tbuckley/cabot-search huggingface dataset:
Abstract 3580: Acetaldehyde and drug hypersensitivities of Fanconi anemia defects: Implications for cancer initiation, prevention, and therapy.
Authors: Soma Ghosh, Surojit Sur, Sashidhar R. Yerram, Carlo Rago, Anil K. Bhunia, M. Zulfiquer Hossain, Bogdan C. Paun, Yunzhao R. Ren, Christine A. Iacobuzio-Donahue, Nilofer A. Azad, Scott E. Kern
Journal: Cancer Research (2013)

Abstract Studies of cells harboring Fanconi anemia (FA) pathway defects have aided clinical understanding of inherited cancer risks and therapeutic strategies. Here, we observed a novel and large (27X) hypersensitivity of BRCA2- and PALB2-null genotypes to the epidemiologically important ethanol metabolite, acetaldehyde. This prominent acetaldehyde sensitivity may hold evolutionary and clinical significance. Interrogation of a novel panel of cells engineered to be null for various FA genes also revealed two classes of chemical hypersensitivities: the shared and divergent phenotypes. Prominent chemical hypersensitivities to various interstrand crosslinking (ICL) agents in vitro (melphalan, mitomycin C, and cisplatin), to γ-radiation in vitro, and to mitomycin C in vivo were essentially similar among the tested genotypes. A large divergence of responsiveness existed, however, between the cell lines when using the PARP inhibitor KU0058948, the topoisomerase II inhibitor etoposide, and acetaldehyde. These results indicate that, toward some agents, not all FA defects are necessarily equivalent; this divergence among phenotypes may dissect functions differing among FA genes and may presage differing clinical and epidemiological implications. We additionally present the first engineered PALB2-null human cancer cells. The results suggest new applications in cancer epidemiology, prevention, and targeted therapy. Citation Format: Soma Ghosh, Surojit Sur, Sashidhar R. Yerram, Carlo Rago, Anil K. Bhunia, M. Zulfiquer Hossain, Bogdan C. Paun, Yunzhao R. Ren, Christine A. Iacobuzio-Donahue, Nilofer A. Azad, Scott E. Kern. Acetaldehyde and drug hypersensitivities of Fanconi anemia defects: Implications for cancer initiation, prevention, and therapy. [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 3580. doi:10.1158/1538-7445.AM2013-3580
Abstract 5076: Identification and anti-angiogenic effects of small molecule inhibitors of TEM8.
Authors: Lorna Cryan, Marinya Roznik, Aaron McBride, Robert D'Amato, Kenneth Christensen, Michael S. Rogers
Journal: Cancer Research (2013)

Abstract Tumor endothelial marker 8 (TEM8) is a gene upregulated on colonic tumor endothelium compared to quiescent normal endothelium. Inhibition of TEM8 using antibodies potently inhibits the growth of a variety of tumor types in mice. This inhibition of tumor growth is accompanied by a reduction in microvessel density within the tumors. Thus, TEM8 appears to represent a tumor specific endothelial marker that has a functional role in tumor angiogenesis. TEM8 is also a receptor for anthrax toxin. In the current study, we used chemical libraries to identify small molecule inhibitors of TEM8 that may have efficacy as inhibitors of tumor angiogenesis and anthrax toxin. We conducted a fluorescence resonance energy transfer (FRET) based screen of over 270,000 small molecules in order to identify molecules that inhibit the interaction of TEM8 with its well-known ligand anthrax protective antigen (PA). We describe here the identification and anti-angiogenic effects of small molecules that bind to TEM8. From the initial screen 280 molecules inhibited TEM8/PA interaction by greater than 50%. A secondary screen involved the elucidation of IC50 values for these 280 compounds as inhibitors of the TEM8/PA interaction. Twelve compounds had measurable IC50s in the micromolar range. The anti-angiogenic effects of these compounds were studied in vitro. Of the 12 compounds tested in a human microvascular endothelial cell (HMVEC) proliferation assay, 3 compounds significantly inhibited endothelial cell proliferation after 24 hours (P &amp;lt;0.05), and 5 compounds significantly inhibited proliferation at 72 hours (P &amp;lt;0.05). None of the compounds exhibited measurable cytotoxicity. One of the five compounds tested for effects on HMVEC migration, significantly inhibited migration on a fibronectin coated-surface by 78% (P&amp;lt;0.01). We have identified a number of small molecule inhibitors of TEM8, some of which display anti-angiogenic effects in vitro. Should these inhibitors also display potent anti-angiogenic effects in vivo, they may serve as lead compounds for the future development of TEM8 therapeutic small molecules. Future studies will focus on determining the effects of these molecules on tumor growth and angiogenesis in mouse models. Citation Format: Lorna Cryan, Marinya Roznik, Aaron McBride, Robert D'Amato, Kenneth Christensen, Michael S. Rogers. Identification and anti-angiogenic effects of small molecule inhibitors of TEM8. [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 5076. doi:10.1158/1538-7445.AM2013-5076
Fcγ receptor IIB gene polymorphism in adult Japanese patients with primary immune thrombocytopenia
Authors: Takashi Satoh, Koji Miyazaki, Asako Shimohira, Naoki Amano, Yuka Okazaki, Tetsuya Nishimoto, Tohru Akahoshi, Shinichi Munekata, Yuhsaku Kanoh, Yasuo Ikeda, Masaaki Higashihara, Shinichiro Takahashi, Masataka Kuwana
Journal: Blood (2013)
Abstract LB-425: Design of ß-cyclodextrin-curcumin self-assembly: A new approach for enhanced curcumin delivery and therapeutic efficacy in prostate cancer cells
Authors: Murali M. Yallapu, Meena Jaggi, Subhash C. Chauhan
Journal: Cancer Research (2010)

Abstract Curcumin (CUR), a hydrophobic polyphenolic compound derived from the rhizome of the herb Curcuma longa, has shown a wide range of biological applications including cancer prevention and treatment. However, low water solubility, poor pharmacokinetics and suboptimal tumor uptake, greatly hamper its anti-cancer efficacy. This study was designed to develop a novel ß-cyclodextrin-curcumin (CD-CUR) self-assembly approach for sustained release and improved curcumin delivery in prostate cancer cells. Cyclodextrin-curcumin self-assemblies were prepared by solvent evaporation technique. The formation of self-assemblies was evaluated by Fourier Transform Infra-red (FTIR), Differential Scanning Calorimetry (DSC), Thermo-gravimetric Analysis (TGA), Scanning and Transmission Electron Microscopic (SEM/TEM) analyses. Intracellular uptake of these self-assemblies was evaluated by Flow cytometry and immunofluorescence microscopy analyses. Therapeutic efficacy of these self-assemblies was determined by cell proliferation and colony formation assays using C4-2, DU145, LNCaP and PC3 prostate cancer cells. The effect of CD-CUR formulation on apoptosis related proteins was determined by immunoblotting. Physico-chemical characterization analyses confirm the formation of CD-CUR self-assemblies, which demonstrated excellent stability and solubility in physiological solutions and showed enhanced intracellular uptake in cells. Additionally, CD-CUR formulation has exhibited an improved therapeutic efficacy and enhanced PARP cleavage in prostate cancer cells compared to free curcumin. In conclusion, CD-CUR self-assemblies enhance intracellular delivery of active curcumin in prostate cancer cells and improved its therapeutic efficacy. This study suggests that CD-CUR self-assembly may be a useful nanoscale formulation for improved curcumin delivery in prostate cancer cells. Tumor specific antibody targeted CD-CUR formulation can further improve the in vivo delivery of curcumin in prostate tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-425.
P630Calmodulin/CaMKII inhibition accelerates conduction velocity by augmenting the localization of Cx43 in the intercalated disk
Authors: A Van Veen, H Takanari, V Bourgonje, MSC Fontes, HAJ Raaijmakers, H Driessen, MAG Van Der Heyden, HVM Van Rijen, I Kodama, MAG Vos
Journal: Cardiovascular Research (2014)

Purpose: In healthy hearts, ventricular gap junctions are composed by Connexin43 proteins (Cx43) and are localized in the intercalated disk (ID) where they enable appropriate electrical and metabolic coupling. During pathophysiological conditions, Cx43 is heterogeneously downregulated whereas the activity of CaM/CaMKII signaling increases. It is unclear if CaM/CaMKII affects the expression or the trafficking of Cx43. We analyzed several different models to assess the influence of CaM/CaMKII inhibition on Cx43 gap junctions and conduction properties of the heart. Methods: AC3-I mice, in which CaMKII was genetically inhibited, were subjected to pressure overload (16 wks, TAC vs sham) to evaluate the effect of chronic inhibition of CaMKII under pathological conditions. Conduction velocity (CV) was measured by high-resolution optical mapping and epicardial mapping on Langendorff perfused rabbit and AC3I mouse hearts respectively. Intercellular communication between cultured neonatal rat cardiomyocytes (CMs) was assessed by a dye transfer assay. Subcellular expression of junctional Cx43 from rabbit ventricles and cultured dog cardiomyocytes was evaluated by Triton X-100-based fractionation and Western blot (WB). Subcellular distribution of Cx43 in perfused rabbit and mouse ventricles was evaluated by immunohistochemistry. Results: In mice, CV was augmented in AC3-I sham (n=11, p<0.05 vs. WT) and preserved after TAC in the AC3-I mice (n=11), but impaired in TAC-WT mice (-20%). The expression of Cx43 was preserved after TAC surgery in AC3-I mice though arrhythmias were still present as was increased fibrosis. W7 (CaM inhibitor, 10 μM) significantly increased CV (+8%, n=4, p<0.05 vs. control) in rabbits while susceptibility to arrhythmias decreased. Immuno-confocal microscopy revealed enlarged Cx43 cluster sizes in the ID of W7 treated rabbit hearts. Total amount of Cx43 did not change by W7 (n=5), whereas junctional Cx43 increased (+10%, n=5, p<0.05). These data were confirmed in cultured dog cardiomyocytes both via treatment with W7 and KN93, (CaMKII inhibitor, 1-10 μM). Dye coupling in rat CMs improved (+37.5%, n=7, p<0.05 vs. control). Conclusion: Both acute and chronic CaM/CaMKII inhibition positively affects conduction properties and localization of Cx43 in ID. Only in absence of pathological fibrosis this reduced the susceptibility for arrhythmias.
P156 Can Specialist Nurses Predict Which Patients Will Readmit Following Delivery Of A Copd Care Bundle?
Authors: L. Sewell, C. Mitchell-Issitt, K. Barley, C. Chebbout, S. Msimanga, L. Clinch, S. Boyce, M. Steiner, S. Singh
Journal: Thorax (2014)

<h3>Introduction</h3> Adequate follow up is a key element of COPD care bundles (CB). COPD nurse specialists responsible for completing follow up consultations may be able to utilise clinical judgment and measures of health status to predict which patients are at greater risk of readmission. <h3>Objective</h3> We explored whether COPD nurse specialists working in the REspiratory Discharge Service (REDS), who delivered the CB, could predict whether patients would readmit within15 days post discharge. We also explored levels of health and psychological status for those patients who the REDS team thought were and were not at risk of readmission. <h3>Methods</h3> This was a retrospective audit of patients who received a COPD discharge CB from April 2013 to March 2014. Readmission likelihood was recorded by the REDS team after completion of a 2 day post-discharge phone consultation. Patients also completed the COPD Assessment Test (CAT), MRC breathlessness scale and the Hospital Anxiety and Depression Scale (HADS). Mean between-group differences for the ‘will admit’ and ‘will not admit’ groups were analysed using independent t-tests. <h3>Results</h3> Readmission risk was recorded for 1003 patients who received the CB prior to discharge. A total of 100 patients of these 1003 readmitted (readmission rate of 9.7%). The REDS team correctly predicted that 39 of these 100 patients would be readmitted. There were statistically significant between-group differences for MRC, CAT and HADS scores (see table): Patients placed in the ‘will readmit’ group had significantly worse CAT, HADS anxiety and depression scores compared those placed in the will not readmit group. <h3>Conclusions</h3> COPD nurse specialists were unable to correctly predict the majority of readmissions. Patients deemed at risk of readmision had worse levels of psychological and health status than those who were not thought to be at risk of readmission. This suggests other factors must be important in predicting COPD readmissions.
Abstract 60: The MedBook network for cancer precision medical care.
Authors: Theodore C. Goldstein, Robert Baertsch, Phillip G. Febbo, Josh Stuart, David Haussler
Journal: Cancer Research (2013)

Abstract Precision cancer care will connect clinical information to genomic information. To facilitate this connection, we are creating MedBook, a social networking system that links patients, physicians, and researchers in the battle against cancer. The Stand Up To Cancer West Coast Dream Team is first creating a bioinformatic platform that will run statistical and machine learning data analysis in a cloud-computing environment applied first to castration resistant prostate cancer and then share the data analysis results with oncologists and their patients. Patients, physicians, and researchers can also share sample data, high-throughput genomic discoveries, and their personal experiences in a safe structured environment covering research, disease course, and treatment. All data will be extracted from HIPAA repositories and anonymized and retain institutional review board controls. The social media model allows both the capture of unstructured information as well as collaborative discussions, annotation, and editing of structured information, to learn from each patient. Eventually, MedBook will collect knowledge about the experience of the disease from individual patients, from their treatments, and from their outcomes, and store them alongside relevant genomic molecular data. Our approach allows a variety of high-throughput genomic information to be generated and shared in a wiki-style collaborative network. This presentation will summarize the current state of MedBook and its utilization by a team of doctors and researchers across five medical centers and many university laboratories. Citation Format: Theodore C. Goldstein, Robert Baertsch, Phillip G. Febbo, Josh Stuart, David Haussler. The MedBook network for cancer precision medical care. [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 60. doi:10.1158/1538-7445.AM2013-60 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
REDUCTION IN ISCHEMIC EVENTS WITH TICAGRELOR IN DIABETIC PATIENTS FROM THE PEGASUS-TIMI 54 TRIAL
Authors: Deepak L. Bhatt, Marc Bonaca, Sameer Bansilal, Marc Cohen, Robert F. Storey, Kyungah Im, Sabina Murphy, Peter Held, Eugene Braunwald, Marc Sabatine, Ph Gabriel Steg
Journal: Journal of the American College of Cardiology (2016)
P210 Airways Resistance In Bronchial Challenge Testing
Authors: M. Baxter, D. Coates, A. Wilson
Journal: Thorax (2014)

<h3>Introduction</h3> Measurement of airways resistance is an alternative to spirometry to assess airflow obstruction. This can be measured by the interrupter technique (RInt) using a hand held device. We wished to know how RInt compared to forced expiratory volume in 1 second (FEV1) during a histamine challenge test. <h3>Methods</h3> Twenty-nine (13 male) patients, aged 48.9 (SD 15.3) years, referred for a histamine challenge test were enrolled. Patients had measurement of RInt then FEV1 after administration of saline and following doubling concentrations of histamine from 0.06 mg/ml to 8 mg/ml. Extrapolation of the log dose-response curve was undertaken to calculate the concentration (Provocation Concentration – PC) causing an increase airways resistance of 20, 40, 60, 80, 100, 120, 140 and 160% (RInt PC1.2 to RInt PC2.6) and a reduction in FEV1 by 20% (FEV1 PC20). The number of patients with a negative challenge (i.e. PC &gt; 8 mg/ml histamine) was calculated for FEV1 and each change in airway resistance. Patients assessed their procedure provoked symptoms of breathlessness, dizziness and tiredness on a 100 mm visual analogue scale. <h3>Results</h3> Geometric (SD) PC20 for FEV1 was 1.87 (0.5) mg/ml with 11 patients having a negative challenge. A RInt PC2.0 had the best agreement with FEV1 PC20 (Kappa 0.39 (p = 0.024)). There is a significant negative correlation between RInt and FEV1 (r = -0.94). The respective mean (SD) breathlessness, dizziness and tiredness scores for RInt were 26(4) mm, 18(3) mm, 22(4) mm and for spirometry were 40(4) mm, 27(5) mm, 31(5)mm. There was a significant (p &lt; 0.05) difference for breathlessness. <h3>Conclusion</h3> RInt was tolerated better than spirometry. A doubling of airways resistance had the best agreement with PC20 FEV1.
AB0231 Esophageal involvement in very early systemic sclerosis (SSC)
Authors: G. Lepri, S. Bellando Randone, G. Serena, I. Giani, G. Carnesecchi, C. Bruni, J. Blagojevic, A. Radicati, F. Pucciani, M. Matucci Cerinic
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> SSc affects gastrointestinal tract in more than 80% of patients. Esophageal involvement is the most common manifestation with a prevalence ranging between 50 and 90%. <h3>Objectives</h3> Evaluation of esophageal involvement and detection of its predictor factors in very early SSc patients. <h3>Methods</h3> 56 patients (55 females), mean age 49,2±14 years, with very early SSc were evaluated with esophageal manometry. The demographic data, esophageal symptoms (dysphagia, typical GERD symptoms), Raynaud phenomenon (presence/absence, duration), autoantibody profile (anticentromere antibodies [ACA], antinuclear antibodies [ANA], anti-Scl70 antibodies [Scl70]), videocapillaroscopy patterns (Normal, Early, Active, Late), puffy fingers, digital ulcers were recorded for all patients. <h3>Results</h3> Esophageal body dysmotility (abnormal mean pressure of peristalsis or absence of peristalsis) was present in 49 patients (94,2%), and was associated with a hypotensive lower esophageal sphincter (LES) in 26 (53,1%). Esophageal symptoms were present in 26 patients (50%).Puffy fingers were present in 22 patients (42,3%) and were associated with a smaller area of LES (<i>p-value: 0.011)</i>. In 4 patients esophageal manometry was not performed because of scarce tolerance of the procedure. <h3>Conclusions</h3> Esophageal disorders are frequently seen in very early SSc patients in particular in patients with puffy fingers. <h3>Disclosure of Interest</h3> None Declared
OUTCOMES OF SUBCUTANEOUS IMPLANTABLE CARDIOVERTER DEFIBRILLATOR IMPLANT IN RENAL DIALYSIS PATIENTS
Authors: Mathew Levy, Faisal Merchant, Mary Casey, Michael Hoskins, Michael Lloyd, Angel Leon, David DeLurgio, Abhinav Goyal, Mikhael El-Chami
Journal: Journal of the American College of Cardiology (2015)
PERCENT REDUCTION OR TARGET-BASED STRATEGIES TO MANAGE BLOOD CHOLESTEROL IN SUBJECTS AT INTERMEDIATE RISK: CARDIOVASCULAR BENEFIT VERSUS DIABETES ONSET RISK IN REAL WORLD PATIENTS
Authors: Fernando H.Y. Cesena, Antonio Laurinavicius, Marcio Bittencourt, Raquel Conceicao, Raul Santos
Journal: Journal of the American College of Cardiology (2016)
Abstract 2707: Long-term significance (15 years) of pathological complete response after dose-dense neo-adjuvant chemotherapy in breast cancer
Authors: Qian Wang-Lopez, Catherine Abrial, Eloise Planchat, Marie-Ange Mouret-Reynier, Hervé Cure, Pierre Gimbergues, Pascale Dubray-Longeras, Dominique J. Gallon-Bernard, Fabrice Kwiatkowski, Philippe J. Chollet, Xavier Durando
Journal: Cancer Research (2012)

Abstract Purpose: As a contribution to the discussion of pathological complete response (pCR) as surrogate end-point, after neo-adjuvant chemotherapy (NACT), we studied disease-free survival (DFS) and overall survival (OS) at 15 years with THP-doxorubicin, vinorelbine, 5-Fluorouracil and cyclophosphamide (TNCF regimen). Patients and methods: This retrospective cohort study has been done in 61 patients treated with neo-adjuvant semi-intensive chemotherapy. PCR rate was analysed separately in breast (no histological evidence of invasive tumor cells and / or presence of in situ carcinoma tumor cells) and in nodes (no metastasis). Univariate and multivariate analysis (COX regression) have been used to assess the potential prognostic factors with a median follow up of 13.8 years. Results: Thirty two patients relapsed and 21 died. At 15 years, DFS and OS were 53% and 88% respectively for the patients who achieved pCR compared to 33% and 53% respectively for those who did not achieve pCR. Multivariate analysis with COX model showed that pCR in breast and the number of involved nodes at surgery were 2 factors who can significant predict patients’ DFS and these two factors were significantly related. Conclusion: In this current study, pCR in breast can be used as surrogate marker to predict survival outcome, even with a long-term follow-up of 15 years. When pathological response was incomplete in primary tumor, the number of involved nodes (n &amp;gt; 4 vs n &amp;lt;/= 4) significantly predicted survival. 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 2707. doi:1538-7445.AM2012-2707