bluuebunny/crossref_metadata_2025_split huggingface dataset:
CXCR4-Targeted Therapy Inhibits VEGF Expression and Chondrosarcoma Angiogenesis and Metastasis
Authors: Sun Xiaojuan , Charbonneau Cherie , Wei Lei , Yang Wentian , Chen Qian , Terek Richard M. 
Published: May 2013

AbstractChondrosarcoma is notable for its lack of response to conventional cytotoxic chemotherapy, propensity for developing lung metastases, and poor survival. Therefore, a better understanding of angiogenic and metastatic pathways is needed. Multiple pathways regulate angiogenesis and metastasis, including chemokines and their receptors. In this study, we investigated chemokine (C-X-C motif) receptor 4 (CXCR4) signaling in chondrosarcoma and tested the hypotheses that CXCR4 inhibition suppresses tumor angiogenesis and metastasis. CXCR4 expression, analyzed by real-time PCR and Western blot, was increased in human chondrosarcoma cell line JJ compared with normal chondrocytes and was further increased in JJ by hypoxia (2% O2), vascular endothelial growth factor A (VEGFA; 10 ng/mL), and in xenograft tumors in nude mice. The CXCR4 ligand CXCL12 (10 ng/mL) doubled secreted VEGFA, measured with ELISA, under hypoxic conditions and this conditioned media increased human umbilical vein endothelial cell tube formation. These effects were inhibited by CXCR4 siRNA or AMD3100 (5 μg/mL). In a xenograft mouse model, four weeks of AMD3100 treatment (1.25 mg/kg, intraperitoneally twice daily) inhibited tumor angiogenesis, tumor growth, and metastasis. VEGFA content in tumor extracts was decreased (7.19 ± 0.52 ng/mL control vs. 3.96 ± 0.66 treatment) and bioimaging of angiogenesis was decreased by 56%. Tumor volumes averaged 4.44 ± 0.68 cm3 in control compared with 2.48 ± 0.61 cm3 in the treatment group. The number of lung metastatic nodules was 23 ± 9 in control compared with 10 ± 6 in the treatment group (N = 8/group). Therefore, CXCR4-targeted therapy may be a treatment strategy for chondrosarcoma. Mol Cancer Ther; 12(7); 1163–70. ©2013 AACR.
Polo-like Kinase Inhibitor Ro5203280 Has Potent Antitumor Activity in Nasopharyngeal Carcinoma
Authors: Cheung Arthur Kwok Leung , Yan Ip Joseph Chok , Lung Hong Lok , Wu Jim Zhen , Tsao Sai Wah , Lung Maria Li 
Published: May 2013

AbstractNasopharyngeal carcinoma is a cancer with its highest prevalence among the southern Chinese and is rare elsewhere in the world. The main treatment modalities include chemotherapy and radiotherapy. However, tumor chemoresistance often limits the efficacy of nasopharyngeal carcinoma treatment and reduces survival rates. Thus, identifying new selective chemotherapeutic drugs for nasopharyngeal carcinoma treatment is needed. In this current study, the antitumor efficacy of a polo-like kinase inhibitor, Ro5203280, was investigated. Ro5203280 induces tumor suppression both in vitro and in vivo. An inhibitory effect was observed with the highly proliferating cancer cell lines tested, but not with the nontumorigenic cell line. Real-time cell proliferation and fluorescence-activated cell sorting (FACS) analysis, together with immunohistochemical (IHC), immunofluorescence, and Annexin V staining assays, were used to evaluate the impact of drug treatment on cell cycle and apoptosis. Ro5203280 induces G2–M cell-cycle arrest and apoptosis. Western blotting shows it inhibits PLK1 phosphorylation and downregulates the downstream signaling molecule, Cdc25c, and upregulates two important mitosis regulators, Wee1 and Securin, as well as the DNA damage-related factor Chk2 in vitro and in vivo. In vivo tumorigenicity assays with Ro5203280 intravenous injection showed its potent ability to inhibit tumor growth in mice, with no observable signs of toxicity. These findings suggest the potential usefulness of Ro5203280 as a chemotherapeutic targeting drug for nasopharyngeal carcinoma treatment. Mol Cancer Ther; 12(8); 1393–401. ©2013 AACR.
Stromal EGF and IGF-I Together Modulate Plasticity of Disseminated Triple-Negative Breast Tumors
Authors: Castaño Zafira , Marsh Timothy , Tadipatri Ramya , Kuznetsov Hanna S. , Al-Shahrour Fatima , Paktinat Mahnaz , Greene-Colozzi April , Nilsson Björn , Richardson Andrea L. , McAllister Sandra S. 
Published: May 2013

Abstract
The causes for malignant progression of disseminated tumors and the reasons recurrence rates differ in women with different breast cancer subtypes are unknown. Here, we report novel mechanisms of tumor plasticity that are mandated by microenvironmental factors and show that recurrence rates are not strictly due to cell-intrinsic properties. Specifically, outgrowth of the same population of incipient tumors is accelerated in mice with triple-negative breast cancer (TNBC) relative to those with luminal breast cancer. Systemic signals provided by overt TNBCs cause the formation of a tumor-supportive microenvironment enriched for EGF and insulin-like growth factor-I (IGF-I) at distant indolent tumor sites. Bioavailability of EGF and IGF-I enhances the expression of transcription factors associated with pluripotency, proliferation, and epithelial–mesenchymal transition. Combinatorial therapy with EGF receptor and IGF-I receptor inhibitors prevents malignant progression. These results suggest that plasticity and recurrence rates can be dictated by host systemic factors and offer novel therapeutic potential for patients with TNBC.
Significance: Currently, processes that mediate progression of otherwise indolent tumors are not well understood, making it difficult to accurately predict which patients with cancer are likely to relapse. Our findings reveal novel mechanisms of tumor phenotypic and gene expression plasticity that are mandated by microenvironmental factors, identifying novel therapeutic targets for patients with TNBC. Cancer Discov; 3(8); 922–35. ©2013 AACR.
This article is highlighted in the In This Issue feature, p. 826
Three-Dimensional Architecture of Scar and Conducting Channels Based on High Resolution ce-CMR
Authors: Fernández-Armenta Juan , Berruezo Antonio , Andreu David , Camara Oscar , Silva Etelvino , Serra Luis , Barbarito Valeria , Carotenutto Luigi , Evertz Reinder , Ortiz-Pérez José T. , De Caralt Teresa María , Perea Rosario Jesús , Sitges Marta , Mont Lluis , Frangi Alejandro , Brugada Josep 
Published: May 2013

Background—
Conducting channels are the target for ventricular tachycardia (VT) ablation. Conducting channels could be identified with contrast enhanced–cardiac magnetic resonance (ce-CMR) as border zone (BZ) corridors. A 3-dimensional (3D) reconstruction of the ce-CMR could allow visualization of the 3D structure of these BZ channels.

Methods and Results—

We included 21 patients with healed myocardial infarction and VT. A 3D high-resolution 3T ce-CMR was performed before CARTO-guided VT ablation. The left ventricular wall was segmented and characterized using a pixel signal intensity algorithm at 5 layers (endocardium, 25%, 50%, 75%, epicardium). A 3D color-coded shell map was obtained for each layer to depict the scar core and BZ distribution. The presence/characteristics of BZ channels were registered for each layer. Scar area decreased progressively from endocardium to epicardium (scar area/left ventricular area: 34.0±17.4% at endocardium, 24.1±14.7% at 25%, 16.3±12.1% at 50%, 13.1±10.4 at 75%, 12.1±9.3% at epicardium;
P
<0.01). Forty-five BZ channels (2.1±1.0 per patient, 23.7±12.0 mm length, mean minimum width 2.5±1.5 mm) were identified, 85% between the endocardium and 50% shell and 76% present in ≥1 layer. The ce-CMR–defined BZ channels identified 74% of the critical isthmus of clinical VTs and 50% of all the conducting channels identified in electroanatomic maps.

Conclusions—
Scar area in patients with healed myocardial infarction decreases from the endocardium to the epicardium. BZ channels, more commonly seen in the endocardium, display a 3D structure within the myocardial wall that can be depicted with ce-CMR. The use of ce-CMR–derived maps to guide VT ablation warrants further investigation.
Clinical Impact of Adenosine Triphosphate Injection on Arrhythmogenic Superior Vena Cava in the Context of Atrial Fibrillation Ablation
Authors: Miyazaki Shinsuke , Taniguchi Hiroshi , Komatsu Yuki , Uchiyama Takashi , Kusa Shigeki , Nakamura Hiroaki , Hachiya Hitoshi , Hirao Kenzo , Iesaka Yoshito 
Published: May 2013

Background—
Superior vena cava (SVC) is an infrequent yet an important source of atrial fibrillation. The clinical impact of ATP injection on arrhythmogenic SVC has not been evaluated.

Methods and Results—
A total of 43 patients (59±11 years; men, 32) who underwent ATP test for arrhythmogenic SVC after the electric isolation at either initial procedure or repeat procedure were included. Pulmonary vein antrum isolation was performed at index procedure in all patients. SVC was isolated after identifying the arrhythmogenicity at index and repeat atrial fibrillation ablation procedure in 34 (79.1%) and 9 (20.9%) patients, respectively. Atrial fibrillation originated from the SVC spontaneously and under isoproterenol infusion in 30 (75.0%) patients, and immediately after ATP injection in 10 (25.0%) patients. Tachycardia persistently confined to SVC was recorded after electric isolation in 13 (30.2%) patients. SVC reconnection was provoked by ATP test in 7 of 36 (19.4%) patients at acute phase. At median 4.0 (2.25–7.5) months after SVC isolation, reconnection was observed in 12 of 15 (80.0%) patients at repeat procedure. Among 12 patients with reconnection at baseline, SVC reconnection was provoked by ATP test after reisolation in 1 (8.3%) patient. Among 3 patients without SVC reconnection at baseline, reconnection was provoked by ATP test at chronic phase in 1 patient.

Conclusions—
Dormant conduction between an arrhythmogenic SVC and the right atrium can be exposed by ATP administration both immediately and late after isolation, potentially facilitating detection and ablation for isolation.
Impact of International Normalized Ratio and Activated Clotting Time on Unfractionated Heparin Dosing During Ablation of Atrial Fibrillation
Authors: Hamam Ismail , Daoud Emile G. , Zhang Jianying , Kalbfleisch Steven J. , Augostini Ralph , Winner Marshall , Tsai Shane , Rhodes Troy E. , Houmsse Mahmoud , Liu Zhenguo , Love Charles J. , Tyler Jaret , Sachdev Molly , Weiss Raul , Hummel John D. 
Published: May 2013

Background—
For ablation of atrial fibrillation, it is unclear how baseline international normalized ratio (INR) affects the dosing of unfractionated heparin (UFH).

Methods and Results—

A retrospective review of 170 consecutive patients undergoing atrial fibrillation ablation with baseline activated clotting time (ACT) and INR values was performed. Patients were grouped according to INR <2.0 (G<2; n=129) and INR ≥2.0 (G≥2; n=41). Clinical variables, UFH doses, and ACT values were recorded. An equation was derived to calculate the first bolus of UFH required to achieve an ACT ≥300 seconds, and this was subsequently assessed in 168 patients. For the initial 170 patients, the baseline INR (2.47±0.31 versus 1.53±0.31) and ACT (185±26 versus 153±30 seconds) were significantly greater in G≥2 (
P
<0.001). The amount of UFH to achieve the first ACT ≥300 seconds was significantly higher for G<2 versus G≥2 (9701±2390 versus 8268±2366 U;
P
=0.0001). Baseline INR, ACT, and weight were predictors of the UFH dosage to achieve an ACT ≥300 seconds. An equation derived to achieve an ACT ≥300 seconds after a single bolus of UFH met this end point in 160 of 168 patients (95%).

Conclusions—
Baseline INR and ACT, in addition to weight, are the only predictors of UFH dosage needed to achieve an ACT ≥300 seconds. A derived equation predicted the UFH dosage to achieve an ACT ≥300 seconds.
Sex Differences in the Effectiveness of Early Coronary Computed Tomographic Angiography Compared With Standard Emergency Department Evaluation for Acute Chest Pain
Authors: Truong Quynh A. , Hayden Douglas , Woodard Pamela K. , Kirby Ruth , Chou Eric T. , Nagurney John T. , Wiviott Stephen D. , Fleg Jerome L. , Schoenfeld David A. , Udelson James E. , Hoffmann Udo 
Published: May 2013

Background—
We evaluate sex-based differences in the effectiveness of early cardiac computed tomographic angiography (CCTA) and standard emergency department (ED) evaluation in patients with acute chest pain.

Methods and Results—

In the Rule-Out Myocardial Infarction With Computer-Assisted Tomography (ROMICAT)-II multicenter, controlled trial, we randomized 1000 patients (47% women) 40 to 74 years of age with symptoms suggestive of acute coronary syndrome to an early CCTA or standard ED evaluation. In this prespecified analysis, women in the CCTA arm had a greater reduction in length of stay, lower hospital admission rates, and lesser increased cumulative radiation dose than men in a comparison of ED strategies (
P
for interaction ≤0.02). Although women had lower acute coronary syndrome rates than men (3% versus 12%;
P
<0.0001), sex differences in length of stay persisted after adjustment for baseline differences, including acute coronary syndrome rate (
P
for interaction <0.03). Length of stay was similar between sexes with normal CCTA findings (
P
=0.11). There was no missed acute coronary syndrome for either sex. No difference was observed in major adverse cardiac events between sexes and ED strategies (
P
for interaction =0.39). Women had more normal CCTA examinations than men (58% versus 37%;
P
<0.0001), less obstructive coronary disease by CCTA (5% versus 17%;
P
=0.0001), but similar normalcy rates for functional testing (
P
=0.65). Men in the CCTA arm had the highest rate of invasive coronary angiography (18%), whereas women had comparable low 5% rates regardless of ED strategy.

Conclusions—
This trial provides data supporting an early CCTA strategy as an attractive option in women presenting to the ED with symptoms suggestive of acute coronary syndrome. The findings may be explained by lower CAD prevalence and severity in women than men.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01084239.
Physical activity, body mass index, alcohol consumption and cigarette smoking among East Asian college students
Authors: Seo Dong-Chul , Torabi Mohammad R , Chin Ming-Kai , Lee Chung Gun , Kim Nayoung , Huang Sen-Fang , Chen Chee Keong , Mok Magdalena Mo Ching , Wong Patricia , Chia Michael , Park Bock-Hee 
Published: May 2013

Objective: To identify levels of moderate-intensity physical activity (MPA) and vigorous-intensity physical activity (VPA) in a representative sample of college students in six East Asian economies and examine their relationship with weight, alcohol consumption and cigarette smoking. Design: Cross-sectional survey. Setting: College students recruited from 21 different colleges in six East Asian economies. Method: Self-reported physical activity, weight, height, alcohol consumption, and smoking were assessed using already-validated instruments. Multiple logistic regression models of MPA and VPA were separately performed for each economy, controlling for age, gender, living area before college, military experience, paid employment, and religion. All the analyses were performed using SAS 9.2 with clustering effects accounted for. Results: Being a heavy drinker increased the odds of engaging in VPA in five economies (adjusted odds ratio [AOR] = 1.56 to 2.65). Cigarette smoking was not associated with MPA in any economy and was only associated with VPA in China (AOR = 1.54) and Taiwan (AOR = 1.48), indicating that smokers are more likely to engage in VPA than non-smokers. Conclusions: The relationship between college students’ VPA and alcohol consumption and between MPA and cigarette smoking is similar across the East Asian economies, whereas the relationship between VPA and smoking varies substantially.
The Spatial Distribution and Social Context of Homicide in Toronto’s Neighborhoods
Authors: Thompson Sara K. , Gartner Rosemary 
Published: May 2013

Objectives: To examine the social ecology of homicide in Toronto, Canada. Method: Using both ordinary least squares regression and negative binomial models, we analyze the structural correlates of 965 homicides occurring in 140 neighborhoods in Toronto between 1988 and 2003. Results: Similar to research in U.S. cities, Toronto neighborhoods with higher levels of economic disadvantage, higher proportions of young and Black residents, and greater residential instability have higher homicide rates. In contrast to U.S. studies, Toronto neighborhoods with higher proportions of residents who are recent immigrants also have higher homicide rates. In multivariate models, only two of these characteristics—economic disadvantage and the proportion of residents aged 15 to 24—are significantly associated with homicide in Toronto’s neighborhoods. Despite low levels of both lethal violence and spatial inequality in Toronto, the correlates of homicide in its neighborhoods are similar in some respects to those in U.S. cities. Conclusion: Our findings lend support to the notion of invariance in some ecological covariates of homicide but also highlight the need to be cautious about generalizing from U.S.-based research on the relationship between immigration and homicide.
Morphological and Histological Changes of Rabbit Vocal Fold after Steroid Injection
Authors: Jin Hee‐Jin , Lee Sang‐Hyuk , Lee Seon‐Uk , Lee Hyun‐Sub , Jin Sung‐Min , Kim Dong‐Hun , Chae Seung‐Wan , Sohn Jin‐Hee 
Published: May 2013

Objectives/HypothesisThe purpose of this study was to investigate the morphological and histological change of vocal folds (VFs) after steroid injection in a rabbit model.Study DesignProspective animal study.SettingTertiary academic medical center.Subjects and MethodsTwenty‐four New Zealand white rabbits were used in this study. We randomly classified rabbits into the 3 groups and triamcinolone acetonide suspension was injected to the right VF with different concentrations. Left VF was injected with the same volume of phosphate‐buffered saline as control. Endoscopic evaluation was performed to measure morphological changes. The larynges were collected for histological analysis, and the VFs were stained with hematoxylin‐eosin for assessing inflammatory response, glandular atrophy, and muscular atrophy and with Masson's trichrome for assessing collagen deposition.ResultsIn morphological assessment, there were no differences in VF mass reduction, mucosal atrophy, and granulation formation between both VFs. Histological assessments showed no significant difference in inflammatory response, glandular atrophy, and collagen deposition between both VFs. However, there was a difference in muscular atrophy and epithelial layer thinning in steroid injected right VFs. Muscular atrophy had been completely recovered over time, but mild epithelial thinning was continued until 12 weeks. The longer exposure time and larger dose did not increase the intensity of muscular atrophy or epithelial thinning.ConclusionWe demonstrated that the VF steroid injection resulted in no significant changes in morphology and histology of rabbit VF. However, steroid injection may induce several VF histological changes and these results are needed to be considered when treating humans.
Expression of the NOB1 gene and its clinical significance in papillary thyroid carcinoma
Authors: Lin Shan , Meng Wei , Zhang Wei , Liu Jia , Wang Peisong , Xue Shuai , Chen Guang 
Published: May 2013

Objective The aim of this study was to explore the relationships between expression of the NIN1/RPN12 binding protein 1 homologue gene ( NOB1) in papillary thyroid carcinoma tissue and clinicopathological variables. Methods Expression of NOB1 in papillary thyroid carcinoma, normal thyroid and benign thyroid tumour tissue was evaluated at the mRNA and protein levels by real-time fluorescence quantitative reverse transcription–polymerase chain reaction and immunohistochemistry, respectively. Relationships between immunohistochemical scores and several clinicopathological variables were also examined. Results Expression of NOB1 mRNA and protein in papillary thyroid carcinomatissue was significantly higher than in normal thyroid tissue and benign thyroid tissue, while there was no significant difference between normal thyroid tissue and benign thyroid tumour tissue. A high level of NOB1 protein expression was associated with large tumour size and Union for International Cancer Control stage, but was not significantly correlated with sex or age. Conclusions Compared with normal thyroid and benign thyroid tumour tissue, papillary thyroid carcinomas showed higher expression of NOB1, which indicates that the expression level of the NOB1 gene in the thyroid may play a key role in the occurrence and development of papillary thyroid carcinoma.
Efficacy and safety of a 14-day administration of tolvaptan in the treatment of patients with ascites in hepatic oedema
Authors: Sakaida Isao , Yamashita Satoyoshi , Kobayashi Tomoo , Komatsu Masafumi , Sakai Terufumi , Komorizono Yasuji , Okada Mitsuru , Okita Kiwamu ,   For the ASCITES 14-Day Administration Study Group
Published: May 2013

Objective To investigate the efficacy and safety of 14 days’ orally administered tolvaptan as adjunctive treatment for hepatic oedema in Japanese liver cirrhosis patients with insufficient response to conventional diuretics, with the option to increase dose in those who did not respond initially. Methods This multicentre, single-arm, phase 3 study allocated patients with liver cirrhosis and persistent ascites to 7-day treatment with 7.5 mg/day tolvaptan followed by an additional 7 days’ treatment. Responders at day 7 (achieving ≥1 kg body-weight reduction) continued on 7.5 mg/day tolvaptan; nonresponders (<1 kg body-weight reduction) received 15 mg/day tolvaptan. Conventional diuretic treatment continued throughout. The primary endpoint was change in body weight from baseline, as a marker of ascites volume. Results A total of 51 patients received 7.5 mg/day tolvaptan for 7 days, which caused a significant reduction in mean body weight (55% response rate). During the second 7-day treatment period, 30 patients received 7.5 mg/day tolvaptan and 13 patients received tolvaptan 15 mg/day: response rates were 43% and 23%, respectively. Two serious adverse events were observed. Serum sodium was within normal range. Conclusions Tolvaptan therapy for 14 days (with possible dose increase as necessary), in combination with conventional diuretics, effectively reduced body weight in patients with hepatic oedema.
Influence of laparoscopic carbon dioxide pneumoperitoneum on neonate circulation and respiration
Authors: Li Li-Wei , Zhang Wei , Ai Yan-Qiu , Li Li , Peng Zhou-Quan , Wang Hong-Wei 
Published: May 2013

Objective This study investigated the influence of laparoscopic carbon dioxide (CO2) pneumoperitoneum on neonate circulation and respiration. Methods The study included neonates undergoing elective laparoscopic abdominal surgery. CO2 insufflation pressure was maintained within 8–14 mmHg for pneumoperitoneum creation. Heart rate (HR), mean arterial pressure (MAP), peripheral oxygen saturation (SpO2), partial pressure of end-tidal carbon dioxide ( PETCO2) and maximum inspiratory pressure were monitored continuously. Arterial blood samples were collected: 5 min before pneumoperitoneum creation (baseline); 5, 10, and 20 min after CO2 insufflation; 10 min after CO2 exsufflation; 10 min after surgery. pH, partial pressure of CO2 (PaCO2) and arterial oxygen saturation (SaO2) were also measured. Results Thirty-six neonates were included. HR and MAP significantly increased after pneumoperitoneum creation, then decreased to baseline after CO2 exsufflation. PaCO2 and PETCO2 were significantly higher after pneumoperitoneum creation, whereas pH was significantly lower 20 min after pneumoperitoneum creation compared with baseline. No significant differences were observed in SpO2 and SaO2. Conclusion CO2 pneumoperitoneum had a significant effect on neonatal circulation and respiration, suggesting that the pneumoperitoneal pressure should be limited within a certain range in neonates undergoing laparoscopic surgery.