tbuckley/cabot-search huggingface dataset:
Pharmacodynamic analysis of receptor tyrosine kinase (RTK) activity reveals differential target inhibition in skin and tumor in a phase I study of advanced colorectal cancer patients treated with AEE788
Authors: D. W. Davis, J. Huang, W. Liu, L. Xiao, A. Thomas, A. Mita, W. Steward, C. Takimoto, W. Mietlowski, H. Xiong
Journal: Journal of Clinical Oncology (2007)

3601 Background: AEE788 (AEE) is an oral inhibitor against tyrosine kinases and has an IC 50 of &lt; 100 nM against EGFR and VEGFR-2. This PD study investigated the effects of AEE on its targets in vitro and in biopsies from advanced colorectal cancer patients. Methods: HUVECs and HT-29 cells were incubated with AEE for 4h at 0–1 mM. 22 pts were treated at doses of 25 (n=4), 50 (n=3), 100 (n=4), 250 (n=1), 300 (n=4), and 400 mg (n=6) mg/day in 28-day cycles. No major clinical respones were observed. Wound-induced paired skin biopsies were performed on days -8, -1, 22, 29. Tumor biopsies were obtained before and 28 days post-treatment. Evaluable paired skin and tumor samples were available in 18 and 14 patients respectively. The effects of AEE on pKDR, pEGFR, AKT, Ki67, and apoptosis were analyzed by laser scanning cytometry (LSC). Wilcoxon signed rank test and Spearman correlation were used to compare biomarker changes post-treatment and correlation with dose, respectively. Results: In vitro, AEE treatment resulted in a dose-dependent inhibition of pKDR and pEGFR with inhibition of 65% and 63% at 1 mM in HUVECs and HT-29 cells, respectively. pKDR levels increased in response to AEE treatment in HT-29 cells. In skin, AEE increased basal levels of pKDR (p=0.03) post-treatment. AEE increased AKT (p=0.02) and EGFR (p=0.01) in a dose-dependent manner. In wound-induced skin pairs, AEE significantly inhibited endothelial cell pKDR/KDR (ratio) in a dose-dependent manner (p=0.02). In tumors, AEE increased pKDR expression (p=0.05) and was dose-dependent (p=0.06). Tumor endothelial cell pKDR levels decreased (avg. 47%) after AEE treatment (p=0.08). Furthermore, levels of Ki67 increased (p=0.08) and no significant effects were observed on pEGFR or apoptosis at any dose level in post-treatment samples. Conclusions: LSC quantitative analysis confirmed the target inhibition of AEE in vitro and in wound-induced skin pairs. The lack of significant target inhibition in tumors is consistent with the lack of clinical activity of AEE in this cohort of patients. Quantifying pKDR/KDR in wound-induced skin pairs may serve as a surrogate for assessing the activity of an angiogenesis inhibitor such as AEE. [Table: see text]
TRENDS AND OUTCOMES OF AORTIC VALVE REPLACEMENT IN PATIENT WITH END STAGE RENAL DISEASE ON HEMODIALYSIS: A 10-YEAR U.S. PERSPECTIVE
Authors: Fahad Alqahtani, Sami Aljohani, Ahmed Almustafa, Ashwin Bhirud, Khaled Boobes, Chalak Berzingi, Sameer Raina, Wissam Gharib, Mohamad Alkhouli
Journal: Journal of the American College of Cardiology (2017)
3-MONTH AND 6-MONTH PRIMARY PATENCY WITH STENT VERSUS BALLOON ANGIOPLASTY FOR FAILING ARTERIOVENOUS GRAFTS FAILURE: A META-ANALYSIS
Authors: Konstantinos Marmagkiolis, Cezar Iliescu, Konstantinos Charitakis, Mehmet Cilingiroglu
Journal: Journal of the American College of Cardiology (2017)
ASSOCIATION OF ABDOMINAL AORTIC WALL INFLAMMATION, HEPATIC FLUORODEOXYGLUCOSE UPTAKE AND VISCERAL ADIPOSE TISSUE BIOLOGICAL ACTIVITY IN PATIENTS WITH DYSLIPIDEMIAS
Authors: Koutagiar Peter Iosif, Konstantinos Toutouzas, Georgios Benetos, Nikoletta Piannou, Alexios Antonopoulos, Alexandros Georgakopoulos, Ioannis Skoumas, Spyridon Galanakos, Angeliki Rigatou, Pavlos Kafouris, Andreas Synetos, George Spyrou, Charalambos Antoniades, Eleftherios Tsiamis, Constantinos Anagnostopoulos, Dimitris Tousoulis, First Department of Cardiology, Medical School
Journal: Journal of the American College of Cardiology (2017)
NON-TRANS FEMORAL TRANS CATHETER AORTIC VALVE REPLACEMENT IN NONAGENARIANS WITH SEVERE AORTIC STENOSIS: A MATCHED CASE-CONTROL PILOT STUDY
Authors: Alexis Okoh, Dhaval Chauhan, Nathan Kang, Nicky Haik, Bruce J. Haik, Chunguang Chen, Mark Russo
Journal: Journal of the American College of Cardiology (2017)
INCIDENCE AND PREDICTORS OF NO REFLOW PHENOMENON: INSIGHTS FROM THE TOTAL TRIAL
Authors: Ashraf M. Al Azzoni, Pablo Lamelas, Tamara Marsden, Vladimir Dzavik, John Cairns, Brandi Meeks, Shamir Mehta, Madhu Natarajan, Tej Sheth, Jon-David Schwalm, Sunil Rao, Goran Stankovic, Sasko Kedev, Sanjit Jolly
Journal: Journal of the American College of Cardiology (2017)
FXIIa Differentially Regulates Thrombin Generation during Steady State and Vaso-Occlusive Crisis in Sickle Cell Mice
Authors: Erica M Sparkenbaugh, Camille Faes, Denis Noubouossie, Daniel K. Kirchhofer, András Gruber, Nigel S. Key, Rafal Pawlinski
Journal: Blood (2016)
Evaluation of Potential role for Valproic Acid in IL-3-Mediated Megakaryopoiesis and Erythropoiesis in Serum-Free and Serum-Containing Cultures.
Authors: Kohshi Ohishi, Bing Liu, Masahiro Masuya, Yuji Heike, Yoichi Takaue, Naoyuki Katayama
Journal: Blood (2009)
NATIONAL TREND IN TOTAL CHARGES FOR MULTIVESSEL PERCUTANEOUS CORONARY INTERVENTION IN PATIENTS WITH DIABETES MELLITUS IN THE UNITED STATES: NATIONWIDE INPATIENT SAMPLE FROM THE YEAR 2006 TO 2011
Authors: Apurva Patel, Hemang Panchal, Shimin Zheng, Ashraf Abusara, Eunice Mogusu, Timir Paul
Journal: Journal of the American College of Cardiology (2017)
CD14+ hla-DR-/Lo Myeloid-Derived Suppressor Cells Express Immunosuppressive B7-H Family Members and Are Depleted Following Taxane-Based Chemotherapy in Melanoma.
Authors: Ryan A Wilcox, Wendy K Nevala, Michael A Thompson, Thomas E Witzig, Stephen M Ansell, Svetomir N Markovic
Journal: Blood (2009)
The PI3K/mTOR inhibitor BEZ235 given twice daily for the treatment of patients (pts) with advanced solid tumors.
Authors: Hendrik-Tobias Arkenau, Suzanne Fields Jones, Carla Kurkjian, Jeffrey R. Infante, Shubham Pant, Howard A. Burris, Kathleen N. Moore, D. Scott McMeekin, Frank A. Greco, Sara Ramsey, Johanna C. Bendell
Journal: Journal of Clinical Oncology (2012)

3097 Background: The PI3 kinase (PI3K) pathway is the most deregulated pathway in cancers and is an attractive target for antitumor therapy. BEZ235 is an oral highly specific and selective inhibitor of the PI3K and TORC1/2. The MTD (1200 mg) and toxicity profile of BEZ235 once daily dosing has been established. This study was designed to evaluate twice daily dosing of BEZ235 and its effect on treatment tolerability, PK, PD, and preliminary efficacy. Methods: Pts with advanced disease were enrolled in a 3+3 dose escalation schedule starting at 200 mg PO BID in 28 day cycles. For intrapatient PK comparison the first week pts received the total dose in a QD schedule. DLT assessment was in Cycle 1. Efficacy evaluations were every 2 cycles, and PK and PD were assessed. Results: 12 pts were enrolled at the following dose levels: 200 mg (n=3), 400 mg (n=3), 600 mg (n=3), and 600 mg (BID only, no QD lead-in) (n=3). No G4 AEs were reported. G3 related AEs were mucositis (n=2), AST/ALT elevation (n=2), anorexia (n=1) and diarrhea (n=1). The most common related G1/2 adverse events (AEs) were anorexia (n=6), diarrhea (n=3), fatigue (n=2), and headache (n=2). DLTs of G3 mucositis were observed in 2 patients at the 600 mg BID dose level with 1 week 1200 mg QD lead-in, which were attributed to the QD lead-in dosing during the first week. 3 pts then enrolled at 600 mg BID without lead in and had no further DLT. PK shows consistent increase in PK parameters with dose level. Of 10 evaluable, 3 pts had stable disease (13+ to 21+ weeks, 2 colorectal, 1 endometrial). Of 9 evaluable, 4 pts at various dose levels had decreased PET SUV uptake by greater than 25%. Conclusions: BEZ235 is tolerable at a dose of 600 mg BID, with less toxicity than has been seen with equivalent QD dosing. Preliminary signs of clinical and PD activity are noted.
Romiplostim in Patients Undergoing Allogeneic Stem Cell Transplantation: Results of a Phase I/II Multicenter Trial
Authors: Régis Peffault de Latour, Sylvie Chevret, Annalisa Ruggeri, Felipe Suarez, Laetitia Souchet, David Michonneau, Flore Sicre de Fontbrune, Tereza Coman, Marie t Rubio, Stéphanie Nguyen, Mohamad Mohty, Gerard Socie
Journal: Blood (2016)
Prognostic value of Bcl-2 in breast cancer.
Authors: Patricia Ibeas, Ana Lopez-Gonzalez, Bernard Gaston Doger de Speville, Miriam Huelves, Roberto Lopez, Elena Almagro, Magda Palka, Andrea Ruiz-Valdepeñas, David Perez Callejo, Mariano Provencio
Journal: Journal of Clinical Oncology (2012)

e11527 Background: Breast cancer is a heterogeneous disease with prognostic factors used by the oncologists to decide the treatment. Bcl2 is an antiapoptotic proto-oncogen involved in DNA break process that has been defined historically as a poor prognostic factor. This study was conducted to confirm whether or not bcl-2 is an independent prognostic factor. Methods: In this study, we have reviewed all patients who were diagnosed at our hospital between January 2007 and December 2008 (99 patients). Inclusion criteria were patients diagnosed of breast cancer whose anatomopathological report showed bcl-2 status as well as the rest of the parameters measured. The parameters measured were age, past medical history, menopausal status, TNM, hormone receptors, HER2, p53, Ki67, bcl-2, treatment applied, date of relapse (if any), date of death ( if occurred). All of them characterized by centralization measures. We conducted an analysis of prognostic factor that influenced survival. Results: The average age of diagnosis is 54.6 years (30-94 years). 42.4% were premenopausal. The average tumor size was 2.59 cm ( 0.5-7.5 cm). 81.8% had positive estrogen receptors. 92% were HER2 negative by inmunohistochemistry. 62.6% were p53 negative. Bcl-2 was 84.8% positive. The distribution by stage at diagnosis was: stage I 26.3%; stage II 49.5%; stage III 22.2%. Disease free survival for patients bcl2(+) was 45.6 months versus 22.6 months for patients bcl2 (-) (0.12-22.2; p: 0.00125). Overall survival for the group bcl2(+) was 48 months (41.6-54.3) and bcl2 (-) was 48.24 months (42.48 to 54). Conclusions: We can state that bcl2 is not an independent prognostic factor. Despite the value in other diseases, the determination of bcl-2 by inmunohistochemistry in breast cancer in stages I, II and III at the moment of the diagnosis does not provide any prognostic information.
Safety and efficacy of multipotent adult progenitor cells in acute ischaemic stroke (MASTERS): a randomised, double-blind, placebo-controlled, phase 2 trial
Authors: David C Hess, Lawrence R Wechsler, Wayne M Clark, Sean I Savitz, Gary A Ford, David Chiu, Dileep R Yavagal, Ken Uchino, David S Liebeskind, Alexander P Auchus, Souvik Sen, Cathy A Sila, Jeffrey D Vest, Robert W Mays
Journal: The Lancet Neurology (2017)
A randomised controlled trial of the efficacy and safety of allopurinol dose escalation to achieve target serum urate in people with gout
Authors: Lisa K Stamp, Peter T Chapman, Murray L Barclay, Anne Horne, Christopher Frampton, Paul Tan, Jill Drake, Nicola Dalbeth
Journal: Annals of the Rheumatic Diseases (2017)

Objectives To determine the efficacy and safety of allopurinol dose escalation using a treat-to-target serum urate (SU) approach. Methods A randomised, controlled, parallel-group, comparative clinical trial was undertaken. People with gout receiving at least creatinine clearance (CrCL)-based allopurinol dose for ≥1 month and SU ≥6 mg/dL were recruited. Participants were randomised to continue current dose (control) or allopurinol dose escalation for 12 months. In the dose escalation group, allopurinol was increased monthly until SU was &lt;6 mg/dL. The primary endpoints were reduction in SU and adverse events (AEs). Results 183 participants (93 control, 90 dose escalation) were recruited. At baseline, mean (SD) urate was 7.15 (1.6) mg/dL and allopurinol dose 269 mg/day. 52% had CrCL&lt;60 mL/min. Mean changes in SU at the final visit were −0.34 mg/dL in the control group and −1.5 mg/dL in the dose escalation group (p&lt;0.001) with a mean difference of 1.2 mg/dL (95% CI 0.67 to 1.5, p&lt;0.001). At month 12, 32% of controls and 69% in the dose escalation had SU &lt;6 mg/dL. There were 43 serious AEs in 25 controls and 35 events in 22 dose escalation participants. Only one was considered probably related to allopurinol. Five control and five dose escalation participants died; none was considered allopurinol related. Mild elevations in LFTs were common in both groups, a few moderate increases in gamma glutamyl transferase (GGT) were noted. There was no difference in renal function changes between randomised groups. Conclusions Higher than CrCL-based doses of allopurinol can effectively lower SU to treatment target in most people with gout. Allopurinol dose escalation is well tolerated. Trial registration number: ANZCTR12611000845932 ; Results.
Affect in social media: The role of audience and the presence of contempt in cyberbullying
Authors: Mihaela Cocea
Journal: Behavioral and Brain Sciences (2017)

Abstract Gervais &amp; Fessler's Attitude–Scenario–Emotion (ASE) model is a useful tool for the detection of affect in social media. In this commentary, an addition to the model is proposed – the audience – and its role in the manifestation of affect is discussed using a cyberbullying scenario. The presence of contempt in cyberbullying is also discussed.
EARLY HEMODYNAMIC CHANGES AFTER FETAL AORTIC STENOSIS VALVULOPLASTY ARE ASSOCIATED WITH BIVENTRICULAR CIRCULATION AT BIRTH
Authors: Aaron Prosnitz, Monika Drogosz, Audrey Marshall, Carol Benson, Louise Wilkins-Haug, Wayne Tworetzky, Kevin Friedman
Journal: Journal of the American College of Cardiology (2017)
Association between type 2 diabetes mellitus (T2DM), diabetic therapies and clinical outcomes in patients (pts) with metastatic colorectal cancer (mCRC).
Authors: Natalie Heather Turner, Hui-li Wong, Margaret Lee, Soe Yu Aung, Rajat RAi, Claire Maddison, Louise M. Nott, Desmond Yip, Kortnye Morris, Kathryn M. Field, Jeremy David Shapiro, Suzanne Kosmider, Rachel Wong, Lara Rachel Lipton, Jeremy David Power, Susie Bae, Allan Solomon Zimet, Peter Gibbs
Journal: Journal of Clinical Oncology (2015)

e14637 Background: There is a growing body of epidemiological evidence that T2DM is associated with increased incidence of, and poorer survival in CRC, while metformin use in CRC pts with T2DM has been associated with improved outcomes compared with insulin or sulphonylurea therapy. However, the vast majority of this data relates to early stage CRC. This study evaluates the impact of T2DM and T2DM therapies on clinical outcomes in mCRC pts treated in routine practice. Methods: Pts with mCRC were identified from the multi-site TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) and ACCORD (Australian Comprehensive Cancer Outcomes Research Database) CRC registries. These registries prospectively collect clinical, treatment and outcome data. Clinical and outcome data were compared between pts with and without T2DM. T2DM therapies at the time of diagnosis of mCRC were extracted from chart review. Results: Of 2,214 included pts, 375 (17%) had T2DM, 1,793 (81%) had no T2DM and 46 (2%) had unknown DM status. Median age was higher in T2DM vs. non-DM patients (71 vs 66 years, p<0.01). Overall survival (OS) did not differ significantly between T2DM and non-DM pts (21.5 vs 23.5 months respectively, p=0.37). More detailed clinical characteristics were available for 1497 pts in TRACC, 231 (15%) with T2DM. A higher proportion of T2DM pts had ECOG performance status of ≥2 than non-DM pts (23% vs 17%, p=0.049). There were no other significant differences between T2DM and non-DM pts, including: rate of de novo mCRC, first line chemotherapy, metastasectomy, or treatment intent. T2DM therapy data were available for 302 of 375 pts (81%), with no differences in OS based on type of therapy (Table 1). Conclusions: Contrary to early stage CRC, T2DM was not associated with inferior survival in mCRC pts compared with non-DM pts and metformin use did not appear to positively impact on outcomes. T2DM therapy No. of pts Median OS (months) HR 95%CI P value None (diet-controlled) 84 21.9 - - Metformin 61 27.6 0.88 0.57-1.35 0.55 Sulph (+ insulin in n=1) 35 21.7 1.00 0.60-1.67 1.00 Insulin 35 29.4 0.90 0.56-1.46 0.67 Metformin + sulph/insulin 87 23.0 1.00 0.68-1.47 0.99
Contents, Vol. 30, 1978
Authors: Yujiro Ikemi, Hitoshi Ishikawa, J.R.M. Goyeche, Y. Sasaki, Paula Bram Amar, I. Kaminer, H. Munitz, S. Tyano, H. Wijsenbeek, Hoyle Leigh, Astrid Nøklebye Heiberg, Arvid Heiberg, Harold L. Levitan, Herbert Benson, Fred H. Frankel, Roberta Apfel, Michael D. Daniels, Henry E. Schniewind, John C. Nemiah, Peter E. Sifneos, Karen D. Crassweller, Martha M. Greenwood, Jamie B. Kotch, Patricia A. Arns, Bernard Rosner, Stephen B. Whipple, Donald E. Manning, John G. Flannery, Tetsuya Nakagawa, Shigeyuki Nakano, Shū Mori, Mineyasu Sugita
Journal: Psychotherapy and Psychosomatics (1978)
Short-course androgen suppression therapy prior to brachytherapy for favorable-risk prostate cancer and the risk of all-cause mortality in men with or without preexisting cardiovascular disease
Authors: J. H. Hayes, M. Chen, B. J. Moran, M. H. Braccioforte, D. Dosoretz, S. Salenius, M. Katin, R. Ross, A. V. D’Amico
Journal: Journal of Clinical Oncology (2009)

5066 Background: AST is used to reduce prostate size in men with favorable-risk prostate cancer who have pubic arch interference in order to enable them to undergo prostate brachytherapy. While no disease-specific benefit has been demonstrated to AST in this setting, AST use has been associated with both cardiovascular morbidity and mortality. The Objective is to determine the effect of short-course androgen suppression therapy (AST) prior to brachytherapy on all cause mortality (ACM), stratified by the presence or absence of preexisting cardiovascular disease (CVD). Methods: The study cohort included 12,792 men with previously-untreated low or intermediate risk prostate cancer (PSA &lt; 20 ng/mL; Gleason score 7 or below on initial biopsy; clinical category T2c or below) treated between 1992 and 2005 at one of 21 community-based medical centers in Illinois, Florida, New York, or North Carolina. Men were treated with brachytherapy with or without neoadjuvant AST. Multivariate Cox regression analysis was performed to assess whether significant associations between preexisting CVD and ACM existed adjusting for age, year of treatment and known prostate cancer prognostic factors. Results: After a median follow up of 3.76 years (interquartile range, 2.03 to 5.92 years), 1557 deaths had occurred. The use of neoadjuvant AST was significantly associated with an increased risk of ACM in men with pretreatment CVD (adjusted hazard ratio (AHR) 1.62, 95% CI, 1.40 to 1.87, p &lt; 0.001) but not in men without CVD (AHR 1.06, 95% CI, 0.91 to 1.25, p = 0.5). In men with preexisting CVD, AST use was associated with an increased risk of ACM at 5 years compared to men with CVD who did not use AST (17.5% (95%CI, 15.57% to 19.64%) vs. 14.35% (95%CI, 12.80% to 16.06%), p &lt; 0.0001). Conclusions: Preexisting CVD is associated with an increased risk of death in men with favorable-risk prostate cancer treated with short-course AST prior to brachytherapy. No significant financial relationships to disclose.
Assessment of feasibility and willingness of former heavy smokers to participate in chemoprevention trials to prevent lung cancer.
Authors: Nagi B. Kumar, Gwendolyn P. Quinn, Theresa Crocker, Mark Alexandrow, Jhanelle Elaine Gray, Timothy Estrella, Michael J. Schell, Steve Sutton, Eric B. Haura
Journal: Journal of Clinical Oncology (2012)

e21155 Background: Over 50% of new lung cancers occur in former smokers, who often are seeking strategies to reduce their lung cancer risk. However, recruitment and retention of participants in chemoprevention trials continues to be costly and presents unique challenges. Evaluation of feasibility and knowledge of challenges are critical to inform design and ensure accrual in chemoprevention trials.The study assessed interest and willingness of former heavy smokers to participate in a chemoprevention clinical trial using a botanical agent to prevent lung cancer. Methods: An introductory letter and survey instrument that included the goal of the survey, epidemiological and smoking history, acceptability of trial procedures, perception of lung cancer risk and interest in participating in this trial were mailed to 500 consecutive, former heavy smokers with no cancer from a database of 826 subjects at the Moffitt Cancer Center. Results: 202 (40.4%) men and women returned completed surveys. 98% of respondents were over age 60 and 56% had an undergraduate education or higher. The average years smoked was 40.7 (SD 11.9) pack years. 76% believed there was a 50% chance or greater of developing lung cancer. In response to interest and motivation to participate, 92-96% reported interest in receiving free lung exams, health status monitoring and knowing their lung cancer risk. 88% were interested in being a part of a trial to evaluate a botanical agent for lung cancer prevention. Over 92% of subjects reported a willingness to comply with study requirements, multiple blood draws and trips to the Center, spiral CTs and chest x-rays. Subjects were relatively less enthusiastic (73-79%) about undergoing bronchoscopy, taking multiple study agents and possible assignment to a placebo arm. Conclusions: Our study strongly suggests feasibility, highlights potential challenges and the significant interest and willingness of former smokers to participate in chemoprevention trials.
EARLY DETECTION OF CARDIAC INVOLVEMENT IN SARCOIDOSIS WITH 2-DIMENSIONAL SPECKLE-TRACKING ECHOCARDIOGRAPHY
Authors: Elie Dan Schouver, Pamela Moceri, Denis Doyen, Nathalie Tieulie, Viviane Queyrel, Delphine Baudouy, Pierre Cerboni, Sylvie Leroy, Emile Ferrari
Journal: Journal of the American College of Cardiology (2017)
TREND AND OUTCOMES OF INFECTIVE ENDOCARDITIS TREATED WITH SURGICAL VALVULAR REPLACEMENT INSIGHT FROM THE NATIONWIDE INPATIENT SAMPLE
Authors: Sami Aljohani, Fahad Alqahtani, Ahmed Almustafa, Allison Lastinger, Ashwin Bhirud, MohammadAkram Kawsara, Chalak Berzingi, Sameer Raina, Mohamad Alkhouli
Journal: Journal of the American College of Cardiology (2017)