bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal Variability of Ventricular Arrhythmias in Boxer Dogs with Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Scansen B.A. , Meurs K.M. , Spier A.W. , Koplitz S. , Baumwart R.D. 
Published: August 2009

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is prevalent in the Boxer. There is little information on the temporal variability of ventricular arrhythmias within affected dogs.Objective: To evaluate ambulatory electrocardiograms (AECG) from Boxers with ARVC for hourly variation in premature ventricular complexes (PVC) and heart rate (HR).Animals: One hundred and sixty‐two Boxer dogs with ARVC.Methods: Retrospective, observational study of 1,181 AECGs collected from Boxer dogs at The Ohio State University from 1997 to 2004 was evaluated. The proportion of depolarizations that were PVCs was compared across each hour of the day, during six 4‐hour periods of day, to the time after AECG application, and to the maximum and minimum HR.Results: A lower proportion of PVCs was noted during early morning (midnight to 0400 hours) as compared with the morning (0800–1200 hours) and late (1600–2000 hours) afternoon (P= .012). There was no increase in PVC proportion in the 1st hour after AECG application as compared with all other hours of the day (P= .06). There was poor correlation between maximum (ρ= 0.19) and minimum (ρ= 0.12) HR and PVC proportion.Conclusions and Clinical Importance: The likelihood of PVC occurrence in Boxer dogs with ARVC was relatively constant throughout the day, although slightly greater during the hours of 0800–1200 and 1600–2000. A biologically important correlation with HR was not apparent. The role of autonomic activity in the modulation of electrical instability in the Boxer with ARVC requires further study.
Effect of Transvenous Electrical Cardioversion on Plasma Cardiac Troponin I Concentrations in Horses with Atrial Fibrillation
Authors: Jesty S.A. , Kraus M. , Gelzer A. , Rishniw M. , Moïse N.S. 
Published: August 2009

Background:Whether electrical cardioversion of cardiac arrhythmias results in cardiomyocyte damage is unknown.Objective:To describe effect of transvenous electrical cardioversion (TVEC) on plasma cardiac troponin I (cTnI) concentration in horses.Animals:All horses presented to the Cornell University Hospital for Animals for cardioversion of atrial fibrillation between May 2006 and October 2008 were eligible for inclusion in the study. Owners of 14 horses elected for TVEC and each horse was then enrolled (16 procedures).Methods:Prospective observational study measuring concentrations of plasma cTnI before and after TVEC.Results:Median cTnI concentration increased from 0.045 ng/mL at baseline (range 0.0–0.20 ng/mL) to 0.11 ng/mL after TVEC (range 0.0–3.73 ng/mL) (P= .036). This increase was not associated with the number of shocks delivered, maximal energy delivered, cumulative energy delivered, chronicity of atrial fibrillation before cardioversion, or positioning of the pulmonary artery catheter.Conclusions:The increase in cTnI is unlikely to be clinically important. The increase might be correlated with persistent atrial dysfunction after TVEC, suggesting that a longer convalescent period after the procedure could be warranted.
Effect of Experimental Hypothyroidism on Glomerular Filtration Rate and Plasma Creatinine Concentration in Dogs
Authors: Panciera D.L. , Lefebvre H.P. 
Published: August 2009

Background:Hypothyroidism affects renal function in a manner opposite the effects of hyperthyroidism.Objective:To evaluate the effects of experimentally induced hypothyroidism on glomerular filtration rate (GFR) and basal plasma creatinine concentration in dogs.Animals:Sixteen anestrous, female dogs.Methods:Hypothyroidism was induced by administration of131I in 8 dogs, and 8 healthy euthyroid dogs acted as controls. Exogenous plasma creatinine clearance (an estimate of GFR) was measured in all dogs before (control period) and 43–50 weeks after induction of hypothyroidism (posttreatment period). Other pharmacokinetic parameters of creatinine were also determined.Results:No significant difference was observed for basal plasma creatinine concentration and creatinine clearance between control and hypothyroid dogs in the control period. In the posttreatment period, mean ± SD creatinine clearance in the hypothyroid group (2.13 ± 0.48 mL/min/kg) was lower (P< .001) than that of the control group (3.20 ± 0.42 mL/kg/min). Nevertheless, basal plasma creatinine concentrations were not significantly different between the hypothyroid and control groups (0.74 ± 0.18 versus 0.70 ± 0.08 mg/dL, respectively) because endogenous production of creatinine was decreased in hypothyroid dogs (22 ± 3 versus 32 ± 5 mg/kg/d,P=.001).Conclusion and Clinical Importance:Hypothyroidism causes a substantial decrease in GFR without altering plasma creatinine concentrations, indicating that GFR evaluation is needed to identify renal dysfunction in such patients.
A MECHANISM FOR FILTERING DISTRACTORS FOR DOODLE PASSWORDS
Authors: POET RON , RENAUD KAREN 
Published: August 2009

Graphical authentication holds some potential as an alternative to the ubiquitous password. Graphical authentication mechanisms typically present users with one or more challenge sets composed of a number of images: one target image surrounded by distractor images. Unfortunately, this means it tends to be more time-consuming than password entry and to alleviate this, we need to streamline the process as much as possible to maximize efficiency. The distractors must be chosen with care so as to ensure that users do not become confused by similarities with the target image. It is especially challenging to achieve this filtering with minimalist image types, such as hand-drawn doodles. This paper explores the issues related to filtering the distractor images used in graphical authentication mechanisms using minimalist images. We present an algorithm for automatically classifying minimalist images in terms of visual similarity. The principles outlined here can also be used to assess the similarity of other minimalist image types such as signatures and handwritten numerals.
Inhibition of Activator Protein-1 by Sulforaphane Involves Interaction with Cysteine in the cFos DNA-Binding Domain: Implications for Chemoprevention of UVB-Induced Skin Cancer
Authors: Dickinson Sally E. , Melton Tania F. , Olson Erik R. , Zhang Jian , Saboda Kathylynn , Bowden G. Timothy 
Published: August 2009

Abstract
Sulforaphane is an isothiocyanate derived from cruciferous vegetables that has been linked to decreased risk of certain cancers. Although the role of sulforaphane in the induction of the transcription factor Nrf2 has been studied extensively, there is also evidence that inhibition of the transcription factor activator protein-1 (AP-1) may contribute to the chemopreventive properties of this compound. In this study, we show for the first time that sulforaphane is effective at reducing the multiplicity and tumor burden of UVB-induced squamous cell carcinoma in a mouse model using cotreatment with the compound and the carcinogen. We also show that sulforaphane pretreatment is able to reduce the activity of AP-1 luciferase in the skin of transgenic mice after UVB. Chromatin immunoprecipitation analysis verified that a main constituent of the AP-1 dimer, cFos, is inhibited from binding to the AP-1 DNA binding site by sulforaphane. Electrophoretic mobility shift assay analysis of nuclear proteins also shows that sulforaphane and diamide, both known to react with cysteine amino acids, are effective at inhibiting AP-1 from binding to its response element. Using truncated recombinant cFos and cJun, we show that mutation of critical cysteines in the DNA-binding domain of these proteins (Cys154 in cFos and Cys272 in cJun) results in loss of sensitivity to both sulforaphane and diamide in electrophoretic mobility shift assay analysis. Together, these data indicate that inhibition of AP-1 activity may be an important molecular mechanism in chemoprevention of squamous cell carcinoma by sulforaphane. [Cancer Res 2009;69(17):7103–10]
Consensus Recommendations to Accelerate Clinical Trials for Neurofibromatosis Type 2
Authors: Evans D. Gareth , Kalamarides Michel , Hunter-Schaedle Kim , Blakeley Jaishri , Allen Jeffrey , Babovic-Vuskanovic Dusica , Belzberg Allan , Bollag Gideon , Chen Ruihong , DiTomaso Emmanuelle , Golfinos John , Harris Gordon , Jacob Abraham , Kalpana Ganjam , Karajannis Matthias , Korf Bruce , Kurzrock Razelle , Law Meng , McClatchey Andrea , Packer Roger , Roehm Pamela , Rubenstein Allan , Slattery William , Tonsgard James H. , Welling D. Bradley , Widemann Brigitte , Yohay Kaleb , Giovannini Marco 
Published: August 2009

Abstract
Purpose: Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder associated primarily with bilateral schwannomas seen on the superior vestibular branches of the eighth cranial nerves. Significant morbidity can result from surgical treatment of these tumors. Meningiomas, ependymomas, and other benign central nervous system tumors are also common in NF2. The lack of effective treatments for NF2 marks an unmet medical need.
Experimental Design: Here, we provide recommendations from a workshop, cochaired by Drs. D. Gareth Evans and Marco Giovannini, of 36 international researchers, physicians, representatives of the biotechnology industry, and patient advocates on how to accelerate progress toward NF2 clinical trials.
Results: Workshop participants reached a consensus that, based on current knowledge, the time is right to plan and implement NF2 clinical trials. Obstacles impeding NF2 clinical trials and how to address them were discussed, as well as the candidate therapeutic pipeline for NF2.
Conclusions: Both phase 0 and phase II NF2 trials are near-term options for NF2 clinical trials. The number of NF2 patients in the population remains limited, and successful recruitment will require ongoing collaboration efforts between NF2 clinics. (Clin Cancer Res 2009;15(16):5032–9)
Evaluation of a 1,4,7,10-Tetraazacyclododecane-1,4,7,10-Tetraacetic Acid–Conjugated Bombesin-Based Radioantagonist for the Labeling with Single-Photon Emission Computed Tomography, Positron Emission Tomography, and Therapeutic Radionuclides
Authors: Mansi Rosalba , Wang Xuejuan , Forrer Flavio , Kneifel Stefan , Tamma Maria-Luisa , Waser Beatrice , Cescato Renzo , Reubi Jean Claude , Maecke Helmut R. 
Published: August 2009

AbstractPurpose: G protein–coupled receptor agonists are being used as radiolabeled vectors for in vivo localization and therapy of tumors. Recently, somatostatin-based antagonists were shown to be superior to agonists. Here, we compare the new [111In/68Ga]-labeled bombesin-based antagonist RM1 with the agonist [111In]-AMBA for targeting the gastrin-releasing peptide receptor (GRPR).Experimental Design: IC50, Kd values, and antagonist potency were determined using PC-3 and HEK-GRPR cells. Biodistribution and imaging studies were done in nude mice transplanted with the PC-3 tumor. The antagonist potency was assessed by evaluating the effects on calcium release and on receptor internalization monitored by immunofluorescence microscopy.Results: The IC50 value of [natIn]-RM1 was 14 ± 3.4 nmol/L. [nat/111In]-RM1 was found to bind to the GRPR with a Kd of 8.5 ± 2.7 nmol/L compared with a Kd of 0.6 ± 0.3 nmol/L of [111In]-AMBA. A higher maximum number of binding site value was observed for [111In]-RM1 (2.4 ± 0.2 nmol/L) compared with [111In]-AMBA (0.7 ± 0.1 nmol/L). [natLu]-AMBA is a potent agonist in the immunofluorescence-based internalization assay, whereas [natIn]-RM1 is inactive alone but efficiently antagonizes the bombesin effect. These data are confirmed by the calcium release assay. The pharmacokinetics showed a superiority of the radioantagonist with regard to the high tumor uptake (13.4 ± 0.8% IA/g versus 3.69 ± 0.75% IA/g at 4 hours after injection. as well as to all tumor-to-normal tissue ratios.Conclusion: Despite their relatively low GRPR affinity, the antagonists [111In/68Ga]-RM1 showed superior targeting properties compared with [111In]-AMBA. As found for somatostatin receptor–targeting radiopeptides, GRP-based radioantagonists seem to be superior to radioagonists for in vivo imaging and potentially also for targeted radiotherapy of GRPR-positive tumors. (Clin Cancer Res 2009;15(16):5240–9)
Antiangiogenic and Antitumor Activity of 6-(2-Aminoethyl)Amino-5-Chlorouracil, a Novel Small-Molecule Inhibitor of Thymidine Phosphorylase, in Combination with the Vascular Endothelial Growth Factor-Trap
Authors: Lu Haiyan , Klein Robert S. , Schwartz Edward L. 
Published: August 2009

Abstract
Purpose: Tumors produce multiple proangiogenic factors, making it unlikely that agents targeting a single angiogenic pathway will be sufficient to treat the spectrum of tumors that occur clinically. Platelet-derived endothelial cell growth factor has angiogenic activity in vitro and in vivo and is overexpressed in most human cancers, where its expression has been correlated with increased microvessel density, more aggressive tumors, and poorer patient prognosis. Platelet-derived endothelial cell growth factor is identical to the enzyme thymidine phosphorylase (TP), and unlike other angiogenic factors, the proangiogenic actions of TP are dependent on its enzyme activity.
Experimental Design: A potent and specific small-molecule inhibitor of the catalytic activity of TP, 6-(2-aminoethyl)amino-5-chlorouracil (AEAC), was tested for antiangiogenic and antitumor activity in human cancer xenografts in vivo.
Results: Oral administration of AEAC caused 40% to 50% reductions in the growth of A549 non–small cell lung cancer and PANC-1 pancreatic cancer xenografts, but it was not active against a second pancreatic tumor, BxPC-3. AEAC reduced the microvessel density in the tumors, providing evidence for an antiangiogenic action. Equal or better activity was seen when the mice were treated with the vascular endothelial growth factor (VEGF)-Trap, a soluble VEGF decoy receptor, and the combination of AEAC and VEGF-Trap produced additive antitumor activity that was significantly greater than the VEGF-Trap alone. In the A549 tumors, the combination produced tumor regressions.
Conclusion: These studies show antitumor activity for a drug targeting TP and suggest that inhibitors of TP could be used to augment the clinical efficacy of drugs targeting the VEGF pathway. (Clin Cancer Res 2009;15(16):5136–44)
Visualizing Implanted Tumors in Mice with Magnetic Resonance Imaging Using Magnetotactic Bacteria
Authors: Benoit Michael R. , Mayer Dirk , Barak Yoram , Chen Ian Y. , Hu Wei , Cheng Zhen , Wang Shan X. , Spielman Daniel M. , Gambhir Sanjiv S. , Matin A. 
Published: August 2009

Abstract
Purpose: To determine if magnetotactic bacteria can target tumors in mice and provide positive contrast for visualization using magnetic resonance imaging.
Experimental Design: The ability of the magnetotactic bacterium, Magnetospirillum magneticum AMB-1 (referred to from here as AMB-1), to confer positive magnetic resonance imaging contrast was determined in vitro and in vivo. For the latter studies, AMB-1 were injected either i.t. or i.v. Bacterial growth conditions were manipulated to produce small (∼25-nm diameter) magnetite particles, which were observed using transmission electron microscopy. Tumor targeting was confirmed using 64Cu-labeled bacteria and positron emission tomography and by determination of viable cell counts recovered from different organs and the tumor.
Results: We show that AMB-1 bacteria with small magnetite particles generate T1-weighted positive contrast, enhancing in vivo visualization by magnetic resonance imaging. Following i.v. injection of 64Cu-labeled AMB-1, positron emission tomography imaging revealed increasing colonization of tumors and decreasing infection of organs after 4 hours. Viable cell counts showed that, by day 6, the bacteria had colonized tumors but were cleared completely from other organs. Magnetic resonance imaging showed a 1.22-fold (P = 0.003) increased positive contrast in tumors on day 2 and a 1.39-fold increase (P = 0.0007) on day 6.
Conclusion: Magnetotactic bacteria can produce positive magnetic resonance imaging contrast and colonize mouse tumor xenografts, providing a potential tool for improved magnetic resonance imaging visualization in preclinical and translational studies to track cancer. (Clin Cancer Res 2009;15(16):5170–7)
Elevated Cutaneous Smad Activation Associates with Enhanced Skin Tumor Susceptibility in Organ Transplant Recipients
Authors: Harradine Kelly A. , Ridd Katie , Saunier Elise F. , Clermont Frederic F. , Perez-Losada Jesus , Moore Dan H. , Epstein Ervin H. , Bastian Boris C. , Akhurst Rosemary J. 
Published: August 2009

Abstract
Purpose: Nonmelanoma skin cancer incidence is enhanced &gt;50-fold in patients taking antirejection drugs (ARD) following organ transplantation. Preclinical studies suggest that ARD treatment increases transforming growth factor-β1 (TGF-β1) levels, which contribute to enhanced tumor susceptibility independent of the immunosuppressive effects of ARDs. This study investigates whether TGF-β signaling is elevated in transplant patients.
Experimental Design: Immunohistochemical tissue microarray analysis was used to determine the levels of TGF-β1, TGF-β2, TGF-β3, TβRII, and activated P-Smad2/3 and P-Smad1/5/8, which are phosphorylated directly by distinct TGF-β/BMP receptor complexes. We analyzed &gt;200 cutaneous lesions and adjacent nonlesional skin samples from 87 organ transplant recipients, and 184 cutaneous lesions and adjacent skin samples from 184 individuals who had never received ARDs.
Results: We found significantly higher levels of P-Smad2 in both nonlesional and lesional tissue from transplant recipients compared with those not exposed to ARDs (P ≤ 0.001). In contrast, P-Smad1/5/8, a marker of activation of the bone morphogenetic protein signaling pathway, was generally not expressed at higher levels in patients taking ARDs, including analysis of nonlesional skin, actinic keratoses, carcinoma in situ, or squamous cell carcinoma but was differentially expressed between keratoacanthoma from transplant recipients compared with those from non–transplant recipients (P ≤ 0.005).
Conclusions: Observation of elevated P-Smad2 levels in transplant recipients is consistent with the notion that elevated TGF-β signaling may contribute to malignancy in organ transplant recipients. Disparate P-Smad1/5/8 expression levels between keratoacanthoma from the two patient groups might reflect the distinct BMP-responsive cell of origin for this hair follicle–derived lesion. (Clin Cancer Res 2009;15(16):5101–7)
Reexpression of Human Somatostatin Receptor Gene 2 Gene Mediated by Oncolytic Adenovirus Increases Antitumor Activity of Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand against Pancreatic Cancer
Authors: Zhang Zhenwei , Huang Yangbin , Newman Kam , Gu Jinfa , Zhang Xuemei , Wu Hua , Zhao Ming , Xianyu Zhiqun , Liu Xinyuan 
Published: August 2009

Abstract
Purpose: Pancreatic cancer continues to pose an enormous challenge to clinicians and cancer scientists. Clinical studies show that tumor necrosis factor–related apoptosis- inducing ligand (TRAIL) exerts a potent and tumor-specific proapoptotic activity. However, most pancreatic cancer cells are resistant to TRAIL therapy. Human somatostatin receptor gene 2 (hSSTr2) is lost in 90% of pancreatic carcinoma. Oncolytic viruses are able to selectively lyse cancer cells and represent a promising novel anticancer therapy. Here, we investigated whether oncolytic adenovirus–mediated reexpression of hSSTr2 would enhance TRAIL-induced antitumor efficacy against pancreatic cancer.
Experimental Design: The antitumor efficacies of combined or single treatment of hSSTr2 and TRAIL mediated by oncolytic adenovirus were compared in pancreatic cancer cell culture and xenografts. The mechanisms involved in hSSTr2-induced sensitization to TRAIL were studied.
Results: Oncolytic adenovirus–mediated reexpression of hSSTr2 potentiated TRAIL-induced tumor growth inhibition in vitro and in vivo. Reexpression of hSSTr2 augmented TRAIL-induced apoptosis against pancreatic cancer cells via up-regulation of death receptor 4 and down-regulation of Bcl-2.
Conclusions: hSSTr2 restoration mediated by oncolytic adenovirus enhances TRAIL-induced antitumor efficacy against pancreatic cancer. Combined treatment with oncolytic adenovirus–mediated hSSTr2 and TRAIL gene provides the rationale for a clinical trial in pancreatic cancer. (Clin Cancer Res 2009;15(16):5154–60)
Phase I Trial of Continuous Infusion Anti-Mesothelin Recombinant Immunotoxin SS1P
Authors: Kreitman Robert J. , Hassan Raffit , FitzGerald David J. , Pastan Ira 
Published: August 2009

Abstract
Purpose: To conduct a phase I trial of recombinant immunotoxin SS1P given by continuous infusion in chemoresistant solid tumors expressing mesothelin.
Experimental Design: Eligible patients had mesothelioma, ovarian, or pancreatic cancer, which was recurrent or unresectable despite standard therapy, and were mesothelin positive by immunohistochemistry. SS1P was given by continuous infusion for 10 days, and cycles could be repeated at 4-week intervals in the absence of neutralizing antibodies or progressive disease.
Results: Twenty-four patients, five with peritoneal mesothelioma, nine with pleural mesothelioma, two with pleural-peritoneal mesothelioma, seven with ovarian carcinoma, and one with pancreatic carcinoma, received 4, 8, 12, 18, and 25 μg/kg/d ×10. The maximum tolerated dose was 25 μg/kg/d ×10, where one of six patients had dose-limiting toxicity due to reversible vascular leak syndrome. Immunogenicity was observed in 18 (75%) of 24 patients, and five (21%) received a second cycle. Constant plasma levels of SS1P were maintained for most of the 10-day infusion time, with median peak levels of up to 153 ng/mL. One patient had a partial response. Nonmajor responses included cessation of ascites and independence from paracentesis, resolution of masses by positron emission tomography, and improved pain and range of motion.
Conclusions: As a single agent by continuous infusion, recombinant immunotoxin SS1P was well tolerated up to 25 μg/kg/d ×10 and showed evidence of modest clinical activity. Continuous infusion showed no significant advantage over bolus dosing, and further clinical development of SS1P is proceeding by bolus dosing in combination with chemotherapy. (Clin Cancer Res 2009;15(16):5274–9)