bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of the MD Anderson Symptom Inventory—Head-and-Neck—Filipino (MDASI—HN—F): clinical utility of symptom screening among patients with head-and-neck cancer
Authors: Bacorro Warren R , Sy Ortin Teresa T , Suarez Consuelo G , Mendoza Tito R , Que Jocelyn C 
Published: May 2015

ContextSymptom burden and quality of life (QOL) are of particular importance in head-and-neck cancer treatment. The MD Anderson Symptom Inventory—Head-and-Neck (MDASI-HN) is a simple symptom assessment tool practicable for patient follow-up, but a validated Filipino translation was previously unavailable.ObjectivesThe objectives of this study were to develop a valid Filipino translation of the MDASI-HN, to test the sensitivity of the validated MDASI core-F, and to report the prevalence and pattern of head-and-neck symptoms in our cohort.MethodsAn MDASI-HN-Filipino (MDASI-HN-F) version was developed and examined for convergent validity, internal consistency, test-retest reliability, known-group validity and sensitivity to change. Eligible participants were aged 18–80 years, with histopathologically-proven head-and-neck (except thyroid) cancer, able to understand and read English and Filipino, and without cognitive impairment or other conditions precluding self-administration of the questionnaire.ResultsParticipants (n=100) were aged 18–76 years; the majority were aged <60, male, married, had college schooling, or were from a Tagalog-speaking region. The validity of the MDASI HN-F was demonstrated in all parameters. Age or educational attainment did not affect convergent validity or test-retest reliability. At baseline, 48% had multiple moderate/severe symptoms and 38% had at least one severe symptom.ConclusionsThe MDASI-HN-F is valid, reliable and sensitive. The sensitivity of the MDASI core-F is demonstrated, and its validity and reliability reaffirmed. Moderate and severe head-and-neck symptoms are prevalent in early-stage and advanced-stage head-and-neck cancers, reflecting the utility of symptom screening for improvement of symptom management, QOL and compliance to treatment.
A multisource feedback tool to assess ward round leadership skills of senior paediatric trainees: (1) Development of tool
Authors: Lakshminarayana Indumathy , Wall David , Bindal Taruna , Goodyear Helen M 
Published: May 2015

ABSTRACTBackgroundLeading a ward round is an essential skill for hospital consultants and senior trainees but is rarely assessed during training.ObjectivesTo investigate the key attributes for ward round leadership and to use these results to develop a multisource feedback (MSF) tool to assess the ward round leadership skills of senior specialist trainees.MethodsA panel of experts comprising four senior paediatric consultants and two nurse managers were interviewed from May to August 2009. From analysis of the interview transcripts, 10 key themes emerged. A structured questionnaire based on the key themes was designed and sent electronically to paediatric consultants, nurses and trainees at a large university hospital (June–October 2010).Results81 consultants, nurses and trainees responded to the survey. The internal consistency of this tool was high (Cronbach's α 0.95). Factor analysis showed that five factors accounted for 72% of variance. The five key areas for ward round leadership were communication skills, preparation and organisation, teaching and enthusiasm, team working and punctuality; communication was the most important key theme. A MSF tool for ward round leadership skills was developed with these areas as five domains.ConclusionsWe believe that this tool will add to the current assessment tools available by providing feedback about ward round leadership skills.
Anti-inflammatory effects of PGE2 in the lung: role of the EP4 receptor subtype
Authors: Birrell Mark A , Maher Sarah A , Dekkak Bilel , Jones Victoria , Wong Sissie , Brook Peter , Belvisi Maria G 
Published: May 2015

BackgroundAsthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases of the airway. Current treatment options (long acting β-adrenoceptor agonists and glucocorticosteroids) are not optimal as they are only effective in certain patient groups and safety concerns exist regarding both compound classes. Therefore, novel bronchodilator and anti-inflammatory strategies are being pursued. Prostaglandin E2 (PGE2) is an arachidonic acid-derived eicosanoid produced by the lung which acts on four different G-protein coupled receptors (EP1–4) to cause an array of beneficial and deleterious effects. The aim of this study was to identify the EP receptor mediating the anti-inflammatory actions of PGE2 in the lung using a range of cell-based assays and in vivo models.Methods and resultsIt was demonstrated in three distinct model systems (innate stimulus, lipopolysaccharide (LPS); allergic response, ovalbumin (OVA); inhaled pollutant, cigarette smoke) that mice missing functional EP4 (Ptger4−/−) receptors had higher levels of airway inflammation, suggesting that endogenous PGE2 was suppressing inflammation via EP4 receptor activation. Cell-based assay systems (murine and human monocytes/alveolar macrophages) demonstrated that PGE2 inhibited cytokine release from LPS-stimulated cells and that this was mimicked by an EP4 (but not EP1–3) receptor agonist and inhibited by an EP4 receptor antagonist. The anti-inflammatory effect occurred at the transcriptional level and was via the adenylyl cyclase/cAMP/ cAMP-dependent protein kinase (PKA) axis.ConclusionThis study demonstrates that EP4 receptor activation is responsible for the anti-inflammatory activity of PGE2 in a range of disease relevant models and, as such, could represent a novel therapeutic target for chronic airway inflammatory conditions.
Particle creation in global de Sitter space: Bulk space consideration
Authors: Tanhayi M. Reza 
Published: May 2015

Recently in [P. R. Anderson and E. Mottola, Phys. Rev. D 89 (2014) 104039, arXiv:1310.1963 [gr-qc] and P. R. Anderson and E. Mottola, Phys. Rev. D 89 (2014) 104038, arXiv:1310.0030 [gr-qc].], it was shown that global de Sitter space is unstable even to the massive particle creation with no self-interactions. In this paper, we study the instability by making use of the coordinate-independent plane wave in de Sitter space. Within this formalism, we show that the previous results of instability of de Sitter space due to the particle creation can be generalized to higher-spin fields in a straightforward way. The so-called plane wave is defined globally in de Sitter space and de Sitter invariance is manifest since such modes are deduced from the group theoretical point of view by means of the Casimir operators. In fact, we employ the symmetry of embedding space namely the 4 + 1-dimensional flat space to write the field equations and the solutions can be obtained in terms of the plane wave in embedding space.
Abstract 3434: Genomic exome DNA sequencing identifies top driver genetic alterations in head and neck cancer cell lines of different HPV status
Authors: Cheng Hui , Yang Xinping , Si Han , Saleh Anthony , Coupar Jamie , Ferris Robert L. , Yarbrough Wendell G. , Prince Mark E. , Carey Thomas E. , Waes Carter Van , Chen Zhong 
Published: May 2015

Abstract
Head and neck squamous cell carcinoma (HNSCC) is among the top cancer types with high frequencies of genetic alterations, including mutation and copy number variation (CNV). The Cancer Genome Atlas (TCGA) has characterized 279 HNSCC tumors to provide a landscape of comprehensive genomic alterations. To identify cell line models which mimic HNSCC subtypes of genetic alterations, we have conducted genome-wide exome DNA sequencing (exome DNA-seq) and whole transcriptome sequencing (RNA-seq) on 16 HPV negative and 8 HPV positive HNSCC lines, in comparison with three normal human oral mucosa lines and 8 matched blood samples. Exome DNA-seq and RNA-seq were performed using an ABI SOLiD sequencer, and the data were analyzed with LifeScope2.5 and an in-house developed computation program. An average of 87X coverage in each cell line was achieved by exome DNA-seq. Deleterious mutations that negatively affect protein function were identified in each cell line using ANNOVAR software, in combination with multiple functional prediction tools, such as SIFT, PolyPhen-2, Likelihood Ratio Test (LRT), MutationTaster and MutationAssessor. The top deleterious mutations include TP53 in 42% of cell lines (56% in HPV- and 13% in HPV+ cell lines), and FAT1 and NOTCH1 mutations in 83% and 42% cell lines, respectively. These mutations are cross-validated through RNA-seq, which has an average of 168 million mapped reads with an estimated mean of 44X coverage per sample. In addition, we identified 261 putative CNV calls using the CoNIFER (copy number inference from exome reads) analysis. Among these putative CNV calls, 12 of them occur inside of the over 30 significant somatic copy number alteration (SCNA) sites identified in TCGA, including amplification of FADD, BIRC2/3, YAP1 and TP63. Our sequencing results identified the HNSCC cell lines with specific genetic alterations, which resemble many defects found from tumor specimens in TCGA project. These cell lines provided experimental models, which are amenable for future investigation of molecular mechanisms and targeted therapy, and could benefit preclinical drug evaluation and provide rationales for future clinical trials with genetic testing.
Supported by NIDCD intramural projects ZIA-DC-000016, 73 and 74.
Citation Format: Hui Cheng, Xinping Yang, Han Si, Anthony Saleh, Jamie Coupar, Robert L. Ferris, Wendell G. Yarbrough, Mark E. Prince, Thomas E. Carey, Carter Van Waes, Zhong Chen. Genomic exome DNA sequencing identifies top driver genetic alterations in head and neck cancer cell lines of different HPV status. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3434. doi:10.1158/1538-7445.AM2014-3434
Abstract 3447: Role of fibroblast growth factor receptors in esophageal squamous cell carcinoma
Authors: Shimada Yutaka , Okumura Tomoyuki , Nagata Takuya , Takei Yoshinori , Tsukada Kazuhiro , Shimizu Kazuharu 
Published: May 2015

Abstract
Introduction:
MicroRNA-210 regulates cancer cell proliferation by targeting fibroblast growth factor receptor-like 1 (FGFRL1) in esophageal squamous cell cancer (ESCC) (JBC 2011). The expression of FGFRL1 has been associated with tumor growth and lymph node metastasis. In the present study, we analyzed and compared the expression of FGFR1, FGFR2, FGFR3, and FGFR4 with that of FGFRL1 using a tissue microarray. We also examined whether antibodies for FGFRL1 inhibited the growth and motility of ESCC cells.
Material and Methods:
A squamous cell carcinoma tissue microarray established in Toyama University was used to evaluate the expression of the 5 FGFRs. Sixty-nine specimens of ESCC were obtained from 62 male and 7 female patients, with an average age of 64.4 years old, that underwent surgery between 1990 and 2008. The TNM stages of these patients were as follows; stage 1: 7, stage 2a; 10, stage 2b; 10, stage 3; 35, stage 4; 7. The immunohistochemical results of these patients were scored according to intensity and distribution after a careful examination by two independent researchers. The ESCC cell line KYSE520 was used for experimental analyses. Polyclonal and monoclonal antibodies for FGFRL1 were used to evaluate the function of FGFRL1.
Results:
The percentage of patients who tested positive for the expression of the different FGFRs was as follows: FGFRL-1, 81% (56/69); FGFR1, 65% (37/57); FGFR2, 36% (22/61); FGFR3, 21% (12/57); FGFR4, 39% (22/56). The prognosis of FGFRL1 positive patients was significantly worse than that of FGFRL1 negative patients. (P=0.0311). Both polyclonal and monoclonal antibodies inhibited the growth (50% reduction) and motility (25% reduction) of ESCC cells. However, no association was observed between the expression of the other FGFRs and patient prognosis. Regarding combination analysis of the expression of each FGFR, patients that co-expressed FGFRL1 and FGFR1 had the worst prognosis, while patients who tested negative for the expression of both FGFRL1 and FGFR4 had the best prognosis.
Conclusions:
Among the 5 FGFRs, the expression of FGFRL1 was the main oncogenic driving factor in ESCC patients. The expression of FGFR1 and FGFR4 may be a sub-driving factor of ESCC.
Citation Format: Yutaka Shimada, Tomoyuki Okumura, Takuya Nagata, Yoshinori Takei, Kazuhiro Tsukada, Kazuharu Shimizu. Role of fibroblast growth factor receptors in esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3447. doi:10.1158/1538-7445.AM2014-3447
Abstract 3464: The effect of EPO-receptor in estrogen receptor positive breast cancer
Authors: Vaapil Marica C. , Reinbothe Susann , Larsson Anna-Maria , Wigerup Caroline , Sun Jianmin , Jögi Annika , Neumann Drorit , Rönnstrand Lars , Påhlman Sven 
Published: May 2015

Abstract
The main function of Erythropoietin (EPO) and its receptor (EPOR) is the stimulation of erythropoiesis. Recombinant human EPO (rhEPO) is therefore used to treat anemia in cancer patients. However, recent clinical trials have indicated that rhEPO treatment might promote tumor progression and have a negative effect on patient survival. In addition, EPOR expression has been detected in several cancer forms. Using a newly produced anti-EPOR antibody that reliably detects the full-length isoform of the EPOR we show that breast cancer tissue and cells express the EPOR protein. rhEPO stimulation of cultured EPOR expressing breast cancer cells did not result in increased proliferation, overt activation of EPOR (receptor phosphorylation) or a consistent activation of canonical EPOR signaling pathway mediators such as JAK2, STAT3, STAT5, or AKT. However, EPOR knockdown experiments suggested functional EPO receptors in estrogen receptor positive (ERα+) breast cancer cells, as reduced EPOR expression resulted in decreased proliferation. This effect on proliferation was not seen in ERα negative cells. EPOR knockdown decreased ERα activity in ERα+ breast cancer cells and diminished ERα+ phosphorylation on Ser118, results that further support a mechanism by which EPOR affects proliferation via ERα+ mediated mechanisms. In conclusion, we show that EPOR protein is expressed in breast cancer cells, where it appears to promote proliferation in ERα+ expressing breast cancer cells, in part via its capacity to positively modulate ERα activity.
Citation Format: Marica C. Vaapil, Susann Reinbothe, Anna-Maria Larsson, Caroline Wigerup, Jianmin Sun, Annika Jögi, Drorit Neumann, Lars Rönnstrand, Sven Påhlman. The effect of EPO-receptor in estrogen receptor positive breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3464. doi:10.1158/1538-7445.AM2014-3464
Abstract 3468: Integrin-β6 is required for transforming growth factor (TGF)-β-mediated epithelial-mesenchymal transition (EMT) and promotes the disease progression of intrahepatic cholangiocellular carcinoma
Authors: Higashi Takaaki , Hayashi Hiromitu , Kuroki Hideyuki , Nakagawa Shigeki , Sakamoto Keita , Nitta Hidetoshi , Chikamoto Akira , Toru Toru , Baba Hideo 
Published: May 2015

Abstract
Background: Intrahepatic cholangiocellular carcinoma (ICC) is characterized as a poor prognostic disease represented by the highly invasiveness. Epithelial-mesenchymal transition (EMT) plays a pivotal role in cancer invasion and metastasis, and then TGF-β signaling is a potent inducible factor of EMT. Integrin-β6, which is an epithelial restricted trans-membrane protein, promotes binding to extracellular matrix proteins (fibronectin, vitronectin and tenascin) facilitating cell migration and activates TGFβ1 via binding to the latency associated peptide (LAP) of the TGF-β complex during embryogenesis and wound healing. In this study, we investigated the role of integrin-β6 during TGF-β-mediated EMT using ICC cell lines, and examined the clinic-pathological significance of Integrinβ6 expression in ICC patients.
Material and Methods: We measured integrin-β6 mRNA expression by real time PCR using 7 ICC cell lines (Hucct1, HuH28, OZ, RBE, Ssp25, TFK1, Ysccc). To examine the role of integrin-β6 during TGF-β-mediated EMT in ICC cell lines, we downregulated integrin-β6 expression by RNAi during TGF-β-medaited EMT. Furthermore, using 55 resected ICC specimens, we evaluated integrin-β6 expression by immunohistochemical staining.
Results: Of 7 ICC cell lines, Ysccc and OZ cell lines revealed high integrin-β6 expressions. Addition of TGF-β to Ysccc cell successfully induced EMT, characterized by the upregulated vimentin expression, downregulated E-cadherin expression, spindle-shaped morphology, and high invasiveness, with the integrin-β6 induction. The inhibition of integrin-β6 expression using RNAi abolished TGF-β-mediated EMT induction. In clinical setting, high integrin-β6 expression was significantly associated with Stage IV, lymph node metastasis, and blood vessel invasion, and then resulted in worse prognosis compared with low expression group.
Conclusion : Integrin-β6 is required for TGF-β-mediated EMT and promotes the disease progression of ICC.
Citation Format: Takaaki Higashi, Hiromitu Hayashi, Hideyuki Kuroki, Shigeki Nakagawa, Keita Sakamoto, Hidetoshi Nitta, Akira Chikamoto, Toru Toru, Hideo Baba. Integrin-β6 is required for transforming growth factor (TGF)-β-mediated epithelial-mesenchymal transition (EMT) and promotes the disease progression of intrahepatic cholangiocellular carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3468. doi:10.1158/1538-7445.AM2014-3468
Abstract 3469: The effect of TGF-beta on matrix metalloproteinase-2, 9, and 13 expression and secrection in human prostate cancer cells
Authors: Cao Yang , Bolton Clement J. , Khan Shafiq A. 
Published: May 2015

Abstract
Matrix metalloproteinases (MMPs) are major critical molecules assisting tumor cells during metastasis. The production of MMPs by prostatic epithelial and/or neighboring stromal cells plays an important role in the penetration of extracellular matrix barriers in normal or neoplastic growth. Activation of MMP-13 is critical in the MMP cascade and MMP-2 and -9 are important in tumor metastasis. Transforming growth factor (TGF)-beta has been reported to exert growth inhibitory activity in normal epithelial cells whereas it induces cell proliferation and invasive phenotypes in advanced carcinomas.
In this study, we investigated the role of TGF-β1 and TGF-β3 in MMP expression and secretion in prostate cancer cell line PC-3 and prostatic epithelial cell line RWPE-1. Treatment with 1ng/ml of TGF-β1 and TGF-β3 enhanced MMP-9 expression in both cell lines but showed no significant effect on MMP-2 expression. TGF-β1 and TGF-β3 increased MMP-13 expression in PC-3 cells at 8 hr but decreased its expression in RWPE-1 cells. As examined in conditioned medium (CM) by zymography, TGF-β1 and TGF-β3 increased the secretion of pro-MMP-9 and its active form at different time points in PC-3cells. However, they inhibited pro-MMP-2 and no active MMP-2 activity was detected in the same CM. On the other hand, both TGF-β1 and TGF-β3 increased pro-MMP-9 and pro-MMP-2 in RWPE-1 cells. TGF-β3 is more potent that TGF-β1. TGF-β3 also increased active MMP-2 after 18 hr. MMP-9 siRNA abolished TGF-β induced invasion in PC-3 cells but MMP-13 siRNA didn’t affect PC3 cell migration. Our results suggest that TGF-β1 and TGF-β3 have stimulatory effects on MMP-9 secretion in both PC-3 and RWPE-1cells and similar effect on MMP-2 secretion in RWPE-1 cells. However, they have inhibitory effect on MMP-2 secretion in PC-3 cells. MMP-9 is essential for TGF-β effects on cell migration. TGF-β has opposite effect on MMP-13 expression in the two cell lines and MMP-13 is not required for cell migration.
Citation Format: Yang Cao, Clement J. Bolton, Shafiq A. Khan. The effect of TGF-beta on matrix metalloproteinase-2, 9, and 13 expression and secrection in human prostate cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3469. doi:10.1158/1538-7445.AM2014-3469
Abstract 347: Dasatinib accelerates valproic acid-induced acute myeloid leukemia cells death by regulation of differentiation capacity
Authors: Heo Sook-Kyoung , Noh Eui-Kyu , Yoon Dong-Joon , Jo Jae-Cheol , Park Jae-Hoo , Kim Hawk 
Published: May 2015

Abstract
Dastinib (BMS-354825) is a FDA-approved small compound that was developed for chronic myeloid leukemia as a multi-targeted kinase inhibitor of wild-type BCR-ABL and SRC family kinases. Valproic acid (VPA; Orfiril) has been a well-known anti-epileptic drug worldwidely, and belong to the class I histone deacetylase inhibitor. The aim of this research is to determine the anti-leukemic effects of combination of dasatinib and VPA or their mechanism in acute myeloid leukemia (AML) cells. In this study, dasatinib showed potent inhibitory effects on VPA-treated AML cells that were associated with induced G1 phase cell cycle arrest and also apoptosis including the cleavage of PARP, caspase-3, -7 and -9. Moreover, inhibitors of caspase-3 and -9 (Z-DEVD-FMK and LEHD-CHO) efficiently inhibited dasatinib-induced apoptosis in VPA-treated AML cells. Therefore, dasatinib/VPA-induced cell death occurred via caspase-dependent apoptosis. Also, inhibitors of MEK/ERK (U0126 and PD98059) and p38 MAPK (SB203580) efficiently inhibited dasatinib/VPA-induced apoptosis. The combination of dasatinib and VPA differentiation capacity of AML cells is more powerful than each drug alone. So the combination is enough to push AML cells to death strongly by G1 cell cycle arrest and caspase-dependent apoptosis. In addition, MEK/ERK and p38 MAPK controls dasatinib/VPA-induced apoptosis as an upstream regulator. Finally, co-treatment of dasatinib and VPA is contributed to AML cell death by regulation of differentiation capacity. Taken together, these results indicate that dasatinib and VPA together have a potential for anti-leukemic therapy.
Citation Format: Sook-Kyoung Heo, Eui-Kyu Noh, Dong-Joon Yoon, Jae-Cheol Jo, Jae-Hoo Park, Hawk Kim. Dasatinib accelerates valproic acid-induced acute myeloid leukemia cells death by regulation of differentiation capacity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 347. doi:10.1158/1538-7445.AM2014-347