tbuckley/cabot-search huggingface dataset:
Abstract 5132: Pooled shRNA screens conducted <i>in vitro</i> and <i>in vivo</i> identify genes that are essential for the growth and/or survival of human tumor cells
Authors: Tara M. Young, Elizabeth Pasnikowski, Padmini Sahoo, Gavin Thurston, Christopher Daly
Journal: Cancer Research (2012)

Abstract Identification of novel drug targets is a major challenge in cancer research. While numerous studies have identified genes that are mutated and/or amplified in cancers, the functional significance of most of these genetic alterations remains unknown. To directly identify genes that are required for the growth of human tumor cells, and that could potentially be targets for therapeutic monoclonal antibodies, we employed a custom shRNA library containing ∼13,000 shRNAs targeting 3,210 genes (∼4 shRNAs per gene) that encode cell surface or secreted proteins. Cultured tumor cells were infected with the virally-packaged shRNA library such that each shRNA (and an associated molecular barcode) was integrated into ∼200 cells. Cells that expressed shRNAs that target essential genes were progressively depleted from the population upon in vitro passage or following implantation into mice, resulting in decreased representation of those shRNAs/barcodes versus reference samples. In vitro screens were conducted in 3 colorectal cancer cell lines (HCT116, DLD1 and Colo320DM) and in NCI-H1975 lung cancer cells. About 1-3% of the genes in the library were identified as essential for tumor cell growth and/or survival in vitro. Importantly, these genes included positive controls such as PCNA that were included in the library to validate the screening procedure, as well as components of pathways that are known to control cell growth such as IGF-1R, Wnt9a, sonic hedgehog and RON. In vivo screens were performed with HCT116 and NCI-H1975 cells by implanting cells into mice immediately following shRNA integration. Representation of shRNAs versus the reference sample was assessed in small tumors (∼100 mm3) and in large tumors (1000 mm3). While we observed very few hits in small tumors, the number of hits in large tumors was greater than that observed in vitro (e.g., ∼3-fold higher for HCT116), suggesting that tumor growth in vivo is dependent on a larger set of genes than is cell growth in vitro. Interestingly, the genes that were uniquely essential in tumors versus in vitro included several that are involved in cell/cell adhesion (e.g., cadherin 24, claudin 3) and cell signaling (epidermal growth factor receptor). In summary, our shRNA screens focusing on secreted and cell surface targets have identified genes that may be essential for tumor growth, including many genes that have not previously been implicated in this process. Upon further validation, these genes could potentially serve as novel targets for therapeutic antibodies in 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 5132. doi:1538-7445.AM2012-5132
Sensorimotor learning in structures “upstream” from the cerebellum
Authors: Paul van Donkelaar
Journal: Behavioral and Brain Sciences (1996)

Thach, following the Marr-Albus theory, suggests that the cerebellum contributes to sensorimotor learning through a process of context-response linkage. However, perceptual learning studies demonstrate that the context itself is subject to adaptive modifications and recent evidence has shown that motor responses derived from such perceptions display appropriate changes which may be quite independent of cerebellar processing. [HOUR et al.; SMITH; THACH]
Abstract 2772: Inhibition of EGFR activity reduces AML cell survival via inhibition of downstream Akt and Erk signaling pathways.
Authors: Ellen R. Scheepers, Kim R. Kampen, Eveline SJM de Bont
Journal: Cancer Research (2013)

Abstract Epidermal growth factor receptor (EGFR) inhibitor erlotinib, has been shown to induce complete remission of acute myeloid leukemia (AML) in two patients with concurrent lung cancer, suggesting a prominent role for EGFR in AML. However, EGFR expression analysis in AML is poorly defined and the role of EGFR in AML is still unclear. In this study, we determined the EGFR protein expression in different human AML cell lines and studied the impact of EGFR inhibition by canertinib on the AML cell survival, proliferation, apoptosis and their downstream signaling routes. Using flowcytometry, we have shown that total EGFR as well as the phosphorylated residue Tyr1068 is expressed in five out of the eight AML cell lines (range of 4.9-46.6% for total and phosphorylated EGFR). EGFR phosphorylation was found to be induced by EGF stimulation, which could be prevented by canertinib treatment, showing functional activity and specificity of the EGFR phosphorylation site. Canertinib was shown to decrease the AML cell survival sufficiently (at a median IC50 of 6.2 μM, range: 0.9 - 15.2 μM canertinib in n=8 AML cell lines) as measured by WST-1 assays. The lower cell survival was the net result of lower numbers of mitotic phospho-histone H3 positive cells and an increase in the number of Annexin V positive cells. Immunoblot analysis revealed that canertinib treatment (5uM) reduced the phosphorylation of Akt and Erk intracellular proteins downstream of the EGFR signaling pathway in AML cells. Long-term canertinib treatment (5uM) showed that downstream targets were re-activated after 24 hours, which suggest kinomic reprogramming by alternative escape mechanisms compensating for the loss of EGFR activity. These findings suggest encouraging possibilities for targeting EGFR as a therapeutic strategy in AML. Future studies are necessary to determine the exact mechanism through which EGFR activity might contribute to AML progression, relapses as well as to interact with possible escape mechanisms of AML cells. Citation Format: Ellen R. Scheepers, Kim R. Kampen, Eveline SJM de Bont. Inhibition of EGFR activity reduces AML cell survival via inhibition of downstream Akt and Erk signaling pathways. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2772. doi:10.1158/1538-7445.AM2013-2772
PROLAPSE VOLUME TO PROLAPSE HEIGHT RATIO FOR DIFFERENTIATING BARLOW’S DISEASE FROM FIBROELASTIC DEFICIENCY
Authors: Nobuyuki Kagiyama, Hayashida Akihiro, Misako Toki, Takao Morikawa, Tomonori Miki, Yasuhiko Kamata, Minako Ohara, Atsushi Hirohata, Keizo Yamamoto, Kiyoshi Yoshida
Journal: Journal of the American College of Cardiology (2016)
INCREASED FDG UPTAKE IN REPERFUSED CANINE MYOCARDIUM REPRESENTS SUSTAINED ANAEROBIC METABOLISM
Authors: M. Schwaiger, R. Neese, L. Araujo, M. C. Fishbein, J. Wisneski, M. E. Phelps, H. R. Schelbert, E. Gertz
Journal: Clinical Nuclear Medicine (1986)

Schwaiger, M.; Neese, R.; Araujo, L.; Fishbein, M. C.; Wisneski, J.; Phelps, M. E.; Schelbert, H. R.; Gertz, E. Author Information
CS-37 * DUAL FUNCTIONS OF EFEMP1 IN MALIGNANT GLIOMA IN RESPECT TO REGULATION OF EGFR AND NOTCH SIGNALING PATHWAYS
Authors: Y.-H. Zhou, Y. Hu, C. Ke, N. Ru, L. Yu, E. Siegel, M. Linskey
Journal: Neuro-Oncology (2014)

EFEMP1 exerts both tumor suppressive and oncogenic effects in glioma. EFEMP1's binding to EGFR accounts for its suppression of the intracranial (i.c.) tumorigenicity of glioma cells expressing high levels of EGFR. This finding is consistent with an overall favorable prognosis value of EFEMP1 expression in gliomas, specifically high EGFR-expression ones. We also found that in gliomas without EGFR overexpression, heightened levels of EFEMP1 expression were associated with unfavorable patient outcomes in prognosis models. To delineate the cell context-dependent function of EFEMP1 in glioma, we compared the effect of EFEMP1 to EGFR and NOCTH signaling activities in different glioma cell lines/primary cultures and their derived subpopulation lines. The results showed a common effect of EFEMP1 on blocking EGFR signaling, but variations on NOTCH signaling. In U87 glioma cell line, EFEMP1 blocked EGFR while activated NOTCH, with overall suppression of i.c. tumorigenicity. In U251 glioma cell line, EFEMP1 blocked EGFR but no effect on NOTCH signaling, and overall suppression of i.c. tumorigenicity. In U251-derived subculture (U251-NS) which was enriched with stem-like tumor initiating cells where EGFR expression level was low, EFEMP1 up-regulated NOTCH1, HES1, and HEY1 gene expressions. The effect of EFEMP1 to U251-NS i.c. tumorigenicity was contradictory. It changes the effect of tumor promoting to tumor suppressing by increasing inoculum size. With increase of inoculum size in i.c. xenograft model or exposing cells to serum in in vitro culture, there was an increase of chromosome 7 copy score (total chromosome 7 number per cell in xenografts/cell culture) and increase of EGFR expression. EFEMP1 changed pro-invasion function to anti-growth, hence reduced the alteration on equilibrium of tumor heterogeneity in responding to changes of tumor microenvironment. In conclusion, the effect of EFEMP1 up or down-regulation in malignant glioma needs to be studied in respect to the status of EGFR and NOTCH signaling activities.
APPLICATION OF PEDIATRIC APPROPRIATE USE CRITERIA FOR OUTPATIENT EVALUATION OF SYNCOPE BY PEDIATRIC CARDIOLOGISTS
Authors: Heather M. Phelps, Michael Kelleman, Courtney McCracken, Oscar Benavidez, Robert Campbell, Pamela Douglas, Benjamin Eidem, Wyman Lai, Leo Lopez, Kenan Stern, Rory Weiner, Liz Welch, Ritu Sachdeva
Journal: Journal of the American College of Cardiology (2016)
Cryoballoon or Radiofrequency Ablation for Paroxysmal Atrial Fibrillation
Authors: Karl-Heinz Kuck, Josep Brugada, Alexander Fürnkranz, Andreas Metzner, Feifan Ouyang, K.R. Julian Chun, Arif Elvan, Thomas Arentz, Kurt Bestehorn, Stuart J. Pocock, Jean-Paul Albenque, Claudio Tondo
Journal: New England Journal of Medicine (2016)

Current guidelines recommend pulmonary-vein isolation by means of catheter ablation as treatment for drug-refractory paroxysmal atrial fibrillation. Radiofrequency ablation is the most common method, and cryoballoon ablation is the second most frequently used technology.We conducted a multicenter, randomized trial to determine whether cryoballoon ablation was noninferior to radiofrequency ablation in symptomatic patients with drug-refractory paroxysmal atrial fibrillation. The primary efficacy end point in a time-to-event analysis was the first documented clinical failure (recurrence of atrial fibrillation, occurrence of atrial flutter or atrial tachycardia, use of antiarrhythmic drugs, or repeat ablation) following a 90-day period after the index ablation. The noninferiority margin was prespecified as a hazard ratio of 1.43. The primary safety end point was a composite of death, cerebrovascular events, or serious treatment-related adverse events.A total of 762 patients underwent randomization (378 assigned to cryoballoon ablation and 384 assigned to radiofrequency ablation). The mean duration of follow-up was 1.5 years. The primary efficacy end point occurred in 138 patients in the cryoballoon group and in 143 in the radiofrequency group (1-year Kaplan-Meier event rate estimates, 34.6% and 35.9%, respectively; hazard ratio, 0.96; 95% confidence interval [CI], 0.76 to 1.22; P<0.001 for noninferiority). The primary safety end point occurred in 40 patients in the cryoballoon group and in 51 patients in the radiofrequency group (1-year Kaplan-Meier event rate estimates, 10.2% and 12.8%, respectively; hazard ratio, 0.78; 95% CI, 0.52 to 1.18; P=0.24).In this randomized trial, cryoballoon ablation was noninferior to radiofrequency ablation with respect to efficacy for the treatment of patients with drug-refractory paroxysmal atrial fibrillation, and there was no significant difference between the two methods with regard to overall safety. (Funded by Medtronic; FIRE AND ICE ClinicalTrials.gov number, NCT01490814.).
Abstract 1952: Deregulated microRNA expression in the progression of salivary gland cancer.
Authors: Hao Zheng, Alan Kiang, Selena Z. Kuo, Elham Rahimy, Jessica Wang-Rodriguez, Weg M. Ongkeko
Journal: Cancer Research (2013)

Abstract Salivary gland cancer constitutes one of the five main subsets of cancer in the head and neck region. Nonresectable malignant tumors demonstrate a low 20-year survival rate due to radioresistance and a high propensity for metastasis. The molecular mechanisms underlying pathogenesis of salivary cancer remains poorly elucidated, and thus necessitates further investigation. MicroRNAs (miRNA) are small noncoding RNAs that are predicted to regulate up to 30% of protein-encoding genes. Signature miRNA expression profiles have been identified in various malignancies, implicating miRNAs in the progression of human cancer. In order to better understand the role of miRNAs in the progression of salivary cancer, we profiled the miRNA expression levels of normal salivary tissue, benign salivary tumor, and salivary cancer. A total of 17 formalin-fixed paraffin-embedded salivary tissues, including 4 normal, 4 pleomorphic adenoma (PA), 3 squamous cell carcinoma (SCC), 3 mucoepidermoid carcinoma (ME) and 3 adenocarcinoma (AC), were collected and the endogenous expression of 95 miRNAs was analyzed by microarray. A large number of miRNAs were observed to be aberrantly expressed and generally down-regulated in salivary cancer and salivary tumor tissues with respect to normal salivary gland tissues. An unsupervised clustering and a student t-test were performed with a threshold p-value less than 0.05, resulting in the identification of 22 miRNAs differentially expressed at a statistically significant level. Eight candidate miRNAs were selected and further validated by RT-qPCR. The results suggest three miRNAs in SCC (miR-200a, let-7-family, and miR-192) and three miRNAs in AC (miR-107, miR-15b and miR-200a) to be highly involved in the carcinogenetic process of salivary cancers. Furthermore, the up-regulated expression pattern of miR-203 is indicative of a tumorigenetic function in salivary tumors. Interestingly, miR-200b was found to be consistently and significantly down regulated (p=0.01, 19.03 fold decrease) in the three types of salivary cancer under investigation. Recent studies have implicated miR-200b in EMT and invasion in cancer cells by directly targeting E-cadherin transcriptional repressors. The miRNAs identified in this study may serve as potential biomarkers and targets for future miRNA based therapy. Citation Format: Hao Zheng, Alan Kiang, Selena Z. Kuo, Elham Rahimy, Jessica Wang-Rodriguez, Weg M. Ongkeko. Deregulated microRNA expression in the progression of salivary gland cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1952. doi:10.1158/1538-7445.AM2013-1952
Bullous pemphigoid and dipeptidyl peptidase IV inhibitors: a case-noncase study in the French Pharmacovigilance Database
Authors: J. Béné, G. Moulis, I. Bennani, M. Auffret, P. Coupe, S. Babai, D. Hillaire-Buys, J. Micallef, S. Gautier
Journal: British Journal of Dermatology (2016)

Inhibitors of dipeptidyl peptidase (DPP)‐IV have been suspected in the onset of bullous pemphigoid for several years now. However, comparative studies assessing the link between DPP‐IV inhibitor exposure and bullous pemphigoid have not yet been performed. To detect, from the French Pharmacovigilance Database (FPVD), a signal of risk of bullous pemphigoid during DPP‐IV inhibitor exposure by comparative study. All spontaneous reports of DPP‐IV inhibitor‐related bullous pemphigoid recorded in the FPVD between April 2008 and August 2014 were described. We conducted disproportionality analyses (case–noncase method) to assess the link between DPP‐IV inhibitors and bullous pemphigoid, calculating reporting odds ratios (RORs). We also compared DPP‐IV inhibitor‐induced bullous pemphigoid reports rated per million defined daily doses dispensed during the study period. Among 217 331 spontaneous adverse drug reaction reports registered in the FPVD, 1297 involved DPP‐IV inhibitors. Among these observations, 42 were bullous pemphigoid (vildagliptin, n = 31; sitagliptin, n = 10; saxagliptin, n = 1). The ROR for pooled DPP‐IV inhibitors was 67·5 [95% confidence interval (CI) 47·1–96·9]. Disproportionality was also observed for each DPP‐IV inhibitor: vildagliptin (ROR 225·3, 95% CI 148·9–340·9), sitagliptin (ROR 17·0, 95% CI 8·9–32·5) and saxagliptin (ROR 16·5, 95% CI 2·3–119·1). Analyses adjusted on dispensing data led to similar results. These data confirm a strong signal for an increased risk of bullous pemphigoid during DPP‐IV inhibitor exposure. This adverse drug reaction is observed for each DPP‐IV inhibitor, suggesting a class effect. The signal was higher with vildagliptin than with the other DPP‐IV inhibitors.
INCREASED LIPID-RICH PLAQUE BUT NOT GREATER PLAQUE BURDEN IN MYOCARDIAL INFARCTION LESIONS: THE COLOR REGISTRY
Authors: Cheolmin Lee, Akiko Maehara, Mitsuaki Matsumura, Yamamoto Myong Hwa, Annapoorna Kini, David Rizik, Eric Powers, Priti Shah, James Muller, Jordan Andrews, Gregg Stone, Gary Mintz, Stephen Nicholls, Giora Weisz
Journal: Journal of the American College of Cardiology (2016)
Western Europe Unifying to Tackle Varied Cancer Problems
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Western Europe Unifying to Tackle Varied Cancer Problems Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 11, 3 June 1992, Pages 836–838, https://doi.org/10.1093/jnci/84.11.836 Published: 03 June 1992
Abstract LB-307: Hyaluronan deposition correlates with poor survival in pancreatic cancer
Authors: Clifford J. Whatcott, Ping Jiang, April Watanabe, Galen Hostetter, Chengcheng Hu, Michael Shepard, Gregory Frost, Daniel Von Hoff, Haiyong Han
Journal: Cancer Research (2011)

Abstract Hyaluronan (HA) is an extracellular matrix component that plays an important role in a diverse range of cellular processes including proliferation, tissue hydration, cell motility, inflammation, angiogenesis, and malignancy. Increased HA deposition is a characteristic of many desmoplastic tumors. High HA levels have been correlated with poor prognosis in some cancer types, including gastric, colorectal, breast, ovarian, and bladder cancers. Considering the high desmoplastic stromal content of pancreatic tumors, we hypothesized that high HA levels may contribute to poor prognosis or survival in pancreatic cancer. Utilizing a biotinylated HA binding protein-based staining method in a tissue microarray constructed from resected pancreatic tumor tissues, we assessed HA-specific staining in 43 pancreatic ductal adenocarcinoma samples for which patient survival had been followed for more than eight years. We observed HA staining primarily in the peritumoral, or stromal, compartment of the tumor tissue samples. 100% of the patient tumors stained positive in at least some fraction of the tissue area (stroma) for HA. The staining was scored according to the percentage area of HA-positivity, relative to total tissue area. We observed low (&amp;lt;40%) and high (≥40%) levels of stromal HA in 11 and 32 patient samples, respectively. We tested our hypothesis with the log-rank test and found that the survival rate was significantly lower among patients with high HA (P&amp;lt;0.05). The median survival among those patients with high HA was 299 days, and 738 days for those with low HA (the difference in median survival between the two patient groups is 439 days). These results suggest that HA levels in pancreatic adenocarcinoma patients may be predictive of survival. Because HA functions in maintaining high tumoral interstitial fluid pressure, resulting in vascular compression and limited tumor-drug access, our results also suggest that HA may serve as a potential therapeutic target in pancreatic cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-307. doi:10.1158/1538-7445.AM2011-LB-307
Abstract 2068: A genome-wide siRNA screen reveals various modulators of the IRE1-XBP-1 signaling branch of the unfolded protein response
Authors: Jing Zhang, Alice Banh, Priya Jayachandran, Roy Wollman, David E. Solow-Codero, Tobias Meyer, Quynh-Thu Le, Albert C. Koong
Journal: Cancer Research (2011)

Abstract The unfolded protein response (UPR) is an essential cellular mechanism orchestrating endoplasmic reticulum (ER) homeostasis under various cytotoxic stresses. Dysregulation of the UPR signaling pathways is linked to multiple human diseases, including cancer. The inositol requiring kinase 1 (IRE1)-X-box binding protein 1 (XBP-1) pathway is the most evolutionarily conserved signaling branch of the UPR. When activated, the endoribonuclease activity of the IRE1 cleaves the XBP-1 mRNA and generates a spliced form of XBP-1 which transcriptionally regulates cell metabolism, proliferation, survival and apoptosis. Here, we employed a genome-wide siRNA screen to systematically identify genes modulating the IRE1-XBP-1 signaling pathway of the UPR. We induced cellular ER stress with bortezomib, a proteasome inhibitor, and monitored the expression of XBP-1-luciferase fusion protein in which luciferase is fused in-frame with the spliced form of XBP-1. We identified over 100 of genes whose downregulation results in inhibition of bortezomib-induced XBP-1 splicing. These genes include diverse subsets of proteins that are involved in mRNA processing, transcription, cell cycle regulation and cell proliferation and differentiation. Furthermore, the screen reveals a connection of several oncogenes and tumor suppressors, such as Myc, Akt and cyclin K, to the UPR, underlining the important role of the IRE1-XBP-1 signaling branch in human cancers. In summary, our data suggest that the UPR is tightly connected with previously unappreciated pathways regulating various cellular processes. 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 2068. doi:10.1158/1538-7445.AM2011-2068
APRENDIZAJE DISECCION SUBMUCOSA ENDOSCÓPICA ESOFÁGICA CIRCUNFERENCIAL
Authors: A Herreros De Tejada, M Hernández, JL Calleja, M Santos, P Matallanos, E Blázquez, J Santiago, J De La Revilla, L Abreu
Journal: Endoscopy (2014)

Introducción: En casos de neoplasia esofágica superficial extensa, la disección endoscópica submucosa esofágica circunferencial (DSE-CE) es un tratamiento adecuado. La DSE-CE representa un desafío técnico y un riesgo significativo de estenosis (70 – 90%).
A memorable patient: When reality defies delusion
Authors: B. McCann
Journal: BMJ (2001)

In a former existence I was training in general practice in the midlands of Ireland, where my psychiatric attachment included home visits with the community psychiatric nurse, Liam. Liam had worked in the area for nearly 40 years. On the day in question our destination was the remote and beautiful Glen of Aherlow, where two farming brothers with schizophrenia lived in a small isolated cottage. The brothers were in their 60s, and Liam had known them since his arrival in the glen.

As Liam drove over the Galtee mountains, I was flicking through the brothers' hospital notes. A recurring and prominent delusional feature was noted in John's chart—that his brother, Jim, regularly appeared on the television …