bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting vascular endothelial growth factor receptor-1 and -3 with cediranib (AZD2171): effects on migration and invasion of gastrointestinal cancer cell lines
Authors: Morelli M. Pia , Brown Amy M. , Pitts Todd M. , Tentler John J. , Ciardiello Fortunato , Ryan Anderson , Jürgensmeier Juliane M. , Eckhardt S. Gail 
Published: September 2009

AbstractThe effect of vascular endothelial growth factor (VEGF) ligands and cediranib on tumor cell proliferation, migration, and invasion was determined. It has recently been suggested that autocrine signaling through the VEGF receptor (VEGFR) pathway may play a role in tumor cell survival, invasion, and migration. The purpose of the present study was to determine the expression of VEGFRs and VEGFR ligands in a panel of gastrointestinal carcinoma cells. Additionally, we evaluated the effects of VEGF autocrine signaling on tumor cell proliferation, migration, and invasion utilizing cediranib (AZD2171), a pan-VEGFR inhibitor. Five colorectal, three pancreatic, and two hepatocellular carcinoma cell lines were screened for VEGFR and VEGF expression by several methods. Expression of VEGFR-1 and VEGFR-3 was cell line–dependent, whereas VEGFR-2 was not detected. Secretion of VEGF-A was detected in the supernatants of all cell lines whereas VEGF-C secretion was detected in the Panc-1, MiaPaca2, and Hep1 cells only. Tumor cells showed increased migratory activity, but not proliferation, when stimulated with VEGFs. The pan-VEGFR inhibitor cediranib (100 nmol/L) inhibited tumor cell migration and invasion, with no effects on proliferation. Cediranib decreased VEGFR-1 and VEGFR-3 phosphorylation as well as activation of downstream effectors. VEGFR-1 and VEGFR-3 expression was detected in all the gastrointestinal carcinoma cells evaluated. Although activation of the VEGF pathway did not affect cell proliferation, our data indicate that this pathway seems to play a role in tumor cell migration and invasion in these cell lines. Therefore, inhibition of VEGFR by cediranib may represent a clinically relevant treatment option for gastrointestinal tumors. [Mol Cancer Ther 2009;8(9):2546–58]
The use of a mini bypass circuit for minimally invasive mitral valve surgery
Authors: Fernandes P. , MacDonald J. , Cleland A. , Mayer R. , Fox S. , Kiaii B. 
Published: September 2009

Introduction: The purpose of the study is to clinically evaluate minimally invasive mitral valve surgeries (MIMVS) using a mini bypass circuit. The challenge to perfusion is to keep pace with MIMVS, with demonstrated improvements in perfusion-related technologies. Methods: From October 28, 2005 to September 10, 2008, we retrospectively evaluated thirty-four elective cases which used the mini-circuit (Medtronic Resting Heart System®), with respect to safety, efficacy, cannulation technique, blood usage, resultant hemoglobin, length of ICU and hospital stay, and complications. Conclusion: The Medtronic Resting Heart System® alleviates many factors, such as high shear stress, turbulence, air to blood interface and decreased oncotic pressure caused by hemodilution, providing more efficient perfusion to our MIMVS patients. We demonstrate, with minor circuit modifications and attention to venous air issues, that this mini-circuit can be used safely and effectively, while being associated with improvements in patient outcomes.
Preoperative screening and management of carotid artery disease in patients undergoing cardiac surgery
Authors: Anastasiadis Kyriakos , Karamitsos Theodoros D. , Velissaris Ioannis , Makrygiannakis Konstantinos , Kiskinis Dimitrios 
Published: September 2009

Background: Carotid artery stenosis (CAS) is a well-known risk factor for perioperative stroke in cardiac surgery. It is unclear whether preoperative carotid screening should be applied to all patients. Carotid intervention concomitantly with cardiac operations is also controversial. Our objective was to identify the prevalence of significant CAS and its related risk factors by applying a protocol of preoperative carotid screening to all patients undergoing cardiac surgery. Methods: We studied 307 patients who were primarily screened preoperatively by duplex Doppler ultrasonography. Catheter carotid angiography or transcranial Doppler was performed on equivocal cases. Univariate and multivariate analyses were applied across selected parameters to identify risk factors for significant CAS (> 70%). The prevalence of CAS and perioperative stroke rates were determined. Results: Twenty-two patients with severe and 18 with moderate carotid stenosis were identified. Further radiological evaluation with catheter carotid angiography and transcranial Doppler confirmed the presence of significant CAS in 20 patients who underwent carotid stenting or endarterectomy before the open heart surgery. The cardiac surgeon was free to modify the surgical technique according to the preoperative assessment. No patient had major stroke perioperatively, while two minor strokes with complete neurologic recovery have been documented. The history of stroke and the presence of bruit on clinical examination were the only significant predictors of severe carotid disease. Conclusion: Careful clinical examination together with detailed previous history taking can identify the majority of patients with CAS. Further data are required for the construction of a scientifically valid policy as a guideline.
Gap Formation in Transpatellar Patellar Tendon Repair
Authors: Krushinski Erik M. , Parks Brent G. , Hinton Richard Y. 
Published: September 2009

Background Postfixation loosening within the Krackow stitch–tendon construct may be associated with gap formation in patellar tendon repair. Hypothesis Pretensioning the Krackow stitch–tendon construct decreases postfixation gap formation in transpatellar patellar tendon repair. Study Design Controlled laboratory study. Methods Patellar tendon rupture was simulated in 8 pairs of cadaveric knees. Standard manual traction was used in all specimens to remove Krackow stitch slack. In the experimental group, specimens were pretensioned with a simulated active concentric quadriceps contraction with cycling of the knee 10 times from 90° to 5° of flexion. All specimens were then cycled at 0.25 Hz from 90° to 5° for 1000 cycles until failure, which was defined as 3 or 5 mm of gap formation. Results A 3-mm gap occurred at 1 cycle (mean, 3.5 mm) and 35 cycles (4.0 mm) in the control and experimental groups, respectively. Gapping of 5 mm occurred at 35 (5.9 mm) and 100 cycles (5.0 mm) in the control and experimental specimens, respectively. Gap formation was smaller in the experimental group through 100 cycles (P < .05). Conclusion Gapping was lower with pretensioning in the early cycling stages. However, significant gapping occurred in both groups with repetitive concentric active loading ranging from 90° to 5° of flexion. Clinical Relevance Tightening of the Krackow stitch as done in this study does not result in a clinically important decrease in gapping. This observation may be generalizable to other applications of the Krackow stitch.
Defects in osteoblast function but no changes in long-term repopulating potential of hematopoietic stem cells in a mouse chronic inflammatory arthritis model
Authors: Ma Yunglin D. , Park Changwon , Zhao Haibo , Oduro Kwadwo A. , Tu Xiaolin , Long Fanxin , Allen Paul M. , Teitelbaum Steven L. , Choi Kyunghee 
Published: September 2009

Abstract
Recent studies support the notion that there is an intricate relationship between hematopoiesis and bone homeostasis in normal steady states. Using mice undergoing chronic inflammatory arthritis, we investigated the relationship between hematopoiesis and bone homeostasis in pathologic conditions. We demonstrate that mice undergoing chronic inflammatory arthritis displayed osteoporosis resulting from a severe defect in osteoblast function. Despite the defective osteoblast function, however, the hematopoietic stem cells from these mice exhibited normal properties in either long-term repopulation or cell cycling. Therefore, the bone-forming capacity of osteoblasts is distinct from their ability to maintain hematopoietic stem cells in chronic inflammatory conditions.
In Silico screening for functional candidates amongst hypothetical proteins
Authors: Desler Claus , Suravajhala Prashanth , Sanderhoff May , Rasmussen Merete , Rasmussen Lene Juel 
Published: September 2009

Abstract

Background
The definition of a hypothetical protein is a protein that is predicted to be expressed from an open reading frame, but for which there is no experimental evidence of translation. Hypothetical proteins constitute a substantial fraction of proteomes of human as well as of other eukaryotes. With the general belief that the majority of hypothetical proteins are the product of pseudogenes, it is essential to have a tool with the ability of pinpointing the minority of hypothetical proteins with a high probability of being expressed.

Results
Here, we present an in silico selection strategy where eukaryotic hypothetical proteins are sorted according to two criteria that can be reliably identified in silico: the presence of subcellular targeting signals and presence of characterized protein domains. To validate the selection strategy we applied it on a database of human hypothetical proteins dating to 2006 and compared the proteins predicted to be expressed by our selecting strategy, with their status in 2008. For the comparison we focused on mitochondrial proteins, since considerable amounts of research have focused on this field in between 2006 and 2008. Therefore, many proteins, defined as hypothetical in 2006, have later been characterized as mitochondrial.

Conclusion
Among the total amount of human proteins hypothetical in 2006, 21% have later been experimentally characterized and 6% of those have been shown to have a role in a mitochondrial context. In contrast, among the selected hypothetical proteins from the 2006 dataset, predicted by our strategy to have a mitochondrial role, 53-62% have later been experimentally characterized, and 85% of these have actually been assigned a role in mitochondria by 2008.
Therefore our in silico selection strategy can be used to select the most promising candidates for subsequent in vitro and in vivo analyses.
Protective effect of geranylgeranylacetone, an inducer of heat shock protein 70, against drug-induced lung injury/fibrosis in an animal model
Authors: Fujibayashi Takayoshi , Hashimoto Naozumi , Jijiwa Mayumi , Hasegawa Yoshinori , Kojima Toshihisa , Ishiguro Naoki 
Published: September 2009

Abstract

Background
To determine whether oral administration of geranylgeranylacetone (GGA), a nontoxic anti-ulcer drug that is an inducer of heat shock protein (HSP) 70, protects against drug-induced lung injury/fibrosis in vivo.

Methods
We used a bleomycin (BLM)-induced lung fibrosis model in which mice were treated with oral 600 mg/kg of GGA before and after BLM administration. Inflammation and fibrosis were evaluated by histological scoring, hydroxyproline content in the lung and inflammatory cell count, and quantification by ELISA of macrophage inflammatory protein-2 (MIP-2) in bronchoalveolar lavage fluid. Apoptosis was evaluated by the TUNEL method. The induction of HSP70 in the lung was examined with western blot analysis and its localization was determined by immunohistochemistry.

Results
We confirmed the presence of inflammation and fibrosis in the BLM-induced lung injury model and induction of HSP70 by oral administration of GGA. GGA prevented apoptosis of cellular constituents of lung tissue, such as epithelial cells, most likely related to the de novo induction of HSP70 in the lungs. GGA-treated mice also showed less fibrosis of the lungs, associated with the findings of suppression of both production of MIP-2 and inflammatory cell accumulation in the injured lung, compared with vehicle-treated mice.

Conclusion
GGA had a protective effect on drug-induced lung injury/fibrosis. Disease-modifying antirheumatic drugs such as methotrexate, which are indispensable for the treatment of rheumatoid arthritis, often cause interstitial lung diseases, an adverse event that currently cannot be prevented. Clinical use of GGA for drug-induced pulmonary fibrosis might be considered in the future.
Monodispersity of recombinant Cre recombinase correlates with its effectiveness in vivo
Authors: Capasso Paola , Aliprandi Marisa , Ossolengo Giuseppe , Edenhofer Frank , de Marco Ario 
Published: September 2009

AbstractBackgroundCre recombinase is a common reagent used for thein vivoon/off switching of the expression of target genes flanked byloxPsites. In particular, recombinant TAT-Cre fusion constructs purified from bacteria have been used to promote the cell uptake of the enzyme. However, the recovery of active TAT-Cre remains a demanding process and its specific activity varies significantly among batches, making difficult data comparison.ResultsWe noticed a strong correlation between recombinase activity and enzyme monodispersity. The existence of such correlation enabled us to indirectly monitor the TAT-Cre recombinase activity during the multi-step purification process by measuring its monodispersity, a parameter detectable by means of a spectrofluorimetric assay that allows the calculation of the Aggregation Index (AI) in an easy and rapid way. AI values were recorded after each purification passage to identify the critical steps and to choose optimal alternatives for chromatographic conditions, desalting procedures, and protocols for bacterial endotoxin removal. Furthermore, the effect of metal ions and temperature on TAT-Cre aggregation and inactivation was characterizedin vitro. Finally, we optimized the enzyme delivery protocolin vivoby following the accumulation tuning of the reporter protein β-catenin.ConclusionA rational purification protocol for TAT-Cre has been developed by choosing the options that minimize the enzyme aggregation. Our data suggest that AI measurement should support the optimization of any protocol aiming at the recovery of monodispersed protein.
Human cellular restriction factors that target HIV-1 replication
Authors: Strebel Klaus , Luban Jeremy , Jeang Kuan-Teh 
Published: September 2009

Abstract
Recent findings have highlighted roles played by innate cellular factors in restricting intracellular viral replication. In this review, we discuss in brief the activities of apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G), bone marrow stromal cell antigen 2 (BST-2), cyclophilin A, tripartite motif protein 5 alpha (Trim5α), and cellular microRNAs as examples of host restriction factors that target HIV-1. We point to countermeasures encoded by HIV-1 for moderating the potency of these cellular restriction functions.
Nested-multiplex PCR detection of Orthopoxvirus and Parapoxvirus directly from exanthematic clinical samples
Authors: Abrahão Jônatas S , Lima Larissa S , Assis Felipe L , Alves Pedro A , Silva-Fernandes André T , Cota Marcela MG , Ferreira Vanessa M , Campos Rafael K , Mazur Carlos , Lobato Zélia IP , Trindade Giliane S , Kroon Erna G 
Published: September 2009

AbstractBackgroundOrthopoxvirus(OPV) andParapoxvirus(PPV) have been associated with worldwide exanthematic outbreaks. Some species of these genera are able to infect humans and domestic animals, causing serious economic losses and public health impact. Rapid, useful and highly specific methods are required to detect and epidemiologically monitor such poxviruses. In the present paper, we describe the development of a nested-multiplex PCR method for the simultaneous detection of OPV and PPV species directly from exanthematic lesions, with no previous viral isolation or DNA extraction.Methods and ResultsThe OPV/PPV nested-multiplex PCR was developed based on the evaluation and combination of published primer sets, and was applied to the detection of the target pathogens. The method showed high sensitivity, and the specificity was confirmed by amplicon sequencing. Exanthematic lesion samples collected during bovine vaccinia or contagious ecthyma outbreaks were submitted to OPV/PPV nested-multiplex PCR and confirmed its applicability.ConclusionThese results suggest that the presented multiplex PCR provides a highly robust and sensitive method to detect OPV and PPV directly from clinical samples. The method can be used for viral identification and monitoring, especially in areas where OPV and PPV co-circulate.
Identification of biology-based breast cancer types with distinct predictive and prognostic features: role of steroid hormone and HER2 receptor expression in patients treated with neoadjuvant anthracycline/taxane-based chemotherapy
Authors: Darb-Esfahani Silvia , Loibl Sibylle , Müller Berit M , Roller Marc , Denkert Carsten , Komor Martina , Schlüns Karsten , Blohmer Jens Uwe , Budczies Jan , Gerber Bernd , Noske Aurelia , du Bois Andreas , Weichert Wilko , Jackisch Christian , Dietel Manfred , Richter Klaus , Kaufmann Manfred , von Minckwitz Gunter 
Published: September 2009

Abstract
Introduction
Reliable predictive and prognostic markers for routine diagnostic purposes are needed for breast cancer patients treated with neoadjuvant chemotherapy. We evaluated protein biomarkers in a cohort of 116 participants of the GeparDuo study on anthracycline/taxane-based neoadjuvant chemotherapy for operable breast cancer to test for associations with pathological complete response (pCR) and disease-free survival (DFS). Particularly, we evaluated if interactions between hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) expression might lead to a different clinical behavior of HR+/HER2+ co-expressing and HR+/HER2- tumors and whether subgroups of triple negative tumors might be identified by the help of Ki67 labeling index, cytokeratin 5/6 (CK5/6), as well as cyclooxygenase-2 (COX-2), and Y-box binding protein 1 (YB-1) expression.

Methods
Expression analysis was performed using immunohistochemistry and silver-enhanced in situ hybridization on tissue microarrays (TMAs) of pretherapeutic core biopsies.

Results
pCR rates were significantly different between the biology-based tumor types (P = 0.044) with HR+/HER2+ and HR-/HER2- tumors having higher pCR rates than HR+/HER2- tumors. Ki67 labeling index, confirmed as significant predictor of pCR in the whole cohort (P = 0.001), identified HR-/HER- (triple negative) carcinomas with a higher chance for a pCR (P = 0.006). Biology-based tumor type (P = 0.046 for HR+/HER2+ vs. HR+/HER2-), Ki67 labeling index (P = 0.028), and treatment arm (P = 0.036) were independent predictors of pCR in a multivariate model. DFS was different in the biology-based tumor types (P < 0.0001) with HR+/HER2- and HR+/HER2+ tumors having the best prognosis and HR-/HER2+ tumors showing the worst outcome. Biology-based tumor type was an independent prognostic factor for DFS in multivariate analysis (P < 0.001).

Conclusions
Our data demonstrate that a biology-based breast cancer classification using estrogen receptor (ER), progesterone receptor (PgR), and HER2 bears independent predictive and prognostic potential. The HR+/HER2+ co-expressing carcinomas emerged as a group of tumors with a good response rate to neoadjuvant chemotherapy and a favorable prognosis. HR+/HER2- tumors had a good prognosis irrespective of a pCR, whereas patients with HR-/HER- and HR-/HER+ tumors, especially if they had not achieved a pCR, had an unfavorable prognosis and are in need of additional treatment options.

Trial registration
ClinicalTrials.gov identifier: NCT00793377
Successful Use of Dexmedetomidine for Sedation in a 24-Week Gestational Age Neonate
Authors: O'Mara Keliana , Gal Peter , Ransom J Laurence , Jr John E Wimmer , Carlos Rita Q , Dimaguila Mary Ann VT , Davonzo Christie , Smith McCrae 
Published: September 2009

Objective: To describe a case of dexmedetomidine use for sedation in a 24-week gestational age premature neonate. Case Summary: A 9-day-old, 24-week gestational age male neonate on high-frequency oscillatory mechanical ventilation was experiencing severe agitation refractory to high-dose intravenous narcotics and benzodiazepines. Since the infant's respiratory stability was reliant on adequate sedation, he was given dexmedetomidine after several days of suboptimal response to escalation of standard agents. Treatment prior to dexmedetomidine included continuous-infusion fentanyl 10 μg/kg/h, intravenous lorazepam 0.6 mg/kg every 4 hours, intermittent doses of both lorazepam and midazolam as needed, and a single bolus dose of phenobarbital. The patient calmed markedly during the dexmedetomidine loading dose infusion and remained adequately sedated while the drug was continued. The dexmedetomidine infusion allowed weaning of mechanical ventilation settings and eventual extubation of the infant, as well as rapid tapering of other sedative medications. The maximum dexmedetomidine infusion rate was 0.7 μg/kg/h, and total duration of therapy was 19 days. No significant adverse effects were directly attributed to dexmedetomidine use during this time. Discussion: Dexmedetomidine is a novel α2-agonist approved for short-term sedation in mechanically ventilated adults. Data describing its use in pediatric and neonatal patients continue to emerge. The prolonged use of dexmedetomidine in very-low-birth-weight neonates has not been described in the literature. Conclusions: Dexmedetomidine was an effective sedative and analgesic in a 24-week gestational age neonate treated for refractory agitation while on mechanical ventilation. Based on its documented efficacy for pain and sedation and its favorable adverse effect profile, dexmedetomidine warrants further study as first-line or adjunct therapy with narcotics for sedation in ventilated newborns.
Quantitative Assessment of Irradiation Effect on Creep and Corrosion Properties of Zr-Base Alloys
Authors: Kido T , Senda Y , Tukuta Y , Hayashi H , Murai K 
Published: September 2009

In order to qualify the properties of alternative zirconium-base alloys as fuel cladding material in PWRs, the segmented fuel rod irradiation program is being performed. In this program, segmented fuel rods were irradiated in Vandellos-2 to have burn-ups of 25 to 60 GWd/t, and more than 40 rods were examined by profilometry and/or eddy-current oxide measurement in hot cells at Studsvik. In parallel to the irradiation test, out-of-pile creep and corrosion tests were carried out on the archive claddings.
One segmented fuel rod consists of seven segments axially connected, and it therefore has a unique feature, existence of plenums in the middle of the fuel stack region (in-flux plenum). Since evaluation of the temperature at plenums during operation is easier than at fuel regions, direct comparisons of the creep and corrosion behaviors with and without irradiation were able to be done.
The irradiation effect on the corrosion properties were determined to accelerate the corrosion rate by a factor of 2 to 3 as increasing exposure time in the reactor irrespective of the cladding variants. On the other hand, evaluations of the creep-down behavior at plenums have shown that niobium-bearing zirconium alloys (MDA: 0.8Sn-0.2Fe-0.1Cr-0.5Nb, ZIRLO™: 1Sn-0.1Fe-1Nb) had an irradiation creep rate of 1/2 to 2/3 compared to that of Zircaloy-4, whereas conventional tin and low tin Zircaloy-4s showed little difference. This restraining effect of niobium is comparable to the influence of niobium on the axial length change of the rods.