tbuckley/cabot-search huggingface dataset:
Abstract 1700: A combination of two tropical spice compounds potentiates chemotherapy response in castration-resistant prostate cancer cells
Authors: Taaha A. Mendha, Shamaladevi Nagarajarao, Balakrisha L. Lokeshwar
Journal: Cancer Research (2014)

Abstract Introduction: Patients with castration resistant advanced prostate cancer (CRPC) respond poorly to potent chemotherapeutic drugs (e.g., Docetaxel or Mitoxantrone) with survival advantages that last less than 4 months. Since chemotherapy itself has morbidity in the elderly patients, adding another such drug is unlikely to improve the outcome. We investigated the potential therapeutic benefits of treating CRPC with a combination of two natural dietary anti-proliferative compounds: Curcumin and Piperine. They are derived from the tropical spices, turmeric and black pepper, respectively. Both are orally bioavailable and can be consumed over a long period of time. Materials and methods: The cytotoxicity of Curcumin, Piperine, and Docetaxel were individually tested on a CRPC cell line PC-3, which was incubated for 48 hours or 72 hours. Cytotoxicity was evaluated by cell counting, a colorimetric assay and by clonogenic survival, colony-formation assay. Enhancement of Docetaxel cytotoxicity by natural compounds was evaluated by treating cells with these compounds 24 hours before adding Docetaxel or with co-incubation. The potential mechanism of cytotoxicity was examined by an apoptosis assay and changes in cell cycle phase-fractions. The efficacy of the combination was evaluated by Isobologram analysis and ANOVA. Results: All three drugs tested on PC-3 showed cytotoxicity, Docetaxel was the most cytotoxic (IC50∼ 25 nM) and Piperine was the least cytotoxic (IC50∼ 100 μM). Curcumin alone was significantly cytotoxic to PC-3 cells at 10 μM but it enhanced the cytotoxicity of Docetaxel. Piperine, when combined with Curcumin or Docetaxel, significantly increased the cytotoxicity by 50%. Prior exposure to Piperine resulted in enhanced cytotoxicity of Docetaxel and Curcumin more than when in co-incubation. The increased cytotoxicity in combination therapy was mainly due to increased apoptotic activity. Conclusion: This study demonstrated that combining diet-derived antiproliferatinve compounds with a chemotherapy drug can potentially enhance tumoricidal activity and therefore, potentially reduce morbidity and mortality of patients with CRPC. Pretreatment with dietary compounds could potentially enhance subsequent treatment with chemotherapy agents. Citation Format: Taaha A. Mendha, Shamaladevi Nagarajarao, Balakrisha L. Lokeshwar. A combination of two tropical spice compounds potentiates chemotherapy response in castration-resistant prostate cancer cells. [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 1700. doi:10.1158/1538-7445.AM2014-1700
Abstract 18226: Finding the Ideal Biomaterial for Aortic Valve Repair
Authors: Hadi D Toeg, Ovais Abessi, Talal Al-Atassi, Laurent de Kerchove, Gebrine El-Khoury, Michel Labrosse, Munir Boodhwani
Journal: Circulation (2013)

Objectives: Cusp replacement in aortic valve repair (AVr) is associated with increased long-term repair failure. We measured hemodynamic and biomaterial properties after porcine AVr with 4 types of clinically relevant biomaterials to ascertain which material(s) would be best suited for repair. Methods: Porcine aortic roots with intact aortic valves were placed in a left heart simulator mounted with a high-speed camera for baseline valve assessment. The non-coronary cusp (NCC) was excised and replaced with autologous porcine pericardium (APP), glutaraldehyde-fixed bovine pericardial patch (BPP; Synovis™), extracelluar matrix scaffold (CorMatrix™), or collagen-impregnated Dacron (HEMASHIELD™). Biomaterial properties, along with St. Jude Medical™ Pericardial Patch with EnCapTM Technology (SJM), were determined and finite element modeling of the aortic valve and root complex were constructed to determine hemodynamic characteristics and leaflet stresses. Results: Post-repair geometric orifice areas were significantly reduced in the HEMASHIELD™ (5.06 cm2 [4.24-5.73];P&lt;0.05), and CorMatrix™ ( 5.27 cm2 [4.57-5.56]; P=0.0001) groups when compared to unrepaired valves (6.08 cm2 [5.82-6.83]). Finite element modeling of biomaterials displayed differences in percent changes in total Von Mises stress for both repaired (NCC) and non-repaired left and right cusps with SJM (+4%,+24%) and APP (+5,+26%) having lower percent changes than BPP (+12%,+27%), HEMASHIELD™ (+30%,+9%), and CorMatrix™ (+13%,+32%) when compared to unrepaired valve stresses (Table 1). Conclusions: Due to increased stresses found in bovine pericardial patch, HEMASHIELD™, and CorMatrix™ groups, these biomaterials may be associated with late repair failure in AVr. Finally, autologous porcine pericardium and St. Jude Medical™ Pericadial Patch have the closest profile to normal aortic valves; therefore, use of either biomaterial may be best suited.
Effects of ulinastatin in treatment of invasive candidiasis
Authors: Shunwei Huang, Xiaoyue Li, Xiangdong Guan
Journal: European Respiratory Journal (2013)

Objective To investigate the effects and mechanism of Ulinastatin (UTI) combined with antifungal agents in treatment of Invasive Candidiasis (IC). Method Sixty Kunming mice were randomly assigned to control group, low-dose group and high-dose group (each n=20). The model of IC was reproduced by intraperitoneal injection of White monilial suspension after CTX pretreatment. Mice in control group were treated with antifungal agents. Mice in low-dose group and high-dose group were treated with UTI (104U/kg or 5×104U/kg)and antifungal agents. Survival rate, cytokine in liver tissue and blood lymphocyte subsets were compared among these groups. Results There was significant difference in survival rate between control group and high-dose group [30% (6/20) vs. 70% (14/20), p =0.011]. There was no significant difference in survival rate between other groups ( p >0.05). There were significant differences in IL-10 among three groups [94.1±9.11 vs. 93.9±4.91 vs. 82.5±14.0, p <0.05]. There were significant differences in CD3+ rate, CD4+ rate and CD8+rate between control group and high-dose group [22.5±5.24 vs. 26.4±3.63, 14.6±1.26 vs. 16.7±2.19, 6.60±1.51 vs. 4.50±0.97, p <0.05]. There were significant differences in CD4+/CD8+ rate among three groups [2.32±0.59 vs. 2.90±0.87 vs. 3.82±0.82, p <0.05]. Conclusions High-dose UTI could improve survival rate in mice with IC through improving cellular immune and reducing immunosuppression.
Late-breaking abstract: Efficacy and safety of once-daily QVA149 compared with twice-daily salmeterol/fluticasone combination (SFC) in patients with COPD: The LANTERN study
Authors: Nanshan Zhong, Changzheng Wang, Xiangdong Zhou, Nuofu Zhang, Francesco Patalano, Michael Humphries, Linda Wang, Donald Banerji
Journal: European Respiratory Journal (2014)

Background   In a head to head comparison, the LANTERN study evaluated QVA149 once daily (LABA/LAMA) versus SFC twice daily (LABA/ICS) in patients (pts) with moderate to severe COPD.   Methods   In this double-blind, double-dummy, parallel-group study, 744 pts with moderate to severe COPD and who may have had a recent history of exacerbation (post-bronchodilator FEV 1  ≥30% and  1  at Wk 26. Other endpoints: FEV 1  AUC 0-4hr , TDI, SGRQ, exacerbations and safety.   Results   Overall 676 pts (90.9%) completed the study. At Wk 26, QVA149 demonstrated NI followed by statistically significant superiority to SFC for trough FEV 1  (treatment difference (Δ) =75mL, 95% confidence interval (CI): 44, 107mL; p 1  AUC 0-4h  at Wk 26 vs SFC (Δ=122mL; p   Conclusion   QVA149 was superior in bronchodilation and rate of exacerbations versus SFC and was similar in pt-reported outcomes. These findings support the use of LABA/LAMA combination over LABA/ICS in moderate-to-severe COPD pts with or without recent exacerbations.
Abstract 107: Chest Compression Induced Ventricular Activation, a Novel Phenomenon, During Cardiopulmonary Resuscitation
Authors: Nienke Hoogkamp, Ruud W M Pijls, Anton P M Gorgels
Journal: Circulation (2014)

Objectives:  To study chest compressions induced electrical ventricular activation, termed mechano-electrical coupling (MEC), during cardiopulmonary resuscitation (CPR).   Methods:  All 102 automated external defibrillators (AED) recordings by non-professional CPR providers from our Utstein style registry of out of hospital resuscitations in Dutch province Limburg between April 2011 and April 2014 were studied regarding chest compressions, organized electrical activity and their mutual relation.   Results:  AED population: Mean age was 65 (σ=14.1) years, 75.5% were male, 36.3% had a cardiovascular history. In 73.5% the cause of the arrest was cardiac, in 37.3% by an acute coronary syndrome. Survival to hospital discharge was 34.7%, resp. 44.0% if the cause was cardiac.  AED recordings: Mean duration was 06 minutes and 28 seconds (σ=05:37), first rhythm, was VF in 69%, last monitored rhythm was organized in 50.9%.  During MEC a previously slow intrinsic ventricular rhythm, increased to the frequency of chest compressions. MEC was seen in 15%(n=15) of cases in 30 episodes, during 739 chest compressions, with a mean duration of 14 seconds (σ=8.5) and at a mean compression rate of 122 (σ=19,9)/min. Refibrillation was present in 50% of all patients, spontaneous in 43%, failed shock in 26% or during chest compressions in 31%, however it was not observed during episodes of continuous one-to-one MEC.  No difference was seen in survival to discharge, between patients with and without MEC.   Conclusion:  During CPR chest compressions may lead to one to one electrical activation of the ventricles.  MEC may be beneficial: synchronized electrical activity and mechanical compressions may increase stroke volume, and chest compression induced VF may be prevented. Research in larger populations has to be performed as to the incidence of and conditions leading to MEC, such as CPR and patient related variables.
Abstract 13873: Quantitative Characteristics of Left Ventricular Vortex Flow in the Short and Long Axis Views by High Frame Rate Echocardiographic Particle Image Velocimetry
Authors: Haruhiko Abe, Kasumi Masuda, Toshihiko Asanuma, Hikaru Koriyama, Yukihiro Koretsune, Hideo Kusuoka, Satoshi Nakatani
Journal: Circulation (2014)

Background: Vortex flow in the left ventricle (LV) has three-dimensional structure and plays an important role in avoiding excessive dissipation of energy. However, quantitative characteristics of long and short axis (LAX and SAX) vortex flow have not been elucidated. Echocardiographic particle image velocimetry (Echo-PIV) is an emerging technique to evaluate instantaneous vortical flow inside the LV. However, it has a limitation of underestimation of high velocities due to limited frame rate. Moreover, previous investigations have mainly focused on vortex from LAX view. Therefore, we used high frame rate Echo-PIV to quantitate vortex flow in SAX as well as in LAX views to understand characteristics of vortex three-dimensionally. Methods: Echocardiographic contrast images of the LV SAX and LAX were acquired from 8 open-chest healthy dogs. The acquisition frame rate was 135 frames per second and the contrast bubbles density was optimized for blood flow analysis. Echo-PIV analysis was performed off-line by using commercially available software and vorticity data were calculated in the region of interest (ROI) throughout the cardiac cycle. ROI was manually placed on the vortex. Vortex strength was defined as the averaged vorticity within the ROI. Results: In SAX, counterclockwise vortex was seen near the anterior wall, and in LAX clockwise vortex was seen in the anterior mid-ventricle. Both in SAX and LAX views, vortex strength showed significant phasic variations being largest in isovolumic contraction (vortex strength, SAX 9.2±2.3/s, p&lt;0.001; LAX -12.0±2.4/s, p&lt;0.001), and smallest in isovolumic relaxation (SAX -0.8±0.8/s, p&lt;0.001; LAX -1.9±1.9/s, p&lt;0.001). Conclusion: High frame rate Echo-PIV successfully demonstrated a complicated pattern of intracardiac vortex with phasic variation of its strength throughout a cardiac cycle in both SAX and LAX. This method may be a useful tool to assess physiological role of vortex in the flow dynamics.
Global Analysis of Altered Gene Expressions during the Process of Esophageal Squamous Cell Carcinogenesis in the Rat: A Study Combined with a Laser Microdissection and a cDNA Microarray
Authors: Koujiro Nishida, Shinji Mine, Tohru Utsunomiya, Hiroshi Inoue, Masahiro Okamoto, Harushi Udagawa, Taizo Hanai, Masaki Mori
Journal: Cancer Research (2005)

The genetic alterations that occur during esophageal tumorigenesis have yet to be determined. We previously established a Wister rat carcinogenesis model of esophageal squamous cell carcinoma. To understand more about the molecular mechanisms during carcinogenesis, we produced esophageal neoplastic lesions by administering N-amyl-N-methylnitrosamine and 12-O-tetradecanoylphorbol-13-acetate to rats. We used laser microdissection to specifically isolate the cells from the normal epithelium, papilloma, dysplasia, and invasive carcinoma. Using a cDNA microarray representing 14,815 clones, we then analyzed the gene expression profiles for each esophageal lesion. The number of differentially expressed genes compared with the normal control dramatically increased in a step-by-step fashion from normal epithelium (1,151 +/- 119 genes) to papilloma (1,899 +/- 543 genes), dysplasia (1,991 +/- 193 genes), and invasive carcinoma (2,756 +/- 87 genes). A hierarchical clustering analysis showed that the three stages of normal epithelium, dysplasia (papilloma), and invasive carcinoma could be clearly classified, whereas the gene expression patterns of papilloma and dysplasia were indistinguishable. Using the Fisher criterion, we also identified 50 genes whose expression level had either significantly increased or decreased in a step-by-step manner from the normal epithelium to dysplasia and then finally to invasive carcinoma. Many of these genes were not previously known to be associated with esophageal carcinogenesis. The present findings in our rat model thus seem to provide us with a better understanding of the molecular alterations that occur during esophageal carcinogenesis and hopefully will also help lead to the development of novel diagnostic and therapeutic targets.
Abstract 17534: HIV-Infected Patients Exhibit a Worse Cardiovascular Risk Profile After a First Episode of Acute Coronary Syndrome
Authors: Franck Boccara, Murielle Mary-Krause, Emmanuel Teiger, Sylvie Lang, Pascal Lim, Karim Wahbi, Farzin Beygui, Olivier Milleron, Philippe Gabriel Steg, Christian Funck-Brentano, Michel Slama, Pierre-Marie Girard, Dominique Costagliola, Ariel Cohen
Journal: Circulation (2011)

Purpose: The PACS-HIV study was designed to determine the 3-year prognosis of acute coronary syndrome (ACS) in HIV-infected patients (HIV+) as compared to HIV- in a prospective observational study. We report the cardiovascular risk profile after the index ACS. Methods: We enrolled 103 HIV-infected and 195 HIV-uninfected patients with a first episode of ACS matched for age (± 5 years), sex, and type of ACS. During follow up, cardiovascular risk factors including lipid parameters, tobacco consumption were collected. Univariate conditional logistic regression was used to compare variables and stratified multivariate Cox models were performed. Results: The mean age at enrolment was 49.0 ± 9.4 years and 94% were men. At admission, coronary risk factors were well balanced between the 2 groups except for a higher rate of illicit drug used and hypertriglyceridaemia in the HIV+ group. At 3-year follow up, HIV+ patient exert a higher rate of recurrent ACS as compared with HIV- patients (univariate HR 3.4; 95% CI [1.3-8.8]). At long term, HIV+ exhibit a worse cardiovascular risk profile with more smokers and worse atherogenic lipid profile (Table). Incident cases of hypertension and diabetes tend to be higher in the HIV+ group (16.2/1000 persons per year (PY) vs 9.1/1000 PY, RR (HIV+ / HIV-)=1.8, IC 95% =[0.4-7.1] 41.0/1000 PY vs 21.9/1000PY, RR (HIV+ / HIV-)=1.9, IC 95% =[0.8-4.3], respectively). Stratified multivariable Cox model showed that HIV status, total cholesterol and LDLc were associated with the recurrence of ACS (Table). Conclusions: At long-term follow-up after ACS, HIV+ exhibit higher residual cardiovascular risk. HIV infection and atherogenic lipid profile were associated with an increased risk of ACS. Secondary prevention should focus on smoking cessation and strict LDL goal in HIV+. Table. Cardiovascular risk factors at 3-year follow Multivariate analysis associated with increased risk of recurrent ACS Values expressed as n (%) , *time-dependent covariates
Haplotype on GTP-Cyclohydrolase I Gene, Reveals a Novel Role of Tetrahydrobiopterin as a Defense Mechanism Against Inflammation-Induced Endothelial Dysfunction in Human Atherosclerosis
Authors: Charalambos Antoniades, Alexios S Antonopoulos, Matthew Neville, Michael Demosthenous, Kyriakoula Marinou, Dimitris Tousoulis, Marina Toutouza, Christodoulos Stefanadis, Fredrik Karpe, Keith M Channon
Journal: Circulation (2011)
Differences in the Selective Antitumor Effects of 4-Deoxypyridoxine and Dietary Pyridoxine Deficiency
Authors: E. Mihich, C. A. Nichol
Journal: Cancer Research (1965)

The effects of 4-deoxypyridoxine were contrasted with those of prolonged periods of dietary pyridoxine deficiency using Sarcoma 180 (S-180) as a test system. The drug was inactive against this tumor in animals fed complete diets. The antimetabolite markedly inhibited the growth of S-180 in mice fed a vitamin B6-deficient diet from the day of tumor implantation. Under such dietary conditions, which alone did not restrict the growth of the tumor, the drug was effective at levels as low as 1 mg/100 gm of diet. The inhibition of tumor growth caused by 4-deoxypyridoxine was not followed by regression of the tumor. The drug prevented the complete regression of the tumor, which occurs in mice depleted of the vitamin from the 14th day prior to implantation, only when it was given during the week preceding, or that following, the day of implantation. 4-Deoxypyridoxine did not exert such an effect when it was given during the 2d week of tumor growth. The prevention of tumor regression by 4-deoxypyridoxine was consistent with the marked depression of lymphoid tissues exerted by this drug. The antimetabolite inhibited the growth of S-180/B6, a subline capable of growing in pyridoxine-depleted mice, and of S-180 ascites implanted subcutaneously, in contrast to the lack of effect of the dietary pyridoxine depletion on these tumors.

The data reported herein indicate that pyridoxine antagonists differ among themselves with reference to their selective actions in the S-180 system. Isonicotinic acid hydrazide alone was not very active either in inhibiting the growth of S-180 or in preventing its regression in the deficient mice. Yet this compound markedly increased the effects of 4-deoxypyridoxine when given in combination. Another antagonist of vitamin B6, thiosemicarbazide, was very effective against S-180 regardless of the dietary condition and caused complete tumor regression. The incidence of regression was increased when thiosemicarbazide was administered to mice which were fed the deficient diet.
Pharmacogenomics
Authors: W. Sadee
Journal: BMJ (1999)

Herpes genitalis is an infection associated with considerable morbidity. Acyclovir, though effective, must be taken daily to prevent recurrences. The effects of interferon on this infection were therefore investigated. In a randomised double blind study, 31 patients with first episodes of genital herpes infection were studied to assess the effect of interferon on the presenting episode and on recurrences. Interferon (5 X 10(6) IU) was administered once daily subcutaneously during a five day "treatment" period followed by a three month "maintenance" period (1 X 10(6) IU three times weekly). Interferon had no effect on first episode herpetic attacks. During interferon administration women showed a trend towards reduced healing time and viral shedding in recurrences, but the differences were not significant and no effect was noted in women after administration of interferon. Interferon reduced assessed healing time and viral shedding in recurrences, however, in men (p = 0.05) during interferon administration, and this continued as a trend after treatment.
Outcome for patients who relapse after allogeneic bone marrow transplantation for chronic myeloid leukemia. Chronic Leukemia Working Party. European Bone Marrow Transplantation Group
Authors: W Arcese, JM Goldman, E D'Arcangelo, A Schattenberg, A Nardi, JF Apperley, F Frassoni, F Aversa, HG Prentice, P Ljungman
Journal: Blood (1993)
Are part time doctors better doctors?
Authors: I. Goldberg, R. Hornung, A. Lipp, C. Sahleen-Veasey, L. Morrison, C. Manning
Journal: BMJ (1998)

Many climate change scientists do not agree that global warming is happeningEditor-The apocalyptic tone that Smith adopted in relation to the environment bears little relation to reality. 1 In his editorial Smith asserts, "virtually all scientists agree that global warming is happening."Global warming is now joining the list of "what everyone knows."Whether most scientists outside climatology believe that global warming is happening is less relevant than whether the climatologists do.A letter signed by over 50 leading members of the American Meteorological Society warned about the policies promoted by environmental pressure groups."The policy initiatives derive from highly uncertain scientific theories.They are based on the unsupported assumption that catastrophic global warming follows from the burning of fossil fuel and requires immediate action.We do not agree." 2 Those who have signed the letter represent the overwhelming majority of climate change scientists in the United States, of whom there are about 60.McMichael and Haines quote the 1995 report of the Intergovernmental Panel on Climate Change (IPCC), which is widely believed to "prove" that climate change induced by humans has occurred. 3 The original draft document did not say this.What happened was that the policymakers' summary (which became the "take home message" for politicians) altered the conclusions of the scientists.This led Dr Frederick Seitz, former head of the United States National Academy of Sciences, to write, "In more than sixty years as a member of the American scientific community . . .I have never witnessed a more disturbing corruption of the peer-review process than the events that led to this IPCC report." 4 Policymaking should be guided by proved fact, not speculation.Most members of the Intergovernmental Panel on Climate Change believe that current climate models do not accurately portray the atmosphereocean system.Measurements made by means of satellites show no global warming but a cooling of 0.13°C between 1979 and 1994. 5Furthermore, since the theory of global warming assumes maximum warming at the poles, why have average temperatures in the Arctic dropped by 0.88°C over the past 50 years? 5