc, Scott Dehm, Emma Tomlinson Guns, Artem Cherkasov, Paul S. Rennie
Journal: Cancer Research (2015)

Abstract The androgen receptor (AR) is a hormone-activated transcription factor implicated in the development and progression of prostate cancer. The AR contains an N-terminal domain (NTD), followed by DNA binding (DBD) and ligand-binding (LBD) domains. Upon binding of androgens to the LBD, the AR moves into the nucleus where it interacts with target genes via the conserved AR-DBD. Prostate cancer treatment involves the use of small-molecules to block androgen production or to compete with androgens for binding to the AR-LBD. Drug-resistance occurs when LBD mutations render small-molecule treatment ineffective or when constitutively active AR splice variants, lacking the LBD, become overexpressed. We recently identified a surface pocket on the AR-DBD that may serve as an alternative drug-target site. The DBD-specific, small molecule compounds presented here block transcriptional activity of full-length and splice variant AR forms across multiple cell lines and show no cross-reactivity with related steroid nuclear receptors. The inhibition is lost when residues in the binding pocket are mutated or when the AR-DBD is replaced with a different DNA binding domain. Biophysical techniques were used to explore the interaction of these compounds with the purified, recombinant DBD protein. Gene expression analysis demonstrated the down-regulation of AR target genes following compound treatment, without any obvious expression signature associated with toxicity. The compounds affected DNA binding in vitro and also blocked interactions of the AR with chromatin inside the nucleus. Finally, the lead compound suppressed the growth of LNCaP tumor xenografts and was accompanied by down-regulation of AR target genes, such as PSA. These results suggest a mechanism whereby our developed inhibitory compounds interfere with DNA binding by the AR, potentially leading to effective treatment of advanced, castration-resistant prostate cancers. Citation Format: Kush Dalal, Mani Roshan-Moniri, Aishwariya Sharma, Huifang Li, Fuqiang Ban, Mohamed D. Hassona, Michael Hsing, Kriti Singh, Eric LeBlanc, Scott Dehm, Emma Tomlinson Guns, Artem Cherkasov, Paul S. Rennie. Selectively targeting the DNA-binding domain of the androgen receptor as a prospective therapy for prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1778. doi:10.1158/1538-7445.AM2015-1778
Prognostic value of hemoglobin in natural killer cell lymphoma
Authors: J. Xiao, T. Lin, Y. Cao, X. Fu, C. Guo, L. Zhai, Z. Guan
Journal: Journal of Clinical Oncology (2006)

17557 Background: Natural Killer (NK) cell lymphoma is a group of increasingly recognized but poorly defined disease entities. This study investigated its clinical features and prognostic factors for southern China population. Methods: Patients with pathologically confirmed NK cell lymphoma in one center since 1999 to 2004 were included. Central histological and immunohistochemical review was undertaken to every case. The major study endpoint was overall survival. Survival curves were estimated by the Kaplan-Meier method. Detailed clinical, pathological and laboratory data were included in univariate analysis and statistically significant factors in univariate analysis were then included in multivariate analysis. Results: Totally 64 eligible patients were identified. Of these, 59 patients were extranodal NK cell lymphoma nasal type, 3 patients were aggressive NK cell lymphoma and 2 patients were blastic NK cell lymphoma. From the basic analysis, 47% of the patients had stage I disease, 42% were stage II, 11% were stage III or IV. B-symptoms were present in 39%. 73% of these patients had International Prognostic Index (IPI) 0 or 1. Before treatment, 25% complicated with anemia. As to the therapy, 38% received chemotherapy alone, 3% received radiotherapy alone and 59% received a multidisciplinary therapy. After initial therapy, 59% achieved CR, 22% achieved PR and 19% were refractory disease. With a median follow-up duration of 20 months, the median overall survival was 28 months (95% CI: 10, 45). Hb lower than 110 g/l before treatment was statistically significant in multivariate analysis (p = 0.031). Presenting B-symptoms and ECOG PS score higher than 1 were also independent prognostic factors (P = 0.001 and 0.006 respectively). Conclusions: The outcome of patients with NK cell lymphoma was poor even for Stage I or II cases. Our data suggested Hemoglobin &lt; 110 g/l had more prognostic value than IPI and Ann Arbor staging system for NK cell lymphoma in southern China, but it needs further confirmation. No significant financial relationships to disclose.
Bayesian Brains without Probabilities
Authors: Adam N. Sanborn, Nick Chater
Journal: Trends in Cognitive Sciences (2016)

TrendsBayesian models in cognitive science and artificial intelligence operate over domains such as vision, motor control and language processing by sampling from vastly complex probability distributions.Such models cannot, and typically do not need to, calculate explicit probabilities.Sampling naturally generates a variety of systematic probabilistic reasoning errors on elementary probability problems, which are observed in experiments with people.Thus, it is possible to reconcile probabilistic models of cognitive and brain function with the human struggle to master even the most elementary explicit probabilistic reasoning.AbstractBayesian explanations have swept through cognitive science over the past two decades, from intuitive physics and causal learning, to perception, motor control and language. Yet people flounder with even the simplest probability questions. What explains this apparent paradox? How can a supposedly Bayesian brain reason so poorly with probabilities? In this paper, we propose a direct and perhaps unexpected answer: that Bayesian brains need not represent or calculate probabilities at all and are, indeed, poorly adapted to do so. Instead, the brain is a Bayesian sampler. Only with infinite samples does a Bayesian sampler conform to the laws of probability; with finite samples it systematically generates classic probabilistic reasoning errors, including the unpacking effect, base-rate neglect, and the conjunction fallacy.
UTILIDAD CLÍNICA DE LA ELASTOGRAFÍA MEDIANTE ECOENDOSCOPIA PARA EL DIAGNÓSTICO DE PANCREATITIS CRÓNICA
Authors: M Masachs Peracaula, M Abu-Suboh Abadia, J Armengol Bertroli, A Benages Curell, MD Castillo Cejas, D Sihuay, J Guevara, MJ Pascasio, J Dot Bach, JR Armengol Miró
Journal: Endoscopy (2016)

La ecoendoscopia (EUS) es una técnica de referencia para el estudio del páncreas. La elastografía mediante EUS proporciona información adicional acerca de la rigidez del tejido. La utilidad clínica de la elastografía para el diagnóstico de la pancreatitis crónica se ha evaluado en pocos estudios. El objetivo de este estudio es evaluar la información proporcionada por la elastografía cualitativa y cuantitativa para el diagnóstico de la pancreatitis crónica..
PREVALENCIA Y CARACTERÍSTICAS CLÍNICAS DEL “MISSED GASTRIC CANCER”
Authors: B Arau, X Andújar, Y Zabana, C Ferrer, F Fernández-Bañares, M Rosinach, M Aceituno, J Espinós, M Esteve, C Loras
Journal: Endoscopy (2016)

Introducción: La videogastroscopia (VGC) es muy efectiva para diagnosticar cáncer gástrico (CG). Se estima que un 10% de CG pasan desapercibidos y no son diagnosticados (MGC, “missed gastric cancer”).
MCPH1 (BRIT1) and outcome to erlotinib in non-small cell lung cancer (NSCLC) patients (p) harboring EGFR mutations.
Authors: M. Rosario Garcia-Campelo, Miquel Taron, Susana Benlloch, Jose Javier Sanchez, Carlota Costa, Ana Gimenez Capitan, Jordi Bertran-Alamillo, Clara Mayo, Miguel Angel Molina-Vila, Margarita Majem, Teresa Moran, Bartomeu Massuti, Carlos Camps, Dolores Isla, Manuel Cobo, Sara Cros, Laia Capdevila, Enric Carcereny Costa, Santiago Viteri Ramirez, Rafael Rosell
Journal: Journal of Clinical Oncology (2012)

e18131 Background: Progression-free survival (PFS) in EGFR-mutant NSCLC p treated with erlotinib can range from a few months (m) to more than two years, but genetic influences on the duration of response remain unclear. The cytotoxic effect of erlotinib has been related to several proteins that regulate DNA damage response (eg, BRCA1, BRCA2). MCPH1 contains 3 BRCT domains which are conserved in important molecules involved in DNA damage signaling, including BRCA1, MDC1 and 53BP1. MCPH1 binds to BRCA2 and regulates the localization of BRCA2 and Rad51 at sites of DNA damage. MCPH1 also regulates the ATP-dependent SWI-SNF chromatin remodeling complex during DNA repair. Methods: We used the NanoString nCounter gene expression system, which captures and counts individual mRNA transcripts, to analyze the expression of 44 selected genes, many of which are involved in DNA damage response, in 55 erlotinib-treated NSCLC p. We identified MCPH1 and correlated expression levels with clinical outcomes. Results: p characteristics: 16 males, 39 females (70.9%); 39 never-smokers (70.9%), 12 former smokers, 4 current smokers; 34 with EGFR deletion in exon 19 (61.8%), 21 with L858R mutation (38.2%). PFS was not reached for patients with high MCPH1, while it was 19 m for those with intermediate levels and 9 m for those with low levels (P=0.01). Median survival was 31 m for p with high levels, not reached for p with intermediate levels and 17 m for p with low levels (P=0.004). Conclusions: The enhanced effect of erlotinib in the presence of elevated MCPH1 could be due to the fact that MCPH1 can interfere with the function of MDC1 and 53BP1. The role of MCPH1 merits validation as a predictive marker of erlotinib response.
Noninvasive CT-Derived FFR Based on Structural and Fluid Analysis
Authors: Brian S. Ko, James D. Cameron, Ravi K. Munnur, Dennis T.L. Wong, Yasuko Fujisawa, Takuya Sakaguchi, Kenji Hirohata, Jacqui Hislop-Jambrich, Shinichiro Fujimoto, Kazuhisa Takamura, Marcus Crossett, Michael Leung, Ahilan Kuganesan, Yuvaraj Malaiapan, Arthur Nasis, John Troupis, Ian T. Meredith, Sujith K. Seneviratne
Journal: JACC. Cardiovascular imaging (2016)
Single-Ventricle Outcomes After Neonatal Palliation of Severe Ebstein Anomaly With Modified Starnes Procedure
Authors: S. Ram Kumar, Grace Kung, Nathan Noh, Novel Castillo, Brian Fagan, Winfield J. Wells, Vaughn A. Starnes
Journal: Circulation (2016)

We have previously shown that neonates in profound cardiogenic shock caused by a severe Ebstein anomaly can be successfully salvaged with fenestrated right ventricular exclusion and systemic to pulmonary shunt (modified Starnes procedure). The long-term outcome of single-ventricle management in these patients is not known.We retrospectively reviewed the records of patients who underwent neonatal Starnes procedure between 1989 and 2015. Patient demographics, clinical variables, and outcome data were collected.Twenty-seven patients (13, 48% boys) underwent the Starnes procedure at 7 (5-9) days of life. All were intubated and on prostaglandin, 24 (89%) were inotrope dependent, and 22 (81%) had no antegrade flow from the right ventricle. Three patients underwent nonfenestrated right ventricular exclusion, 2 (67%) of whom died. Of the remaining 24, 3 (13%) died during the same hospitalization. The 22 neonatal survivors have been followed for 7 (6-8) years: 1 patient is awaiting a Glenn procedure; 1 died after undergoing a Glenn procedure; and the remaining 20 patients have successfully undergone Fontan completion. Their indexed pulmonary vascular resistance was 1.8 (1.2-2.3) W/m2, and mean pulmonary pressure was 12 (9-18) mm Hg. At last follow-up, 1 patient had died, and the remaining patients had normal left ventricular function, and all but 1 have New York Heart Association class I symptoms. Two patients have required pacemaker implantation, whereas the rest are in sinus rhythm. Survival for the entire cohort at 1, 5, and 10 years is 81±4%, 81±5%, and 76±3%, respectively, whereas for those with fenestrated right ventricular exclusion, survival at 1, 5, and 10 years is 87±2%, 87±2%, and 81±4%, respectively.Long-term single-ventricle outcomes among neonatal survivors of the modified Starnes procedure are excellent. There is reliable remodeling of the excluded right ventricle and good function of the left ventricle.
TCT-470 Two Year Clinical Results after Deployment of the Abluminal Sirolimus Coated Bio-Engineered (COMBO) Stent in a Thousand Patient All-Comers Registry
Authors: Deborah Kalkman, Pier Woudstra, Peter Den Heijer, Ian Brian Alexander Menown, Andrejs Erglis, Harry Suryapranata, Karin Arkenbout, Andres Iñiguez, Arnoud van't Hof, Philippe Muller, Jan Tijssen, Robbert de Winter
Journal: Journal of the American College of Cardiology (2016)
TCT-617 Cost Effectiveness Following Treatment Initiation of Stroke Reduction Strategies in Non-Valvular Atrial Fibrillation: Warfarin vs NOACs vs Left Atrial Appendage Closure
Authors: Vivek Reddy, Ronald Akehurst, Meghan Gavaghan, Stacey Amorosi, David Holmes
Journal: Journal of the American College of Cardiology (2016)