bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the clinical efficacy of minimally invasive procedures for breast cancer screening at a teaching hospital
Authors: Verenhitach Beatriz Daou , Elias Simone , Patrocínio Ana Claudia , Nazário Afonso Celso Pinto , Waizberg Angela 
Published: June 2011

AimsTo assess the clinical efficacy of diagnostic procedures for breast cancer at a teaching hospital using internal auditing tools and quality control measures.MethodsA retrospective assessment of 500 patients who underwent core needle biopsy (wide-bore needle biopsy; WBN) of palpable or non-palpable breast nodes that were submitted for at least one cytological examination (fine needle aspiration (FNA) cytology and/or imprint of a WBN specimen). For statistical analysis the auditing tool and quality control proposed by the National Health Service breast screening programme was utilised.ResultsFor FNA, full specificity, positive predictive value, inadequate rates and suspicious rates were satisfactory while absolute sensitivity, complete sensitivity, false negatives and false positives were unsatisfactory. For imprint, absolute sensitivity, complete sensitivity, inadequate rate from cancers and suspicious rates were satisfactory, and the remaining indicators were unsatisfactory. WBN displayed the best performance with absolute sensitivity, complete sensitivity, false negative, suspicious rates, full specificity and predictive value showing satisfactory results and only one unsatisfactory result (false positive).ConclusionsBased on an overall analysis, WBN displayed the highest clinical efficacy compared with FNA and imprint, and demonstrated adequate safety for confirming the appropriate diagnosis and management of patients, ensuring the efficacy of the service.
Locked nucleic acid probes for enhanced detection of FLT3 D835/I836, JAK2 V617F and NPM1 mutations
Authors: Warshawsky Ilka , Mularo Frank 
Published: June 2011

AimsDetecting low-level clinically significant cancer-relevant somatic mutations can be difficult. Several technologies exist for detecting minority mutations. One method is locked nucleic acid (LNA) PCR. In this study, LNA probes were used to enhance the sensitivity for detecting FLT3 D835/I836 tyrosine kinase domain (TKD) mutations, the JAK2 V617F mutation and insertion mutations in the nucleophosmin 1 gene.MethodsPCR was performed with and without LNA probes using DNA known to contain FLT3 D835/I836 TKD, JAK2 V617F and NPM1 mutations. FLT3 D835/I836 TKD mutations were detected following EcoRV restriction enzyme digestion and capillary electrophoresis. The JAK2 V617F mutation was detected by melt-curve analysis. NPM1 insertions were detected by capillary electrophoresis.ResultsThe detection of FLT3 D835/I836, JAK2 V617F and NPM1 mutations was enhanced approximately 10–50-fold using LNA probes. Rare JAK2 double mutants gave abnormal blocking patterns with the LNA probe.ConclusionsAdding LNA probes to existing assays is a simple way to enhance and confirm the detection of mutations, especially those at low levels.
MicroRNA-199a-3p Is Downregulated in Human Osteosarcoma and Regulates Cell Proliferation and Migration
Authors: Duan Zhenfeng , Choy Edwin , Harmon David , Liu Xianzhe , Susa Michiro , Mankin Henry , Hornicek Francis 
Published: June 2011

Abstract
microRNAs (miRNA, miR) play an important role in cancer cell growth and migration; however, the potential roles of miRNAs in osteosarcoma remain largely uncharacterized. By applying a miRNA microarray platform and unsupervised hierarchical clustering analysis, we found that several miRNAs have altered expression levels in osteosarcoma cell lines and tumor tissues when compared with normal human osteoblasts. Three miRNAs, miR-199a-3p, miR-127-3p, and miR-376c, were significantly decreased in osteosarcoma cell lines, whereas miR-151-3p and miR-191 were increased in osteosarcoma cell lines in comparison with osteoblasts. Transfection of precursor miR-199a-3p into osteosarcoma cell lines significantly decreased cell growth and migration, thus indicating that the inhibition effect is associated with an increase in the G1-phase and a decrease of the S-phase cell population. In addition, we observed decreased mTOR and Stat3 expression in miR-199a-3p transfected cells. This study provides new insights for miRNAs in osteosarcoma and suggests that miR-199a-3p may play a functional role in osteosarcoma cell growth and proliferation. Restoring miR-199a-3p's function may provide therapeutic benefits in osteosarcoma. Mol Cancer Ther; 10(8); 1337–45. ©2011 AACR.
Notch1 Inhibition Alters the CD44hi/CD24lo Population and Reduces the Formation of Brain Metastases from Breast Cancer
Authors: McGowan Patricia M. , Simedrea Carmen , Ribot Emeline J. , Foster Paula J. , Palmieri Diane , Steeg Patricia S. , Allan Alison L. , Chambers Ann F. 
Published: June 2011

Abstract
Brain metastasis from breast cancer is an increasingly important clinical problem. Here we assessed the role of CD44hi/CD24lo cells and pathways that regulate them, in an experimental model of brain metastasis. Notch signaling (mediated by γ-secretase) has been shown to contribute to maintenance of the cancer stem cell (CSC) phenotype. Cells sorted for a reduced stem-like phenotype had a reduced ability to form brain metastases compared with unsorted or CD44hi/CD24lo cells (P &lt; 0.05; Kruskal–Wallis). To assess the effect of γ-secretase inhibition, cells were cultured with DAPT and the CD44/CD24 phenotypes quantified. 231-BR cells with a CD44hi/CD24lo phenotype was reduced by about 15% in cells treated with DAPT compared with DMSO-treated or untreated cells (P = 0.001, ANOVA). In vivo, mice treated with DAPT developed significantly fewer micro- and macrometastases compared with vehicle treated or untreated mice (P = 0.011, Kruskal–Wallis). Notch1 knockdown reduced the expression of CD44hi/CD24lo phenotype by about 20%. In vitro, Notch1 shRNA resulted in a reduction in cellular growth at 24, 48, and 72 hours time points (P = 0.033, P = 0.002, and P = 0.009, ANOVA) and about 60% reduction in Matrigel invasion was observed (P &lt; 0.001, ANOVA). Cells transfected with shNotch1 formed significantly fewer macrometastases and micrometastases compared with scrambled shRNA or untransfected cells (P &lt; 0.001; Kruskal–Wallis). These data suggest that the CSC phenotype contributes to the development of brain metastases from breast cancer, and this may arise in part from increased Notch activity. Mol Cancer Res; 9(7); 834–44. ©2011 AACR.
Circulating Tumor Cells from Patients with Advanced Prostate and Breast Cancer Display Both Epithelial and Mesenchymal Markers
Authors: Armstrong Andrew J. , Marengo Matthew S. , Oltean Sebastian , Kemeny Gabor , Bitting Rhonda L. , Turnbull James D. , Herold Christina I. , Marcom Paul K. , George Daniel J. , Garcia-Blanco Mariano A. 
Published: June 2011

Abstract
During cancer progression, malignant cells undergo epithelial-mesenchymal transitions (EMT) and mesenchymal-epithelial transitions (MET) as part of a broad invasion and metastasis program. We previously observed MET events among lung metastases in a preclinical model of prostate adenocarcinoma that suggested a relationship between epithelial plasticity and metastatic spread. We thus sought to translate these findings into clinical evidence by examining the existence of EMT in circulating tumor cells (CTC) from patients with progressive metastatic solid tumors, with a focus on men with castration-resistant prostate cancer (CRPC) and women with metastatic breast cancer. We showed that the majority (&gt;80%) of these CTCs in patients with metastatic CRPC coexpress epithelial proteins such as epithelial cell adhesion molecule (EpCAM), cytokeratins (CK), and E-cadherin, with mesenchymal proteins including vimentin, N-cadherin and O-cadherin, and the stem cell marker CD133. Equally, we found that more than 75% of CTCs from women with metastatic breast cancer coexpress CK, vimentin, and N-cadherin. The existence and high frequency of these CTCs coexpressing epithelial, mesenchymal, and stem cell markers in patients with progressive metastases has important implications for the application and interpretation of approved methods to detect CTCs. Mol Cancer Res; 9(8); 997–1007. ©2011 AACR.
The N-Terminal Domain of G3BP Enhances Cell Motility and Invasion by Posttranscriptional Regulation of BART
Authors: Taniuchi Keisuke , Nishimori Isao , Hollingsworth Michael A. 
Published: June 2011

Abstract
The regulation of mRNA stability plays an important role in the control of gene expression during cell motility and invasion. We previously reported that GTPase-activating protein [Src homology 3 (SH3) domain] binding protein (G3BP), a marker of cytoplasmic stress granules that are formed in stressed cells and regulate mRNA stability, binds and degrades the mRNA of binder of Arl two (BART) that inhibits retroperitoneal invasion and hepatic metastasis of pancreatic cancer cells. Here, we report that overexpression of the amino (N)-terminal region of G3BP, including the binding region for BART mRNA, dominant-negatively inhibits formation of the complex between endogenous G3BP and BART mRNA, and increases the expression of BART. This, in turn, inhibits the invasiveness of pancreatic cancer cells. On the other hand, the carboxy (C)-terminal region of G3BP is associated with phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) that initiates stress granule assembly but does not modulate the posttranscriptional regulation of BART mRNA. N-terminal G3BP also plays a role in regulating secreted matrix metalloproteinases, transcription factors, and a variety of genes involved in cell adhesion and motility. These results suggest that N-terminal G3BP contributes to posttranscriptional regulation of cell motility and invasive capacity of pancreatic cancer. Mol Cancer Res; 9(7); 856–66. ©2011 AACR.
Control of VEGF Expression in Triple-Negative Breast Carcinoma Cells by Suppression of SAF-1 Transcription Factor Activity
Authors: Ray Alpana , Dhar Srijita , Ray Bimal K. 
Published: June 2011

Abstract
Angiogenesis plays a significant role in cancer by providing increased blood supply to the affected tissues and thus bringing in growth factors, cytokines, and various nutrients for tumor growth. VEGF is the most prominent angiogenic agent that is markedly induced in cancer. Induction of VEGF has been widely studied but as cancer cells are quite adept at acquiring new alternative processes to circumvent surrounding environmental pressures, our understanding of the molecular mechanisms regulating VEGF expression in cancer, especially in triple-negative breast cancer cells, remains incomplete. Here, we present evidence of a novel mode of VEGF induction in triple-negative MDA-MB-231 breast cancer cells that is regulated by serum amyloid A activating factor 1 (SAF-1) transcription factor. Inhibition of SAF-1 by antisense short hairpin RNA profoundly reduces VEGF expression along with reduction in endothelial cell proliferation and migration. By both in vitro and in vivo molecular studies, we show that the effect of SAF-1 is mediated through its direct interaction with the VEGF promoter. In correlation, DNA-binding activity of SAF-1 is found to be significantly higher in MDA-MB-231 breast cancer cells. Examination of several breast cancer samples further revealed that SAF-1 is overexpressed in clinical breast cancer tissues. Taken together, these findings reveal that SAF-1 is a hitherto unrecognized participant in inducing VEGF expression in triple-negative breast cancer cells, an aggressive form of breast cancer that currently lacks effective treatment options. Suppression of SAF-1 activity in these cells can inhibit VEGF expression, providing a possible new method to control angiogenesis. Mol Cancer Res; 9(8); 1030–41. ©2011 AACR.
Fibroblast Growth Factor Receptor Mediates Fibroblast-Dependent Growth in EMMPRIN-Depleted Head and Neck Cancer Tumor Cells
Authors: Liu Zhiyong , Hartman Yolanda E. , Warram Jason M. , Knowles Joseph A. , Sweeny Larissa , Zhou Tong , Rosenthal Eben L. 
Published: June 2011

Abstract
Head and neck squamous cell carcinoma tumors (HNSCC) contain a dense fibrous stroma which is known to promote tumor growth, although the mechanism of stroma-mediated growth remains unclear. As dysplastic mucosal epithelium progresses to cancer, there is incremental overexpression of extracellular matrix metalloprotease inducer (EMMPRIN) which is associated with tumor growth and metastasis. Here, we present evidence that gain of EMMPRIN expression allows tumor growth to be less dependent on fibroblasts by modulating fibroblast growth factor receptor-2 (FGFR2) signaling. We show that silencing EMMPRIN in FaDu and SCC-5 HNSCC cell lines inhibits cell growth, but when EMMPRIN-silenced tumor cells were cocultured with fibroblasts or inoculated with fibroblasts into severe combined immunodeficient mice, the growth inhibition by silencing EMMPRIN was blunted by the presence of fibroblasts. Coculture experiments showed fibroblast-dependent tumor cell growth occurred via a paracrine signaling. Analysis of tumor gene expression revealed expression of FGFR2 was inversely related to EMMPRIN expression. To determine the role of FGFR2 signaling in EMMPRIN-silenced tumor cells, ligands and inhibitors of FGFR2 were assessed. Both FGF1 and FGF2 enhanced tumor growth in EMMPRIN-silenced cells compared with control vector–transfected cells, whereas inhibition of FGFR2 with blocking antibody or with a synthetic inhibitor (PD173074) inhibited tumor cell growth in fibroblast coculture, suggesting the importance of FGFR2 signaling in fibroblast-mediated tumor growth. Analysis of xenografted tumors revealed that EMMPRIN-silenced tumors had a larger stromal compartment compared with control. Taken together, these results suggest that EMMPRIN acquired during tumor progression promotes fibroblast-independent tumor growth. Mol Cancer Res; 9(8); 1008–17. ©2011 AACR.
Determination of Inadvertent Atrial Capture During Para-Hisian Pacing
Authors: Obeyesekere Manoj , Leong-Sit Peter , Skanes Allan , Krahn Andrew , Yee Raymond , Gula Lorne J. , Bennett Matthew , Klein George J. 
Published: June 2011

Background—
Inadvertent capture of the atrium will lead to spurious results during para-Hisian pacing. We sought to establish whether the stimulation-to-atrial electrogram interval at the proximal coronary sinus (stim-PCS) or high right atrium (stim-HRA) could signal inadvertent atrial capture.

Methods and Results—

Para-Hisian pacing with and without intentional atrial capture was performed in 31 patients. Stim-HRA and stim-PCS intervals were measured with atrial capture, His plus para-Hisian ventricular (H+V) capture, and para-Hisian ventricular (V) capture alone. The mean stim-HRA interval was significantly shorter with atrial capture (66±18 ms) than with H+V (121±27 ms,
P
<0.001) or V capture alone (174±38 ms,
P
<0.001). The mean stim-PCS interval was significantly shorter with atrial capture (51±16 ms) than with H+V (92±22 ms,
P
<0.001) or V capture alone (146±33 ms,
P
<0.001). A stim-PCS <60 ms (stim-HRA <70 ms) was observed only with atrial capture. A stim-PCS >90 ms (stim-HRA >100 ms) was observed only in the absence of atrial capture. A stim-HRA of <85 ms was highly specific and stim-PCS of <85 ms highly sensitive at identifying atrial capture. Stim-HRA intervals of 75 to 97 ms and stim-PCS intervals of 65 to 88 ms were observed with either atrial, His, or para-Hisian ventricular capture without atrial capture. In this overlap zone, all patients demonstrated a stim-PCS or stim-HRA interval prolongation of at least 20 ms when the catheter was advanced to avoid deliberate atrial pacing. The QRS morphology was of limited value in distinguishing atrial capture due to concurrent ventricular or H+V capture, as observed in 20 of 31 (65%) patients.

Conclusions—
Stim-PCS and stim-HRA intervals can be used to monitor for inadvertent atrial capture during para-Hisian pacing. A stim-PCS <60 ms (or stim-HRA <70 ms) and stim-PCS >90 ms (or stim-HRA >100 ms) were observed only with and without atrial capture, respectively, but there was significant overlap between these values. Deliberate atrial capture and loss of capture reliably identifies atrial capture regardless of intervals.
Ablation of Ventricular Arrhythmias in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy
Authors: Bai Rong , Di Biase Luigi , Shivkumar Kalyanam , Mohanty Prasant , Tung Roderick , Santangeli Pasquale , Saenz Luis Carlos , Vacca Miguel , Verma Atul , Khaykin Yariv , Mohanty Sanghamitra , Burkhardt J. David , Hongo Richard , Beheiry Salwa , Dello Russo Antonio , Casella Michela , Pelargonio Gemma , Santarelli Pietro , Sanchez Javier , Tondo Claudio , Natale Andrea 
Published: June 2011

Background—
In patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy, freedom from ventricular arrhythmias (VAs) after endocardial ablation is limited. We compared the long-term freedom from recurrent VAs by using endocardial-alone ablation versus endo-epicardial substrate-based ablation.

Methods and Results—

Forty-nine patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy undergoing ablation of ventricular tachycardia (VT) were divided into 2 groups: endocardial-alone ablation (group 1, n=23) and endo-epicardial ablation (group 2, n=26). All patients had an implantable cardioverter-defibrillator (ICD). Conventional and 3D mappings were used to determine the mechanism of induced VTs and to identify area of “scar” or “abnormal” myocardium. All critical sites responsible for VTs and points with “abnormal” potential were targeted for ablation from endocardium (group 1) or from both endocardium and epicardium (group 2). The procedural end point was noninducibility of sustained, monomorphic VT with isoproterenol. The presence of frequent premature ventricular contractions at the end of ablation was recorded. Patients were followed up by ECG, Holter, and ICD interrogation. After a follow-up of at least 3 years, freedom from VAs or ICD therapy was 52.2% (12/23) in group 1 and 84.6% (22/26) in group 2 (
P
=0.029), with 21.7% (5/23) and 69.2% (18/26) patients off antiarrhythmic drugs (
P
<0.001), respectively. Compared with patients with no premature ventricular contractions after ablation, patients with frequent premature ventricular contractions after ablation were more likely to have VA recurrence/ICD therapy [3/33 (9%) versus 12/16 (75%); log-rank
P
<0.001].

Conclusions—
An endo-epicardial–based ablation strategy achieves higher long-term freedom from recurrent VAs off antiarrhythmic therapy in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy when compared with endocardial-alone ablation. The presence of ≥10 premature ventricular contractions per minute after ablation is associated with more VA recurrence.
Genome-Wide Significance and Replication of the Chromosome 12p11.22 Locus Near the
PTHLH
Gene for Peripartum Cardiomyopathy
Authors: Horne Benjamin D. , Rasmusson Kismet D. , Alharethi Rami , Budge Deborah , Brunisholz Kimberly D. , Metz Torri , Carlquist John F. , Connolly Jennifer J. , Porter T. Flint , Lappé Donald L. , Muhlestein Joseph B. , Silver Robert , Stehlik Josef , Park James J. , May Heidi T. , Bair Tami L. , Anderson Jeffrey L. , Renlund Dale G. , Kfoury Abdallah G. 
Published: June 2011

Background—
Peripartum (PP) cardiomyopathy (CM) is a rare condition of unknown etiology that occurs in late pregnancy or early postpartum. Initial evidence suggests that genetic factors may influence PPCM. This study evaluated and replicated genome-wide association of single nucleotide polymorphisms with PPCM.

Methods and Results—

Genome-wide single nucleotide polymorphisms in women with verified PPCM diagnosis (n=41) were compared separately with local control subjects (n=49 postmenopausal age-discordant women with parity ≥1 and no heart failure) and iControls (n=654 women ages 30 to 84 years with unknown phenotypes). A replication study of independent population samples used new cases (PPCM2, n=30) compared with new age-discordant control subjects (local2, n=124) and with younger control subjects (n=89) and obstetric control subjects (n=90). A third case set of pregnancy-associated CM cases not meeting strict PPCM definitions (n=29) was also studied. In the genome-wide association study, 1 single nucleotide polymorphism (rs258415) met genome-wide significance for PPCM versus local control subjects (
P
=2.06×10
−8
; odds ratio [OR], 5.96). This was verified versus iControls (
P
=7.92×10
−19
; OR, 8.52). In the replication study for PPCM2 cases, rs258415 (ORs are per C allele) replicated at
P
=0.009 versus local2 control subjects (OR, 2.26). This replication was verified for PPCM2 versus younger control subjects (
P
=0.029; OR, 2.15) and versus obstetric control subjects (
P
=0.013; OR, 2.44). In pregnancy-associated cardiomyopathy cases, rs258415 had a similar effect versus local2 control subjects (
P
=0.06; OR, 1.79), younger control subjects (
P
=0.14; OR, 1.65), and obstetric control subjects (
P
=0.038; OR, 1.99).

Conclusions—

Genome-wide association with PPCM was discovered and replicated for rs258415 at chromosome 12p11.22 near
PTHLH
. This study indicates a role of genetic factors in PPCM and provides a new locus for further pathophysiological and clinical investigation.
Translating Gender Justice in Southeast Asia: Situated Ethics, NGOs, and Bio-Welfare
Authors: Ong Aihwa 
Published: June 2011

AbstractThis essay shows that regardless of existing laws and prominent female leaders, gender justice as a value must be attuned to the situated ethics of the majority populations in order to gain social legitimacy. Since the 1980s, NGO movements for reformasi, or reform, and democrasi have intervened on women’s behalf in a variety of areas—Muslim feminism, political violence, and the abuse of maids, sex workers, and migrants. They have had to modify rights-based strategies in accordance with religious, legal, and economic conditions. Universalizing gender rights articulate situated fields of power that contest or qualify imposed regulatory systems of humanitarian values. It is important to acknowledge that gender justice intervenes in webs of power that can thwart its regulation as well as form new alliances of solidarity. Gender justice and rights cannot be unilaterally imposed, but are transmitted and translated through negotiations with situated religious and citizenship norms. In postcolonial milieus, ideals of gender justice interact with diverse ethical regimes to shape the conditions of possibility for problematizing gender and possible solutions to gender inequality that cannot be predetermined.