tbuckley/cabot-search huggingface dataset:
Abstract 825: The development of a novel PARP inhibitor with potent antitumor activity in various tumor xenograft models
Authors: Ji-Seon Park, Jang-Hyun Kim, Kwang-Woo Cheon, Bo-Young Cho, Kang-Jeon Kim, Han-Chang Lee, Young-Cheol Kim, Hyung-Chan Oh, Hyun-Ho Lee, Jeong-Min Kim
Journal: Cancer Research (2014)

Abstract Poly (ADP-ribose) Polymerase (PARP) plays a critical role in DNA repair processes. Small molecule inhibitors of PARP for the treatment of cancer are currently being investigated either single agents or in combination therapy with other DNA damaging agents. Based on recent published data, PARP inhibitors have shown promising results as a powerful therapeutic anticancer agents, especially in tumors deficient in BRCA-1or BRCA-2 function. In this study, we present a novel synthetic inhibitor of poly (ADP-ribose) polymerase (PARP) for their anti-tumor activity in various types of tumor xenograft model. Among new synthetic PARP inhibitors, JPI-283 shows synergistic effects in vitro cell cytotoxicity with DNA damaging agent such as Temozolomide(TMZ), SN-38, and CDDP. Also, JPI-283 represents a potential anticancer activity in BRCA-1 and BRCA-2 mutant cells as a single agent. In tumor xenograft model studies, the combination of JPI-283 with TMZ by oral dosing results in more than 60-70% tumor growth inhibition rate, compared to the control group in CAPAN-1, U87MG, MDA-MB-468 and SW620 tumor xenograft model. In addition, the combination of JPI-283 with CDDP shows superior antitumor activity compared to that of AZD2281 with CDDP in MDA-MB468 triple negative breast tumor xenograft model. The pharmacokinetics of JPI-283 in mouse and rat shows over 50% bioavailability. These findings suggest that JPI-283 would be an attractive therapeutic candidate for the treatment of cancer including DNA repair deficient cancer. Citation Format: Ji-Seon Park, Jang-Hyun Kim, Kwang-Woo Cheon, Bo-Young Cho, Kang-Jeon Kim, Han-Chang Lee, Young-Cheol Kim, Hyung-Chan Oh, Hyun-Ho Lee, Jeong-Min Kim. The development of a novel PARP inhibitor with potent antitumor activity in various tumor xenograft models. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 825. doi:10.1158/1538-7445.AM2014-825
Abstract 4271: The cBioPortal for Cancer Genomics as a clinical decision support tool
Authors: JianJiong Gao, B. Arman Aksoy, Benjamin Gross, Gideon Dresdner, Yichao Sun, S. Onur Sumer, Chris Sander, Nikolaus Schultz
Journal: Cancer Research (2014)

Abstract As sequencing of tumor samples is entering clinical practice, there is an urgent need for new tools that facilitate the interpretation of sequence data so that they can effectively inform treatment decisions. To this end, we are evolving the cBioPortal for Cancer Genomics into a clinical decision support tool. The cBioPortal is a web-based visualization and analysis engine that makes complex cancer genomics data accessible to a wide range of cancer researchers and clinicians. To transition the cBioPortal towards use in clinical practice, we have recently developed the following new functions: 1. Filtering of oncogenic mutations: By using information about the known or likely oncogenic effects of specific mutations, the portal can now filter out passenger events and highlight known and potentially druggable drivers. 2. Clinical timelines: Compact and interactive visualization of a patient's clinical and treatment history 3. Image support: Interactive visualization of histology images 4. Support for multiple tumor samples from a single patient: The portal can display genomic differences and similarities of different samples (e.g. multiple sites of the same tumor, recurrence, metastasis, post-treatment) in the context of a patient's treatment history. 5. Tumor clonality: Assessment of a tumor's purity and clonality / heterogeneity 6. Targeted treatment suggestions: The portal matches drugs to drug targets that are altered in the patient's tumor. 7. Clinical trial matching: Based on a patient's clinical history and the genomic alterations found in the tumor, the cBioPortal will identify relevant clinical trials. By making complex genomic data easily interpretable and linking it to information about drugs and clinical trials, the system has the potential to facilitate the proper use of genomic data in clinical decision making. We are constantly improving the software and will initially focus most strongly on the matching of patients to clinical trials. We are sharing the software with other hospitals, where it can be used by oncologists and tumor boards. Citation Format: JianJiong Gao, B. Arman Aksoy, Benjamin Gross, Gideon Dresdner, Yichao Sun, S. Onur Sumer, Chris Sander, Nikolaus Schultz. The cBioPortal for Cancer Genomics as a clinical decision support tool. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4271. doi:10.1158/1538-7445.AM2014-4271
Abstract 3653: Aortic Compliance and Angina in Women without Coronary Artery Calcification: An Analysis from the Dallas Heart Study
Authors: Kamakki Hayes, Divijani Puttagunta, James de Lemos, Mahesh Patel, Alice Chang, Ronald Peshock, Darren K McGuire, Amit Khera
Journal: Circulation (2007)

Background:  Angina in women without CAD (syndrome X) is a morbid illness that may be related to microvascular dysfunction. We sought to determine if there is an association between this entity and large artery dysfunction.   Methods:  The Dallas Heart Study is a population-based study of subjects ages 30 – 65. MRI images through the ascending aorta were used to determine aortic compliance (AC), which was calculated as the change in aortic volume/ brachial artery pulse pressure. Angina was defined using the Rose Angina questionnaire and coronary artery calcium (CAC) was assessed using CT. The study was restricted to women with no CAC (scores ≤10 Agatston units) who had complete Rose Angina and AC data.   Results:  Of the 1126 women in this study (mean age 44 ± 9 years, 48% black) 7% (n=83) had angina. Women with angina versus those without had lower AC (22.5 ± 10.6 v. 26.4 ± 12.1 mL/mmHg, p   Conclusions : AC is inversely associated with angina in women without CAC. Further studies are needed to determine whether reduced AC contributes to angina directly, or if both reduced AC and syndrome X are the result of similar pathophysiology.
Abstract #5502: Inhibition of Notch signaling for the treatment of human carcinomas
Authors: Agamemnon Epenetos, Christina Kousparou, Spyros Stylianou
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Inhibition of Notch signaling for the treatment of human carcinomas Agamemnon Epenetos, Christina Kousparou, Spyros Stylianou Trojantec Ltd, the Bank of Cyprus Oncology Centre Nicosia, Cyprus Notch signaling is an evolutionary-conserved pathway in vertebrates and invertebrates which is involved many developmental processes, including cell fate decisions, apoptosis, proliferation, and stem-cell self renewal. There is increasing evidence that the same molecular pathways regulating the self renewal of stem cells are also being employed in cancer progression. The Notch signal transduction pathway has been implicated in the self-renewal of stem cells in hematopoietic, skin, neural, germ and breast tissue. Increasing evidence suggests that the Notch signaling pathway is frequently up regulated in many forms human malignancies including acute T-cell lymphoblastic leukemia, cervical, prostate, lung, breast and inhibition of the pathway could be a novel therapeutic approach for the treatment of human carcinomas. Furthermore, aberrant Notch regulation during the self-renewal of stem cells may cause certain human cancers. Thus, this pathway offers an attractive potential to target the cancer stem cells resulting in innovating cancer treatments. We have genetically engineered a fusion protein, consisting of the Drosophila transcription factor Antennapedia (ANTP) and with the truncated version of Mastermind-like (MAML) that behaves in a dominant negative (DN) fashion and inhibits Notch activation (ANTP/DN MAML, TR4). This novel fusion protein has been tested for its ability to target tumor cells in vitro and in vivo. Our data show that ANTP/DN MAML fusion protein, TR4 contains signals for proper cell targeting, internalization and nuclear transport. Furthermore, TR4 inhibits human mammary and colon xenograft tumor growth and metastases in immuno deficient mice. The immunogenicity and toxicity of TR4 was investigated in normal immuno-competent mice and the results indicate no immune responses or toxicity. Of interest, TR4 presence and activity was also detected in the brains of treated animals demonstrating that TR4 can cross the blood-brain barrier and potentially eliminate brain tumors and metastases, unlike other anticancer drugs and biologicals such as monoclonal antibodies that cannot cross the blood brain barrier.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5502.
The effects of consumerism
Authors: Jason O'Neale Roach
Journal: BMJ (2001)

The rise of consumerism means that the public now demands health services, rather than accepts what is on offer. The health service will need to become almost unrecognisable in its role and function to survive. A book entitled Developing New Clinical Roles examines the need for a fresh approach, in a health system with constantly increasing demands. Flexible training—the subject of a paper in …
‘Addressing’ an under-recognized cause of discomfort for patients undergoing Mohs micrographic surgery
Authors: J. Parker, D. Norman, L. Savage, W. Hussain
Journal: British Journal of Dermatology (2013)

Journal Article ‘Addressing’ an under‐recognized cause of discomfort for patients undergoing Mohs micrographic surgery Get access J. Parker, J. Parker Department of Mohs Surgery (C4), Leeds Centre for Dermatology, Chapel Allerton Hospital, Leeds LS7 4SA, U.K Search for other works by this author on: Oxford Academic Google Scholar D. Norman, D. Norman Department of Mohs Surgery (C4), Leeds Centre for Dermatology, Chapel Allerton Hospital, Leeds LS7 4SA, U.K Search for other works by this author on: Oxford Academic Google Scholar L. Savage, L. Savage Department of Mohs Surgery (C4), Leeds Centre for Dermatology, Chapel Allerton Hospital, Leeds LS7 4SA, U.K Search for other works by this author on: Oxford Academic Google Scholar W. Hussain W. Hussain Department of Mohs Surgery (C4), Leeds Centre for Dermatology, Chapel Allerton Hospital, Leeds LS7 4SA, U.K Correspondence: Walayat Hussain. E‐mail: dr_w_hussain@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 169, Issue 1, 1 July 2013, Pages 187–188, https://doi.org/10.1111/bjd.12213 Published: 01 July 2013
ESSENTIAL THROMBOPHILIA: REPORT OF A CASE
Authors: J A EPSTEIN, I H RICHTER
Journal: Annals of Internal Medicine (1948)

Case Reports1 September 1948ESSENTIAL THROMBOPHILIA: REPORT OF A CASEJOSEPH A. EPSTEIN, M.D., ISAAC H. RICHTER, M.D.JOSEPH A. EPSTEIN, M.D.Search for more papers by this author, ISAAC H. RICHTER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-29-3-545 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn this communication we wish to present a case which clinically and pathologically conforms to the disease entity known as "Essential Thrombophilia." In 1937, Nygaard and Brown defined this syndrome and reported five cases in which thrombosis occurred in the vessels of the extremities and in the brain, kidney and heart. The thrombosis occurred without any previously known disease of the vessels involved such as is seen in thromboangiitis obliterans and in arteriosclerosis. The pathological changes in the vessels were minimal and of a non-reacting type. Thrombosis was evident without signs of disease in the intima and in the other...Bibliography1. NYGAARDBROWN KKGE: Essential thrombophilia. Report of five cases, Arch. Int. Med., 1937, lix, 82-106. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *Received for publication November 1, 1946.From the Department of Pathology and the Peripheral Vascular Clinic of the Jewish Hospital of Brooklyn.†Assistant Resident in Surgery. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThrombocytosis and ThrombocythemiaThrombozytose und Thrombozythämie-Symptom oder selbständiges Krankheitsbild?ESSENTIAL THROMBOCYTHEMIA*HENRY G. KUPFER, M.D., BRUCE J. EBBELS, M.D., JOHN N. MILLER, M.D., GEORGE W. THOMA, M.D., SIMON RUSSI, M.D.Acute arterial thromboses involving major vessels 1 September 1948Volume 29, Issue 3Page: 545-549KeywordsBrainHeartHospitalsKidneysSurgeryThrombosis ePublished: 1 December 2008 Issue Published: 1 September 1948 PDF downloadLoading ...
Abstract 4344: Biventricular Pacemaker Therapy Corrects Dyssynchrony in Non-Obstructive Hypertrophic Cardiomyopathy
Authors: Ibrar Ahmed, Khalid Abozguia, Ganesh Nallur-Shivu, Thanh T Phan, Abdul Maher, Berthold Stegemann, Rodolphe Katra, Kiran Patel, Francisco Leyva, John Sanderson, Denis Pellerin, Perry Elliott, Michael Frenneaux
Journal: Circulation (2008)

Background. Previous studies have reported dyssynchrony using Tissue Doppler in patients with hypertrophic cardiomyopathy (HCM). In this study we assessed dyssynchrony using speckle tracking echocardiography (STE) in patients with non-obstructive hypertrophic cardiomyopathy vs a healthy control group and in a subgroup of highly symptomatic patients evaluated the acute effects of biventricular pacing on STE and Tissue Doppler (TDI) derived measures of dyssynchrony. Methods. We studied 48 healthy controls (age 48 ±18yrs, 22 males, LVEF 63 ±5%, QRS 86 ±7ms) and 57 patients with HCM (age 54 ±11yrs, 38 males, LVEF 61 ±7%, QRS 110 ±36ms). A subgroup of 15 symptomatic patients with HCM (Peak VO2&lt;60% predicted) underwent biventricular pacing (age 53 ±12yrs, 12 males, LVEF 61 ±7%, QRS 110 ±32ms). Echocardiography was performed with the pacemaker off (VVi30) and on (DDDR, AV delay 90ms, LV-RV delay 0 – 4ms). Using STE, the standard deviation (SD) in time to peak longitudinal strain (Tϵ-SD), the time to peak longitudinal systolic velocity (Ts) for each of 18 left ventricular segments and the SD of this timing (Ts-SD) was derived. Using TDI dyssynchrony was assessed from the SD of Ts for the basal six segments and the maximum difference in Ts between any two basal segments (Ts-peak[basal]). Results. Using STE, Tϵ-SD (54.99 ±33.61ms vs 24.55 ±21.18ms p&lt;0.001), Ts-SD (71.06 ±32.32ms vs 46.17 ±21.50ms p&lt;0.001) and Ts (155.74 ±23.14ms vs 123.71 ±11.25ms p&lt;0.001) were greater in HCM than in controls. Using STE we demonstrated that biventricular pacing significantly reduced Tϵ-SD and Ts-SD to values similar to those observed in controls (Ts-SD p=0.13). Using TDI we demonstrated that biventricular pacing significantly reduced Ts, Ts-SD, and Ts-peak[basal]. See Table . (All values expressed as mean ±SD) Conclusion. Cardiac resynchronisation therapy significantly reduced dyssynchrony in symptomatic patients with non-obstructive HCM as demonstrated using STE and TDI. Table
Abstract 9476: Atrial Septostomy in Patients with Pulmonary Arterial Hypertension
Authors: Eric R Fenstad, Rachel J Le, Michael D McGoon, Guy Reeder, Donald J Hagler, Allison K Cabalka, Garvan C Kane, Robert P Frantz
Journal: Circulation (2011)

Introduction: Creation of an atrial septal defect via atrial septostomy (AS) is a therapeutic option traditionally utilized for PAH in settings where medical therapy was unavailable. Its utility in the context of progressive disease despite medical therapy remains incompletely understood. Hypothesis: AS may be a useful option in patients with symptomatic PAH despite medical therapy and may improve functional class. Methods: Single center retrospective study of all adult PAH patients receiving AS at a tertiary PAH referral center. Results: Eleven atrial septostomy procedures were performed in 8 patients who were refractory to maximal medical management. All patients were WHO functional class III or IV and average patient age was 40 ± 13 years with a female predominance (89%). Mean RA pressure was 18 ± 4 mm Hg with cardiac index of 2.28 ± 0.82 L/min/m 2 prior to AS. Mean pulmonary artery pressure was 63 mm Hg with a pulmonary artery saturation of 48% and average systolic blood pressure of 97 mm Hg. Baseline NT-proBNP was 5573 ± 4589 pg/ml with a mean 6 minute walk distance (6MWD) of 311 ± 131 meters. Five of the 11 procedures resulted in functional class improvement. Functional class change did not relate to change in 6MWD or NT-pro BNP level. Three patients had repeat AS due to spontaneous narrowing of the original septostomy, with a mean duration of 220 ± 135 days between procedures. One patient died within 30 days of the procedure and another at day 88 while one patient received a heart/lung transplant at day 42 post AS. Mean follow up was 243 ± 183 days. The REVEAL risk scores ranged from 10 to 15, with predicted 1 year survival from pre-septostomy clinical data ranging from 22% to 80% (mean predicted survival of 57%). Actual transplant free survival at 1 year was 63%. Conclusions: Selected patients at high risk for 1 year mortality may receive symptomatic benefit from atrial septostomy. One year mortality remains high, and not significantly different from that predicted by the REVEAL score. Atrial septostomy may be a palliative treatment option for patients who are refractory to maximal medical therapy but further long term investigation is necessary.
Mutations in the XPD helicase gene result in XP and TTD phenotypes, preventing interaction between XPD and the p44 subunit of TFIIH
Authors: Frédéric Coin, Jean-Christophe Marinoni, Carlo Rodolfo, Sébastien Fribourg, Antonia Maria Pedrini, Jean-Marc Egly
Journal: Nature Genetics (1998)
312. Developing Qualified Activity and Potency Assays for Gene Therapy and DNA Vaccine Products
Authors: Hiroyasu Kinoshita, Sanae Hisayasu, Atsushi Watanabe, Satoru Suzuki, Takashi Shimada
Journal: Molecular Therapy (2004)

Purpose: Development of targeted gene transfer technologies is essential for in vivo gene therapy. Adenoviral vectors are capable of gene transfer into a wide variety of cell types but often elicit severe immune-inflammatory responses. A serious adverse event due to systemic inflammatory response syndrome was recently reported after infusion of an adenoviral vector into the liver. To minimize toxicity to the liver, gene transfer and expression should be localized to limited liver segments. In the present study, we examined the feasibility of physical targeting to the selected liver segments using catheterization techniques. Methods: Procedure 1: A vascular clamp was placed across the portal vein (PV) between the upper and the lower segments of the liver in Wistar rats. An adenoviral vector carrying the LacZ gene, AxCALacZ, was infused through the proximal PV. The clamp was removed 5 min later. Procedure 2: Isolated hepatic perfusion technique was applied in addition to clamping as procedure 1. Both PV and the hepatic inferior vena cava (IVC) were cannulated, while the other vasculatures were all clamped. The adenovirus vector was injected through the PV catheter and unbound vector particles were washed out with PBS. The outflow solution from the circulation was collected to the IVC catheter. Results: The beta-gal activity was significantly higher in the proximal segments compared to the distal segments in both procedures. Moderate beta-gal activity was also detected in the spleen in procedure 1, while the activity was hardly detectable in procedure 2. The levels of inflammatory cytokines were reduced by isolated hepatic perfusion. Conclusion: Isolated hepatic perfusion with clamping of specific portal vein branches is useful for adenoviral-mediated local gene delivery to selected liver segments and could be applied to treatment of focal liver diseases such as liver metastases of cancer.
Sensitive <i>KIT</i> D816V mutation analysis of blood as a diagnostic test in mastocytosis
Authors: Thomas Kristensen, Hanne Vestergaard, Carsten Bindslev‐Jensen, Michael Boe Møller, Sigurd Broesby‐Olsen
Journal: American Journal of Hematology (2014)

The recent progress in sensitive KIT D816V mutation analysis suggests that mutation analysis of peripheral blood (PB) represents a promising diagnostic test in mastocytosis. However, there is a need for systematic assessment of the analytical sensitivity and specificity of the approach in order to establish its value in clinical use. We therefore evaluated sensitive KIT D816V mutation analysis of PB as a diagnostic test in an entire case-series of adults with mastocytosis. We demonstrate for the first time that by using a sufficiently sensitive KIT D816V mutation analysis, it is possible to detect the mutation in PB in nearly all adult mastocytosis patients. The mutation was detected in PB in 78 of 83 systemic mastocytosis (94%) and 3 of 4 cutaneous mastocytosis patients (75%). The test was 100% specific as determined by analysis of clinically relevant control patients who all tested negative. Mutation analysis of PB was significantly more sensitive than serum tryptase >20 ng/mL. Of 27 patients with low tryptase, 26 tested mutation positive (96%). The test is furthermore readily available and we consider the results to serve as a foundation of experimental evidence to support the inclusion of the test in diagnostic algorithms and clinical practice in mastocytosis.
Initial two years of experience with the AAO National Eyecare Outcomes Network (NEON) cataract surgery database11NEON is a program of the American Academy of Ophthalmology. Covance Health Economics and Outcomes Services Inc. is a consultant to, and provides technical support for, NEON under contract to the AAO.
Authors: Flora Lum, Oliver Schein, Andrew P Schachat, Richard L Abbott, H.Dunbar Hoskins, Earl P Steinberg
Journal: Ophthalmology (2000)
The Welfare State and the National Welfare: A Symposium on Some of the Threatening Tendencies of Our Times
Authors: Sheldon Glueck
Journal: JAMA (1952)

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