tbuckley/cabot-search huggingface dataset:
Abstract 336: A 14-3-3 Mode-1 Binding Motif Promotes Gap Junction Internalization During Acute Cardiac Ischemia
Authors: James W Smyth, Jose M Sanchez, Samy Lamouille, Ting-Ting Hong, Jacob M Vogan, Robin M Shaw
Journal: Circulation Research (2013)

During each heartbeat, robust cell-cell electrical coupling via connexin 43 (Cx43) gap junctions allows billions of individual cardiomyocytes to contract in synchrony. Cx43 turns over rapidly, and altered Cx43 trafficking during disease contributes to the arrhythmias of sudden cardiac death. The overall phosphorylation status of the Cx43 protein is known to regulate gap junction coupling, but the role of many residue specific phosphorylation events remains unknown. One such residue, Ser373, forms a mode-1 14-3-3 binding motif upon phosphorylation. Given that 14-3-3 proteins are known to regulate protein trafficking, we hypothesized a role for Cx43 Ser373 phosphorylation in regulation of Cx43 gap junction coupling. Using Langendorff-perfused mouse hearts we find robust phosphorylation of Cx43 at Ser373 and Ser368 after 30 min of no-flow ischemia. In human cell lines, a S373A mutation ablated Cx43/14-3-3 complexing and 35 S pulse-chase revealed Cx43 S373A also experiences a longer half-life than wild-type Cx43. Previous reports have implicated phosphorylation of Cx43 Ser368 in PKC mediated Cx43 internalization. We find that upon activation of PKC, the Cx43 S373A mutant undergoes lower and more transient levels of phosphorylation at Ser368 than wild-type Cx43. Consistent with these data, siRNA-mediated ablation of 14-3-3 expression results in enlargement of gap junction plaque formation at cell-cell borders. In conclusion, we propose that phosphorylation of Cx43 Ser373 results in 14-3-3 binding which promotes and maintains phosphorylation of Cx43 Ser368 and the subsequent internalization of gap junction channels. These results identify for the first time a specific role for 14-3-3 proteins in regulation of Cx43 internalization during acute ischemia and contribute to the development of therapies aimed at preserving or enhancing gap junction coupling in the heart.
CD66 identifies a neutrophil-specific epitope within the hematopoietic system that is expressed by members of the carcinoembryonic antigen family of adhesion molecules
Authors: SM Watt, G Sala-Newby, T Hoang, DJ Gilmore, F Grunert, G Nagel, SJ Murdoch, E Tchilian, ES Lennox, H Waldmann
Journal: Blood (1991)
Alpha 1 acid glycoprotein (AGP) binds to STIS71 and alters its tissue distribution and intracellul4r concentrations
Authors: Carlo Gambacorti-Passerini, Massimo Zucchetti, Loredana Cleris, Francesca Rossi, Enrico Pogliani, Gianmarco Corneov, Franca Formelli, Maurizio D'Lncalci
Journal: Blood (2000)
Safety and Efficacy of Dasatinib Treatment Change for Patients Previosly Treated with Imatinib with Late Warning Response. Results from the Phase II, Open, Multicenter Dasapost Study
Authors: Valentín García-Gutierrez, Felipe Casado, Fermín Sánchez-Guijo, Rosa M. Ayala, Concepcion Boque, Blanca Xicoy, Isabel Montero, Cesar Soto, Raquel De Paz, Joaquin Martinez-Lopez, Juan Luis Steegmann
Journal: Blood (2016)
Tissue microenvironment dictates the fate and tumor-suppressive function of type 3 ILCs
Authors: Kathrin Nussbaum, Sara H. Burkhard, Isabel Ohs, Florian Mair, Christoph S.N. Klose, Sebastian J. Arnold, Andreas Diefenbach, Sonia Tugues, Burkhard Becher
Journal: The Journal of Experimental Medicine (2017)

Innate lymphoid cells (ILCs) have been classified into "functional subsets" according to their transcription factor and cytokine profiles. Although cytokines, such as IL-12 and IL-23, have been shown to shape plasticity of ILCs, little is known about how the tissue microenvironment influences the plasticity, phenotype, and function of these cells. Here, we show clearly demarcated tissue specifications of Rorc-dependent ILCs across lymphoid and nonlymphoid organs. Although intestinal Rorc fate map-positive (Rorcfm+) ILCs show a clear ILC3 phenotype, lymphoid tissue-derived Rorcfm+ ILCs acquire an natural killer (NK) cell/ILC1-like phenotype. By adoptively transferring Rorcfm+ ILCs into recipient mice, we show that ILCs distribute among various organs and phenotypically adapt to the tissue environment they invade. When investigating their functional properties, we found that only lymphoid-tissue resident Rorcfm+ ILCs can suppress tumor growth, whereas intestinal Rorcfm- ILC1s or NK cells fail to inhibit tumor progression. We thus propose that the tissue microenvironment, combined with ontogeny, provides the specific function, whereas the phenotype is insufficient to predict the functional properties of ILCs.
Safety of Converting From Tetrabenazine to Deutetrabenazine for the Treatment of Chorea
Authors: Samuel Frank, David Stamler, Elise Kayson, Daniel O. Claassen, Amy Colcher, Charles Davis, Andrew Duker, Shirley Eberly, Lawrence Elmer, Erin Furr-Stimming, Mark Gudesblatt, Christine Hunter, Joseph Jankovic, Sandra K. Kostyk, Rajeev Kumar, Clement Loy, William Mallonee, David Oakes, Burton L. Scott, Victor Sung, Jody Goldstein, Christina Vaughan, Claudia M. Testa
Journal: JAMA Neurology (2017)

Tetrabenazine is efficacious for chorea control; however, tolerability concerns exist. Deutetrabenazine, a novel molecule that reduces chorea, was well tolerated in a double-blind, placebo-controlled study.To evaluate the safety and explore the efficacy of conversion from tetrabenazine to deutetrabenazine in patients with chorea associated with Huntington disease (HD).In this ongoing, open-label, single-arm study that started on December 21, 2013, 37 patients at 13 Huntington Study Group sites in the United States and Australia who were taking stable doses of tetrabenazine that provided a therapeutic benefit were switched overnight to deutetrabenazine therapy. After week 1, the deutetrabenazine dose was titrated on a weekly basis for optimal chorea control.Deutetrabenazine administration at a dosage thought to provide comparable systemic exposure to the active metabolites of the prior, stable tetrabenazine regimen.Safety measures included adverse events (AEs), clinical laboratory tests, vital signs, electrocardiograms, and validated scales. Changes in the Unified Huntington's Disease Rating Scale total maximal chorea score and total motor score were efficacy end points.Of the 53 patients with HD screened for the study, 37 ambulatory patients with manifest HD (mean [SD] age, 52.4 [11.5] years; 22 [59%] male and 15 [41%] female; 36 white [97.3%]) were enrolled. Deutetrabenazine was generally well tolerated, with low rates of neuropsychiatric AEs. Safety scales did not reveal subclinical toxicity with deutetrabenazine treatment. Rates of dose reduction or suspension attributable to AEs were also low. Chorea control, as measured by the total maximal chorea score, was maintained at week 1 and significantly improved at week 8 (mean [SD] change from baseline, 2.1 [3.2]; P < .001).In patients with chorea, overnight conversion to deutetrabenazine therapy provided a favorable safety profile and effectively maintained chorea control.
Expansion of Myeloid Immune Suppressor Cells in Tumor-bearing Host Directly Promotes Tumor Angiogenesis, Tumor Growth, and Metastasis
Authors: P. Lin, Laura DeBusk, Jianhua Huang, Lynn Matrisian, Hal Moses, David Carbone, Li Yang
Journal: Clinical Cancer Research (2007)

PL02-02  Myeloid immune suppressor cells (MISCs), of myeloid macrophage/dendritic cell lineage, are significantly over-produced in the bone marrow and spleens of tumor-bearing mice as well as in peripheral blood of cancer patients. Interestingly, VEGF, the potent angiogenic factor and produced in most solid tumors, induces MISC production in vivo. In mice they express CD11b, a marker for myeloid cells of the macrophage lineage, and a marker for granulocytes, Gr-1. MISCs have been demonstrated to be immune suppressive since the 1980s. In this report, we demonstrate a novel tumor-promoting role of myeloid immune suppressor cells. These cells constitute 5% of total cells in solid tumors. Tumor cells coinjected with MISCs exhibited increased vascularization and decreased necrosis, as well as enhanced tumor growth. These immune cells produce high levels of MMP9. Deletion of MMP9 in these cells completely abolishes their tumor-promoting ability. MISCs were also found to directly incorporate into tumor endothelium. Consistent with this observation, MISCs acquire endothelial cell properties in tumor microenvironment and proangiogenic culture conditions. Furthermore, MISCs promote tumor metastasis through enhanced invasion. MISCs infiltrate into the invasive front with enhanced production and function of MMPs. Mice with 4T1 tumors co-injected with MISCs had significantly higher recurrent tumors at the injection site following surgical removal. 4T1 cells co-cultured with MISCs showed significantly increased invasion in vitro. Treatment with an MMP inhibitor significantly attenuated this process, suggesting a strong role of MISCs in tumor cell invasion through MMPs. In summary, MISCs are over-produced in tumor-bearing hosts, they can be re-programmed in multiple ways to promote tumor progression including angiogenesis, tumor growth and metastasis. Cellular and molecular targeting of MISC production should not only improve host immunosurveillance but also inhibit tumor metastasis, having the effect of “killing two birds with one stone.”
Prospective study of the impact of neuro-oncology multi-disciplinary meetings on clinical decision making.
Authors: Malaka Ameratunga, Dorothea Miller, Wayne Ng, Lawrence Cher, Augusto Gonzalvo, Morikatsu Wada, Hui Kong Gan
Journal: Journal of Clinical Oncology (2017)

e13512 Background: Multi-disciplinary team (MDT) meetings are considered essential to quality cancer care. For some malignancies, MDTs have been associated with improved outcomes, but data is limited for their utility in neuro-oncology. The aim of this study was to prospectively describe the MDT at our institution and evaluate its impact on clinical management. Methods: All cases discussed over three months at the Austin Health neuro-oncology MDT were prospectively evaluated. Cases were discussed amongst the treating team and a provisional plan (PP) and reason for discussion (RFD) was documented preceding the MDT. The PP was recorded as: surgery, radiation, chemoradiation, further diagnostic tests, surveillance and other. Patient specific clinical data was captured prospectively, with further pathological and radiological information captured during the MDT. Subsequently, the MDT reached a consensus decision, which was recorded. High impact decisions (HID) were those in which a substantial modification to the PP was made. Subsequent data regarding patient adherence to the MDT plan was recorded. Results: Over the period 79 cases were discussed at the MDT. Twenty-seven (34%) cases were female, 52 (66%) were male. The median age was 53. Six patients were discussed more than once. Forty-three cases were new diagnoses. Forty-two cases were primary brain tumours, twenty-five were metastatic solid organ malignancies. Thirty-four per cent of cases had HID. On chi-square analysis, the RFD was not statistically associated with HID (p = 0.28), nor was the primary versus recurrent setting (p = 0.80) however, the nature of the PP was (p = 0.023). Adherence data was collected for 95% (75) of cases. Adherence to the MDT plan occurred 90% (67) of cases. For cases of non-adherence, six out of eight (75%) were due to patient choice. Conclusions: A significant proportion of treatment modifications are made following discussion at the neuro-oncology MDT. The nature of the provisional treatment plan may influence which cases are likely to have a change in management determined in the MDT. MDT recommendations are broadly adhered to, and in cases of non-adherence, are largely due to patient factors.
Abstract 045: Highly-reactive Lipid Aldehydes Are Downstream Mediators Of Oxidant-induced Spontaneous Ca Waves
Authors: Hyun Seok Hwang, Sean Davies, Bjorn C Knollmann
Journal: Circulation Research (2013)

Background: Reactive oxygen species (ROS) can activate ryanodine receptor (RyR2) Ca release channel and generate arrhythmogenic Ca waves (SCWs) in myocytes. ROS also cause lipid peroxidation in cell membranes that produce highly-reactive g-ketoaldehydes (IsoK), which can react immediately with proteins (RyR2) and accumulate in ischemic human heart. We previously found that specific IsoK scavengers reduce infarct size and prevent ventricular arrhythmia in an MI mouse model, suggesting a biological role of IsoK in oxidant heart injury. We hypothesize that IsoK mediate in part the ROS-induced SCW in myocytes. Methods: We compared the effect of H 2 O 2 , synthetic IsoK, the specific IsoK scavenger (SA, salicylamine), its inactive homolog (4-SA, 4-OH-salicylamine), and the ROS scavenger (MPG, 2-mercaptopropionyl glycine) in field-stimulated mouse ventricular myocytes loaded with Fura-2AM. Results: Thirty min exposure to H 2 O 2 (10μM) or IsoK (1μM) both generated SCWs (H 2 O 2 37%, IsoK 37%, p&lt;0.05 vs.vehicle, VEH). MPG, (100μM, 60 min) prevented H 2 O 2 -induced SCWs, but had no effect on IsoK-induced SCWs ( Fig.A ). Pre-treatment with SA (8 μM, 60 min) significantly reduced H 2 O 2 -induced SCWs, whereas 4-SA had no effect on H 2 O 2 -induced SCWs (%SCWs, H 2 O 2 ; 53%, SA+H 2 O 2 ; 27%*, 4-SA+H 2 O 2 ; 56%. *p&lt;0.05 vs. VEH, Fig. B ). In the absence of H 2 O 2 , MPG, SA, or 4-SA had no significant effect on Ca handling in myocytes. Conclusion: IsoK directly activate SCWs independent of ROS production in myocytes. Specific IsoK scavengers inhibit 50% of ROS-induced SCWs. Hence, our data suggested that IsoK are biologically-relevant downstream mediators of oxidant-induced RyR2 dysfunction.
ARHGAP18 Protects Against Thoracic Aortic Aneurysm Formation by Mitigating the Synthetic and Proinflammatory Smooth Muscle Cell Phenotype
Authors: Renjing Liu, Lisa Lo, Angelina J. Lay, Yang Zhao, Ka Ka Ting, Elizabeth N. Robertson, Andrew G. Sherrah, Sorour Jarrah, Haibo Li, Zhaoxiong Zhou, Brett D. Hambly, David R. Richmond, Richmond W. Jeremy, Paul G. Bannon, Mathew A. Vadas, Jennifer R. Gamble
Journal: Circulation Research (2017)

Thoracic aortic aneurysm (TAA) is a potentially lethal condition, which can affect individuals of all ages. TAA may be complicated by the sudden onset of life-threatening dissection or rupture. The underlying mechanisms leading to TAA formation, particularly in the nonsyndromal idiopathic group of patients, are not well understood. Thus, identification of new genes and targets that are involved in TAA pathogenesis are required to help prevent and reverse the disease phenotype.Here we explore the role of ARHGAP18, a novel Rho GAP expressed by smooth muscle cells (SMCs), in the pathogenesis of TAA.Using human and mouse aortic samples, we report that ARHGAP18 levels were significantly reduced in the SMC layer of aortic aneurysms. Arhgap18 global knockout (Arhgap18-/-) mice exhibited a highly synthetic, proteolytic, and proinflammatory smooth muscle phenotype under basal conditions and when challenged with angiotensin II, developed TAA with increased frequency and severity compared with littermate controls. Chromatin immunoprecipitation studies revealed this phenotype is partly associated with strong enrichment of H3K4me3 and depletion of H3K27me3 at the MMP2 and TNF-α promoters in Arhgap18-deficient SMC. We further show that TAA formation in the Arhgap18-/- mice is associated with loss of Akt activation. The abnormal SMC phenotype observed in the Arhgap18-/- mice can be partially rescued by pharmacological treatment with the mTORC1 inhibitor rapamycin, which reduces the synthetic and proinflammatory phenotype of Arhgap18-deficient SMC.We have identified ARHGAP18 as a novel protective gene against TAA formation and define an additional target for the future development of treatments to limit TAA pathogenesis.
Abstract 370: MicroRNA-19b Contributes to Cardiac Fibrosis
Authors: Ping Chen, Dongchao Lv, Jiahong Xu, Qiulian Zhou, Qi Sun, Junjie Xiao
Journal: Circulation Research (2015)

Fibrosis is one of the most important characteristics of cardiac remodeling during heart failure. The accumulation of extracellular matrix (ECM) within myocardium is the major feature of cardiac fibrosis. microRNA (miR)-19b, a key functional member of miR-19-72 cluster family, has been suggested to be involved in aging-induced heart failure through regulating ECM-related proteins, such as connective tissue growth factor (CTGF), thrombospondin-1 (TSP-1), collagen-1A1, and collagen-3A1. In the current study, we aimed to investigate the role of miR-19b in cardiac fibroblast function and ECM production using neonatal rat cardiac fibroblasts in primary culture. We found that overexpression of miR-19b increased, while inhibition of miR-19b decreased the proliferation and migration of cardiac fibroblasts, using Cell Counting Kit-8 (CCK-8) (0.660±0.019 vs 0.720±0.014 in nc-mimic and miR-19b mimic, 0.506±0.009 vs 0.454±0.008 in nc-inhibitor and miR-19b inhibitor, respectively), EdU incorporation assay (0.059±0.002 vs 0.096±0.006 in nc-mimic and miR-19b mimic, 0.059±0.006 vs 0.040±0.003 in nc-inhibitor and miR-19b inhibitor, respectively), and wound healing assay (0.528±0.024 vs 0.896±0.027 in nc-mimic and miR-19b mimic,0.520±0.028 vs 0.174±0.019 in nc-inhibitor and miR-19b inhibitor, respectively), respectively. Meanwhile, the inhibition of miR-19b downregulated the mRNA levels of α-SMA (0.556±0.048 vs 1.038±0.137 in nc-inhibitor and miR-19b inhibitor, respectively) and collagen-1 (1.023±0.116 vs 0.551±0.033 in nc-inhibitor and miR-19b inhibitor, respectively) in cardiac fibroblasts, indicating a reduction in fibroblast activation and ECM production via miR-19b inhibition. Furthermore, we found that PTEN was negatively regulated by miR-19b in cardiac fibroblasts using western blot analysis. PTEN, a well-known tumor-suppressor gene, has been known to inhibit cell proliferation and migration. However, it remains to be further clarified whether PTEN could mediate the effect of miR-19b in the proliferation, migration and activation of fibroblasts. These data might provide important evidence suggesting that miR-19b could be a potential therapeutic target for cardiac fibrosis.
Core Quality and Outcome Measures for Pediatric Health
Authors: William Gardner, Kelly J. Kelleher
Journal: JAMA Pediatrics (2017)

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 Pediatrics 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 Pediatrics journal
Overestimating the Benefit of Cancer Drugs—Reply
Authors: Sebastian Salas-Vega, Elias Mossialos
Journal: JAMA Oncology (2017)

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 Oncology 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 Oncology journal
Allogeneic hematopoietic cell transplantation for high-risk CLL: 10-year follow-up of the GCLLSG CLL3X trial
Authors: Isabelle Krämer, Stephan Stilgenbauer, Sascha Dietrich, Sebastian Böttcher, Matthias Zeis, Michael Stadler, Jörg Bittenbring, Lutz Uharek, Christof Scheid, Ute Hegenbart, Anthony Ho, Michael Hallek, Michael Kneba, Norbert Schmitz, Hartmut Döhner, Peter Dreger
Journal: Blood (2017)
Factors influencing HER2 positivity in breast cancer according to statistical modeling and data mining techniques based on a real-world national database: HER-France.
Authors: Marie-Pierre Chenard, Eric Anger, Marie-Helene Bizollon, Jerome Chetritt, Francesco Bruno Cutuli, Jean Kapfer, Magali Lacroix, Catherine Lefebvre, Eve Lefort, Gaetan mac Grogan, Julien Palasse, Thomas Petit, Bruno Poulet, Vincent Rouleau, Emmanuel Watkin, Dominique Fetique, David Pau, Jean-Pierre Bellocq
Journal: Journal of Clinical Oncology (2016)

e12086 Background: HER-France is a national database collecting information on HER2 status in invasive breast cancer supplied by 124 French pathology labs (FPL). It is conducted by the French Association for Quality Control in Histopathology (AFAQAP) since October 2011. Its goal is to follow the national HER2 rate and its change over time. An analysis of this database was carried in October 2015 on 105,717 records to search for factors associated with HER2 positivity. Methods: To identify these factors, multivariate regression models were applied, as well as supervised and unsupervised Data Mining techniques such as Bayesian Networks and Decision trees were used to represent dependencies between tumor characteristics and HER2 positivity. HER2 status was determined by immunohistochemistry and in situ hybridization using ASCO/CAP 2013 guidelines. To avoid bias due to adverse pre-analytic conditions, only results on Core-Biopsies (CB) are presented hereafter. Results: Out of 105,717 records, 45,785 (43.3%) CB were analyzed. 41,586 (90.8%) CB were evaluable for HER2 status and 4,976 (12.0%) were HER2+. Factors influencing HER2 positivity were No Special Type histologic subtype (OR=2.27, 95%CI [1.89-2.77]), high histologic grade (OR=4.71, 95%CI [3.86-5.76]), negative or low hormonal receptor status (OR=1.85, 95%CI [1.67-2.04]), and higher Ki67 index (OR=3.06, 95%CI [2.72-3.44]). Bayesian Network confirmed the importance of these parameters, providing thresholds linked to high HER2 positivity rates, as shown in table below. Conclusions: HER-France is a nationwide database showing 12.0% of HER2+ on breast cancer CB between 2011 and 2015. Histological subtype, grade and ER-PR status as reported in the German database study (Ruschoff et al.), but also Ki67 are factors influencing HER2 positivity. In the future, these results should be integrated to develop new HER-France functionalities in order to allow FPL to compare their actual HER2 rate to the expected HER2 rate based on these factors. Number of cases % of HER2 positivity Histological Grade 3 4,448 26.7% ER positive cells ≤78% 6,052 25.8% Ki67 ≥ 18% 10,020 21.7% PR positive cells ≤25% 9,717 20.5%