tbuckley/cabot-search huggingface dataset:
Abstract 1956: A subset of prostate cancer cells with loss of MST1 expression confers resistance to castration through YAP1-AR interactions
Authors: Bekir Cinar, Gamze Kuser Abali, Michael Lewis, Colm Morrissey, Isla Garraway
Journal: Cancer Research (2015)

Abstract MST1 is a core kinase component of the Hippo tumor suppressor pathway. YAP1 is a transcriptional cofactor and a prominent nuclear effector of the Hippo signaling. YAP1 activation is linked to cancer promotion with poor prognosis. However, the role of MST1-YAP axis in prostate cancer (PC) progression remains unknown. Here we isolated MST1 high and MST1 low/- expressing cell subsets from a well-characterized LNCaP PC cell model by employing novel method that utilizes an epigenetically regulated-MST1 promoter-driven GFP reporter combined with FACS. We performed molecular and functional characterizations of these cells utilizing a wide variety of experimental approaches. We demonstrated that unlike MST1 high, MST1 low/- cells shared the features of cancer stem cells (CSCs) and epithelial-to-mesenchymal transition (EMT) phenotype, showed superior osteogenic abilities, and were resistant to androgen depletion and enzalutamide (ENZ), a potent inhibitor of androgen receptor (AR). Consistently, silencing of MST1 expression by siRNA recapitulated the above molecular and function behaviors of MST1 low/- cells. In addition, MST1 low/- cells showed superior invasive growth abilities in vitro and tumor-forming abilities with metastatic potentials in mice compared with those of MST1 high cells. Moreover, relative YAP1 expression and its nuclear localization were much higher in MST1 low/- cells than MST1 high cells. Likewise, YAP1 protein levels and its nuclear abundance were increased in PC clinical samples compared to non-cancerous counters. We further showed that YAP1 interacted with AR in an androgen-dependent manner in LNCaP cells, whereas the interactions between the two proteins were androgen-independent (AI) in C4-2 CRPC cells. Furthermore we found that unlike LNCaP, YAP1-AR interactions were resistant to ENZ exposure in C4-2 cells. Consistently, silencing of MST1 in LNCaP cells augmented AI interactions between YAP1 and AR proteins. Finally, the disruption of YAP1 signaling by RNAi and Verteporfin (VP) attenuated C4-2 cell growth and promoted apoptosis, accompanied with the attenuation of AR-dependent gene expression. In conclusion, our findings suggest that the Hippo-YAP1-AR signaling axis is one of the key mechanisms for metastatic PC progression and may represent as a promising therapeutic target for patients with the lethal disease. Note: This abstract was not presented at the meeting. Citation Format: Bekir Cinar, Gamze Kuser Abali, Michael Lewis, Colm Morrissey, Isla Garraway. A subset of prostate cancer cells with loss of MST1 expression confers resistance to castration through YAP1-AR interactions. [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 1956. doi:10.1158/1538-7445.AM2015-1956
Management of stage I and II nonsmall cell lung cancer
Authors: Fiona McDonald, Michèle De Waele, Lizza E. L. Hendriks, Corinne Faivre-Finn, Anne-Marie C. Dingemans, Paul E. Van Schil
Journal: European Respiratory Journal (2016)

The incidence of stage I and II nonsmall cell lung cancer is likely to increase with the ageing population and introduction of screening for high-risk individuals. Optimal management requires multidisciplinary collaboration. Local treatments include surgery and radiotherapy and these are currently combined with (neo)adjuvant chemotherapy in specific cases to improve long-term outcome. Targeted therapies and immunotherapy may also become important therapeutic modalities in this patient group. For resectable disease in patients with low cardiopulmonary risk, complete surgical resection with lobectomy remains the gold standard. Minimally invasive techniques, conservative and sublobar resections are suitable for a subset of patients. Data are emerging that radiotherapy, especially stereotactic body radiation therapy, is a valid alternative in compromised patients who are high-risk candidates for surgery. Whether this is also true for good surgical candidates remains to be evaluated in randomised trials. In specific subgroups adjuvant chemotherapy has been shown to prolong survival; however, patient selection remains important. Neoadjuvant chemotherapy may yield similar results as adjuvant chemotherapy. The role of targeted therapies and immunotherapy in early stage nonsmall cell lung cancer has not yet been determined and results of randomised trials are awaited.
40. Nuclease-Targeted Gene-Editing of FOXP3 in Primary T Cells Creates a Stable and Functional T reg Phenotype
Authors: Nicholas W. Hubbard, David Hagin, Karen M. Sommer, Yumei Song, Iram Khan, Andrew M. Scharenberg, David J. Rawlings, Troy R. Torgerson
Journal: Molecular Therapy (2016)

Reprogramming T cells to adopt regulatory T cell (Treg) functions represents a promising strategy for treating autoimmune disorders and graft-versus-host disease. The development and maintenance of Treg cells is dependent on FOXP3 expression, which in turn is tightly controlled through epigenetic modification of intronic conserved non-coding sequences (CNS) surrounding the first coding exon. Two major challenges associated with FOXP3 gene-transfer approaches for Treg reprogramming are: achieving adequately high FOXP3 expression, and avoiding eventual gene silencing. We devised two gene editing strategies with the goal of driving stable expression of FOXP3 in primary human T cells. Using a combination of TALEN-mediated gene disruption and adeno-associated-virus (AAV) delivered donor repair templates, we introduced either an MND promoter upstream of the first coding exon, or we deleted intronic CNS implicated in transcriptional silencing. The donor templates were also designed to co-express FOXP3 with either GFP or EGFRt (truncated Epidermal Growth Factor receptor), to allow tracking and purification of edited cells. Both strategies resulted in T cells stably expressing FOXP3 at high levels (~60 %). Introduction of the MND promoter resulted in the greatest levels of cellular FOXP3 expression (MFI), and these cells showed phenotypic and functional changes consistent with Treg cells, including: surface marker expression (CD25high, CD127low, CTLA4high, LAG3high), suppression of cytokine production (IL-2, IL-17 and IFN-γ), and resistance to Rapamycin. Edited cells also suppressed the proliferation of stimulated T cells in vitro, demonstrating their effective 'reprogramming' towards a Treg lineage. Thus, our gene modification strategy allowed us to over-ride (using the MND promoter) or modulate (by deleting CNS elements) endogenous FOXP3 regulatory mechanisms to enforce stable, long-term FOXP3 expression in T cells that were not previously committed to the Treg lineage. This approach, used alone or in combination with selection for disease-relevant TCR specificity or with delivery of a chimeric antigen receptor, is likely to be broadly applicable for producing stable, functionally active Tregs for a range of future clinical applications.
A Model of Canine Purkinje Cell Electrophysiology and Ca <sup>2+</sup> Cycling
Authors: Pan Li, Yoram Rudy
Journal: Circulation Research (2011)

Purkinje cells (Pcell) are characterized by different electrophysiological properties and Ca(2+) cycling processes than ventricular myocytes (Vcell) and are frequently involved in ventricular arrhythmias. Yet, the mechanistic basis for their arrhythmic vulnerability is not completely understood. The objectives were to: (1) characterize Pcell electrophysiology, Ca(2+) cycling, and their rate dependence; (2) investigate mechanisms underlying Pcell arrhythmogenicity; and compare Pcell and Vcell electrophysiology, Ca(2+) cycling, and arrhythmic properties. We developed a new mathematical model of Pcell. The Ca(2+) subsystem includes spatial organization and receptors distribution unique to Pcell. Results were: (1) in Pcell and Vcell, Na(+) accumulation via its augmentation of repolarizing I(NaK) dominates action potential duration adaptation and, in Pcell, I(NaL) contributes additional action potential duration shortening at short cycle length; (2) steep Pcell restitution is attributable to slow recovery of I(NaL); (3) biphasic Ca(2+) transients of Pcell reflect the delay between Ca(2+) release from junctional sarcoplasmic reticulum and corbular sarcoplasmic reticulum; (4) Pcell Ca(2+) alternans, unlike Vcell, can develop without inducing action potential alternans; (5) Pcell action potential alternans develops at a shorter cycle length than Vcell, with increased subcellular heterogeneity of Ca(2+) cycling attributable to refractoriness of Ca(2+) release from corbular sarcoplasmic reticulum and junctional sarcoplasmic reticulum; (6) greater Pcell vulnerability to delayed afterdepolarizations is attributable to higher sarcoplasmic reticulum Ca(2+) content and ionic currents that reduce excitation threshold and promote triggered activity; and (7) early after depolarizations generation in Pcell is mostly attributable to reactivation of I(NaL2), whereas I(CaL) plays this role in Vcell. Steeper rate dependence of action potential and Ca(2+) transients, central peripheral heterogeneity of Ca(2+) cycling, and distinct ion channel profile underlie greater arrhythmic vulnerability of Pcell compared to Vcell.
NEGATIVE INFLUENCE of IL8 and RANTES Ctyokines On CORD BLOOD CD133+ CELL SDF-1-CXCR4 Function
Authors: Nicholas J Greco, Mathew Lesnewski, Alex Wendling, Kalipraveena Iruku, Janina Ratajczak, Mariusz Z Ratajczak, Mary J. Laughlin
Journal: Blood (2010)
Cord Blood (CB) Extends Transplant Access to Racial and Ethnic Minorities: A Prospective Study of 309 Unrelated Searches in Patients with High-Risk Hematologic Malignancies
Authors: Sinda S. Lee, Andromachi Scaradavou, Rebecca M. Hawke, Kathleen A. Webb, Deborah S. Wells, Michelle Abboud, Esperanza B. Papadopoulos, Nancy A. Kernan, Juliet N. Barker
Journal: Blood (2008)
A Recommendation Against Serologic Screening for Genital Herpes Infection—What Now?
Authors: Edward W. Hook
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A Case of Chronic Myelomonocytic Leukemia Progressing from Dysplastic to Proliferative Phenotype after Acquisition of a RAS Point Mutation.
Authors: Clara Ricci, Francesco Onida, Elisa Fermo, Ermanna Rovida, Federica Servida, Agostino Cortelezzi, Giorgio Lambertenghi-Deliliers, Davide Soligo
Journal: Blood (2005)
Abstract 5137: IQGAP1, an ERK1/2 MAPK scaffold, is an oncogenic target in canine melanoma
Authors: Ashley Zehnder, Becky Lee, Poornima Neela, Paul Khavari
Journal: Cancer Research (2015)

Abstract BACKGROUND: Human cutaneous melanoma is primarily driven by activating mutations in Braf (60%) or Nras (20%). However, human oral melanoma harbors these mutations much less frequently. Similarly, canine oral mucosal melanomas have not been found to have activating Braf or Nras mutations. This makes them an ideal model to study alternative means of ERK1/2 MAPK pathway activation as these tumors are still reliant on MAPK signaling. We have previously studied IQGAP1 as a tumor specific ERK1/2 MAPK scaffold and shown that it is required for cancer progression. METHODS: In this study, we utilized canine oral melanoma cell lines obtained from the University of California-Davis. We examined the expression and localization of IQGAP1, a signaling scaffold that regulates oncogenic ERK1/2 MAPK signaling in human cancer, and validate it as an oncogenic target in the canine melanoma model. Using a CRISPR/Cas9 knockout of IQGAP1, we examined effects on downstream pathway activation. Additionally, we assayed proliferation of these cell lines when treated with a peptide that blocks the interaction between IQGAP1 and ERK1/2. RESULTS: We observed that canine IQGAP1 is expressed and localizes to a similar extent in human and canine melanoma by qPCR, Western blot and immunofluorescence. Deletion of IQGAP1 from two canine oral melanoma cell lines using CRISPR-Cas9 genome editing reduces MAPK pathway activation, similar to effects seen in human BrafV600E cell lines. Additionally, we demonstrated reduced proliferation when these cells are treated with the WW blocking peptide in-vitro. We are currently investigating the expression and localization of IQGAP1 in primary canine oral melanoma compared to normal oral mucosa. CONCLUSION: Building on the above findings to explore alternative MAPK signaling in melanoma using the canine melanoma model may yield novel therapeutic strategies and novel means to target canine and human tumors that are resistant to current Braf and MEK targeted therapies. Citation Format: Ashley Zehnder, Becky Lee, Poornima Neela, Paul Khavari. IQGAP1, an ERK1/2 MAPK scaffold, is an oncogenic target in canine melanoma. [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 5137. doi:10.1158/1538-7445.AM2015-5137
Demodectic Frost of the Ear
Authors: Matthew M. Wallace, Darren J. Guffey, Barbara B. Wilson
Journal: JAMA Dermatology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Need to travel for urologic care: The impact of insurance.
Authors: Matthew Mossanen, Kenn Dhartha, Sarah Holt, Jonathan L. Wright, Jonathan D. Harper, John L. Gore
Journal: Journal of Clinical Oncology (2015)

396 Background: We sought to examine the impact of the Affordable Care Act on access to subspecialty services, such as urologic care, through evaluating the need to travel by insurance status for index urologic procedures. Methods: We accessed the Comprehensive Hospital Abstract Reporting System from 2011-2012. Patients were identified using billing claims and ICD-9 codes. Procedures analyzed were: radical cystectomy (RC), radical prostatectomy (RP), transurethral prostate resection, shockwave lithotripsy, nephrectomy, percutaneous nephrolithotomy (PCNL), retroperitoneal lymph node dissection (RPLND), and pyeloplasty. Patients were categorized as Medicaid, Medicare, private/Health Maintenance Organization, or other (i.e. charity care). Hospital service areas (HSAs, where the majority of local patients were hospitalized), and hospital referral regions (HRR, where most patients received tertiary care) were identified. Chi squared analysis and multivariate logistic regression were performed. Results: We identified 600 patients with Medicaid, 3,806 patients with Medicare, 4,998 patients with private insurance, and 554 with other. 13.3% of Medicaid patients undergoing RC left their HRR versus 29.9% for Medicare and 39.8% for private insurance (Chi squared p &lt; 0.05). We found similar trends for RP (10.8% of Medicaid traveled outside of their HRR vs. 19.5% for Medicare and 24.6% for private, p &lt; 0.05) and PCNL (21.9% of patients with private insurance traveled outside of HRR vs. 12% with Medicare and 17.2% with Medicaid, p &lt; 0.05). On multivariate analysis, (adjusting for race, age, and comorbidity) private insurance had higher odds of leaving their HRR (OR = 1.4, CI 1.1 – 1.8, p&lt; 0.002). Non-white patients (OR = 0.66, 0.54 – 0.81, p &lt;0.001), those with increased comorbidities (OR = 0.95, CI 0.91 - .99, p&lt;0.04), and older patients (p &lt; 0.001) are less likely to travel outside of their HRR. Conclusions: Patients undergoing complex urologic procedures like RC, RP, and PCNL are more likely to travel outside of their HRR if they have private insurance, potentially reflecting increased capacity to access healthcare resources based on income. Patients of older age and with greater comorbidities may be less likely to travel outside of their HRR to obtain urologic care.
Busulfan Conditioning In Sheep In Utero Transplantation Confers Engraftment Potential on Human Hematopoietic Stem Cells as Efficiently as HoxB4 Transduction.
Authors: Shigeo Masuda, Tomoyuki Abe, Satoshi Hayashi, Yujiro Tanaka, Hiroshi Ban, Makoto Inoue, Mamoru Hasegawa, Yoshikazu Nagao, Yutaka Hanazono
Journal: Blood (2010)
Combined Immunochemotherapy with Rituximab Improves Overall Survival in Patients with Follicular and Mantle Cell Lymphoma: Updated Meta-Analysis Results.
Authors: Holger Schulz, Julia Bohlius, Nicole Skoetz, Sven Trelle, Marcel Reiser, Thilo Kober, Guido Schwarzer, Michael Herold, Martin Dreyling, Andreas Engert
Journal: Blood (2006)
Family care, visiting policies, ICU performance, and efficiency in resource use: insights from the ORCHESTRA study
Authors: Marcio Soares, Ulysses V. A. Silva, Walter S. Homena, Guilherme C. Fernandes, Ana Paula P. De Moraes, Leonardo Brauer, Mariza F. Lima, Fernando V. De Marco, Fernando A. Bozza, Jorge I. F. Salluh
Journal: Intensive Care Medicine (2016)
Abstract 19334: Management and Outcomes of Acute Retrograde Type A Aortic Dissection: Insights From the International Registry of Acute Aortic Dissection
Authors: Foeke J Nauta, Joon Bum Kim, Himanshu J Patel, Mark D Peterson, Hans-Henning Eckstein, Lori D Conklin, Ali Khoynezhad, Marek P Ehrlich, Marco Di Eusanio, Alessandro Della Corte, Daniel G Montgomery, Eric M Isselbacher, Kim A Eagle, Christoph A Nienaber, Thoralf M Sundt, Santi Trimarchi
Journal: Circulation (2015)

Background: Presentations and outcomes of acute aortic dissection (AD) with an entry tear in the ascending aorta may differ from retrograde dissection with an entry tear in the descending aorta. However, guidelines recommend urgent surgical repair for both entities. Methods and Results: All patients with AD enrolled in the International Registry of Acute Aortic Dissection (IRAD) between 1996 and 2014 were analyzed. We identified 99 patients (67 men; 63.2±14.0 years) with an entry tear in the descending aorta and retrograde extension into the arch or ascending aorta. Overall, independent predictors of retrograde type A AD were increasing age(OR 1.0; 95% CI, 1.0 to 1.0; P=0.004), history of cocaine abuse (OR 4.9; 95% CI, 1.7 to 13.6; P=0.003), back pain at presentation (OR 2.1; 95% CI, 1.3 to 3.3; P=0.002), and non-white race (OR 0.4; 95% CI, 0.2 to 0.6; P&lt;0.001). During initial hospitalization, 44 of these patients were managed medically (MED), 33 with open surgery(SURG) and 22with endovascular therapy (ENDO). Patients in the SURG group presented with larger ascending aortic diameters than MED and ENDO patients (P=0.04). The majority of the MED (72.7%) and ENDO (86.4%) patients had AD extension confined to zone 1 (proximal arch, P&lt;0.001), whereas most of the SURG patients (71.8%) presented with AD extension into zone 0 (proximal to the innominate artery, P&lt;0.001). Early (30-day or in-hospital) mortality rates of the MED, SURG and ENDO groups were 9.1%, 18.2%, and 13.6%, respectively (P=0.51), with 5-year survival of 86.7%, 80.0%, and 90.9%, respectively (mean follow-up, 3.3 years, log rank P=0.67). A trend of favorable early mortality was observed in patients with retrograde extension till zone 1 (8.6%) versus into zone 0 (18.6%, P=0.14).Early mortality of patients with retrograde type A AD (12.9%) was lower than those with type A AD (20.0%, P=0.001), while 5-year survival was similar (86.8% and 89.5%, respectively, mean follow-up, 3.0 years, log rank P=0.96). Conclusion: There is a subset of patients with acute retrograde type A AD who can be managed non-operatively with acceptable short and long-term results. This implies that a selective approach may be reasonable, particularly among those with proximal extension limited to the arch distal to the innominate artery.
232. Generalized Entropy Based Clonal Diversity Estimation of TCR Repertoire
Authors: Saira Afzal, Shahzad Ahmad, Richard Gabriel, Eliana Ruggiero, Christof von Kalle, Manfred Schmidt, Raffaele Fronza
Journal: Molecular Therapy (2016)

In depth study of T-cell receptor (TCR) repertoire, specifically clonal expansion of T cells and diversity of repertoire, can provide invaluable information in various health and diseases states including infection, cancer and genetic disorders etc. Currently, Shannon and Simpson diversity indices used to estimate TCR clonality have certain limitations. These indices are biased either towards total number of different TCR receptor types (richness) or distribution of each clonal type (evenness). We introduced here a new framework for accurate and precise quantification of clonal diversity of TCR cell population that overcomes shortcomings of already available indices. Our concept is based on the generalized form of entropy known as Rényi numbers and two components of diversity, richness and evenness. Based on the Rényi equation, we can prove that at a specific richness value the highest possible evenness obtained cannot go beyond the stated richness value. Plotting richness versus evenness helps to define maximal theoretical polyclonality and monoclonality regions and diversity of sample can be measured by estimating distances of sample from these theoretical bounds. We have validated our method on in-silico data sets and TCR repertoire study. We conclude that our idea of clonal plane and diversity index measurement provides more reliable and robust estimation of immune population diversity. It can prove to be a useful tool for quantitative characterization of TCR repertoire in immunological studies.
P1251 : Hepatitis B and C: Knowledge, attitudes and preventive practices of the Greek general adult population. Preliminary results of the Greek national health examination survey “Hprolipsis”
Authors: A. Karakosta, V. Sypsa, G. Papatheodoridis, G. Vourli, O. Anagnostou, M. Kantzanou, M. Gavana, A. Vantarakis, G. Chlouverakis, P. Voulgari, Y. Alamanos, G. Rachiotis, G. Trypsianis, G. Touloumi
Journal: Journal of Hepatology (2015)