bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Compound, NK150460, Exhibits Selective Antitumor Activity against Breast Cancer Cell Lines through Activation of Aryl Hydrocarbon Receptor
Authors: Fukasawa Kazuteru , Kagaya Shigehide , Maruyama Sakiko , Kuroiwa Shunsuke , Masuda Kuniko , Kameyama Yoshio , Satoh Yoshitaka , Akatsu Yuichi , Tomura Arihiro , Nishikawa Kiyohiro , Horie Shigeo , Ichikawa Yuh-ichiro 
Published: December 2014

AbstractAntiestrogen agents are commonly used to treat patients with estrogen receptor (ER)–positive breast cancer. Tamoxifen has been the mainstay of endocrine treatment for patients with early and advanced breast cancer for many years. Following tamoxifen treatment failure, however, there are still limited options for subsequent hormonal therapy. We discovered a novel compound, NK150460, that inhibits 17β-estradiol (E2)–dependent transcription without affecting binding of E2 to ER. Against our expectations, NK150460 inhibited growth of not only most ER-positive, but also some ER-negative breast cancer cell lines, while never inhibiting growth of non–breast cancer cell lines. Cell-based screening using a random shRNA library, identified aryl hydrocarbon receptor nuclear translocator (ARNT) as a key gene involved in NK150460′s antitumor mechanism. siRNAs against not only ARNT but also its counterpart aryl hydrocarbon receptor (AhR) and their target protein, CYP1A1, dramatically abrogated NK150460′s growth-inhibitory activity. This suggests that the molecular cascade of AhR/ARNT plays an essential role in NK150460′s antitumor mechanism. Expression of ERα was decreased by NK150460 treatment, and this was inhibited by an AhR antagonist. Unlike two other AhR agonists now undergoing clinical developmental stage, NK150460 did not induce histone H2AX phosphorylation or p53 expression, suggesting that it did not induce a DNA damage response in treated cells. Cell lines expressing epithelial markers were more sensitive to NK150460 than mesenchymal marker-expressing cells. These data indicate that NK150460 is a novel AhR agonist with selective antitumor activity against breast cancer cell lines, and its features differ from those of the other two AhR agonists. Mol Cancer Ther; 14(2); 343–54. ©2014 AACR.
Combining Onartuzumab with Erlotinib Inhibits Growth of Non–Small Cell Lung Cancer with Activating EGFR Mutations and HGF Overexpression
Authors: Sano Yuji , Hashimoto Eri , Nakatani Noriaki , Abe Masaichi , Satoh Yasuko , Sakata Kiyoaki , Fujii Toshihiko , Fujimoto-Ouchi Kaori , Sugimoto Masamichi , Nagahashi Shigehisa , Aoki Masahiro , Motegi Hiroshi , Sasaki Eiichi , Yatabe Yasushi 
Published: December 2014

Abstract
Erlotinib, a tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI), benefits survival of patients with non–small cell lung cancer (NSCLC) who harbor activating EGFR mutations. However, elevated expression of hepatocyte growth factor (HGF), a ligand of the MET receptor tyrosine kinase, causes erlotinib resistance. Because onartuzumab, a monovalent antibody to MET, blocks HGF-induced MET activation, the addition of onartuzumab to erlotinib may improve therapeutic efficacy. We engineered the human NSCLC cell line PC-9 (MET-positive cells harboring an exon 19 deletion of EGFR) to overexpress hHGF and evaluated the effects of an onartuzumab and erlotinib combination in vitro and in vivo in xenograft models. A stable clone of PC-9/hHGF was less sensitive to erlotinib than the parental PC-9, and the addition of onartuzumab to erlotinib suppressed the proliferation of these cells in vitro. In PC-9/hHGF xenograft tumors, onartuzumab or erlotinib alone minimally inhibited tumor growth; however, combining onartuzumab and erlotinib markedly suppressed tumor growth. The total MET protein level was decreased in PC-9/hHGF cells, because MET is constitutively phosphorylated by autocrine HGF, leading to its ubiquitination and degradation. Onartuzumab reduced phospho-MET levels, inhibited MET ubiquitination, and consequently restored MET protein levels. Moreover, in NSCLC clinical specimens harboring activating EGFR mutations, more than 30% of patients expressed high levels of HGF. Our findings raised the possibility that patients with NSCLC with EGFR mutations who express high levels of HGF may benefit from onartuzumab and erlotinib combination therapy, and that HGF can be a novel biomarker for selecting such patients. Mol Cancer Ther; 14(2); 533–41. ©2014 AACR.
Clinical and Cellular Roles for TDP1 and TOP1 in Modulating Colorectal Cancer Response to Irinotecan
Authors: Meisenberg Cornelia , Gilbert Duncan C. , Chalmers Anthony , Haley Vikki , Gollins Simon , Ward Simon E. , El-Khamisy Sherif F. 
Published: December 2014

Abstract
Colorectal cancer is the third most common cancer in the world. Despite surgery, up to 50% of patients relapse with incurable disease. First-line chemotherapy uses the topoisomerase 1 (TOP1) poison irinotecan, which triggers cell death by trapping TOP1 on DNA. The removal of TOP1 peptide from TOP1–DNA breaks is conducted by tyrosyl-DNA phosphodiesterase 1 (TDP1). Despite putative roles for TDP1 and TOP1 in colorectal cancer, their role in cellular and clinical responses to TOP1-targeting therapies remains unclear. Here, we show varying expression levels of TOP1 and TDP1 polypeptides in multiple colorectal cancer cell lines and in clinical colorectal cancer samples. TDP1 overexpression or TOP1 depletion is protective. Conversely, TDP1 depletion increases DNA-strand breakage and hypersensitivity to irinotecan in a TOP1-dependent manner, presenting a potential therapeutic opportunity in colorectal cancer. TDP1 protein levels correlate well with mRNA and with TDP1 catalytic activity. However, no correlation is observed between inherent TDP1 or TOP1 levels alone and irinotecan sensitivity, pointing at their limited utility as predictive biomarkers in colorectal cancer. These findings establish TDP1 as a potential therapeutic target for the treatment of colorectal cancer and question the validity of TOP1 or TDP1 on their own as predictive biomarkers for irinotecan response. Mol Cancer Ther; 14(2); 575–85. ©2014 AACR.
Epitope mapping via selection of anti-FVIII antibody-specific phagepresented peptide ligands that mimic the antibody binding sites
Authors: Kahle Joerg , Orlowski Aleksander , Stichel Diana , Becker-Peters Karin , Kabiri Ali , Healey John F. , Brettschneider Kerstin , Naumann Anja , Scherger Anna Katharina , Lollar Pete , Schwabe Dirk , Königs Christoph 
Published: December 2014

SummaryThe most serious complication in today’s treatment of congenital haemophilia A is the development of neutralising antibodies (inhibitors) against factor VIII (FVIII). Although FVIII inhibitors can be eliminated by immune tolerance induction (ITI) based on repeated administration of high doses of FVIII, 20–30% of patients fail to become tolerant. Persistence of FVIII inhibitors is associated with increased morbidity and mortality. Data from recent studies provide evidence for a potential association between ITI outcome and epitope specificity of FVIII inhibitors. Nevertheless the determination of epitopes and their clinical relevance has not yet been established. In this study a general strategy for the identification of anti-FVIII antibody epitopes in haemophilia A patient plasma was to be demonstrated. Phage-displayed peptide libraries were screened against anti-FVIII antibodies to isolate specific peptides. Peptide specificity was confirmed by FVIII-sensitive ELISA binding. Peptide residues essential for antibody binding were identified by mutational analysis and epitopes were predicted via FVIII homology search. The proposed mapping strategy was validated for the monoclonal murine antibody (mAb) 2–76. Binding studies with FVIII variants confirmed the location of the predicted epitope at the level of individual amino acids. In addition, anti-FVIII antibody-specific peptide ligands were selected for 10 haemophilia A patients with FVIII inhibitors. Detailed epitope mapping for three of them showed binding sites on the A2, A3 and C2 domains. Precise epitope mapping of anti-FVIII antibodies using antibody-specific peptide ligands can be a useful approach to identify antigenic sites on FVIII.
Testing of a Cell-Integrated Semi-Lagrangian Semi-Implicit Nonhydrostatic Atmospheric Solver (CSLAM-NH) with Idealized Orography
Authors: Wong May , Skamarock William C. , Lauritzen Peter H. , Klemp Joseph B. , Stull Roland B. 
Published: December 2014

Abstract
A recently developed cell-integrated semi-Lagrangian (CISL) semi-implicit nonhydrostatic atmospheric solver that uses the conservative semi-Lagrangian multitracer (CSLAM) transport scheme is extended to include orographic influences. With the introduction of a new semi-implicit CISL discretization of the continuity equation, the nonhydrostatic solver, called CSLAM-NH, has been shown to ensure inherently conservative and numerically consistent transport of air mass and other scalar variables, such as moisture and passive tracers. The extended CSLAM-NH presented here includes two main modifications: transformation of the equation set to a terrain-following height coordinate to incorporate orography and an iterative centered-implicit time-stepping scheme to enhance the stability of the scheme associated with gravity wave propagation at large time steps. CSLAM-NH is tested for a suite of idealized 2D flows, including linear mountain waves (dry), a downslope windstorm (dry), and orographic cloud formation.
Assessment of predicted versus measured thermal comfort and optimal comfort ranges in the outdoor environment in the temperate climate of Glasgow, UK
Authors: Oertel Annika , Emmanuel Rohinton , Drach Patricia 
Published: December 2014

In a warming world, the risk of overheating is significant in temperate climate areas such as Glasgow, UK where adaptation to overheating is low. An easy-to-use thermal comfort evaluation is therefore a necessary first step towards developing effective coping mechanisms. In this study, we explore the effectiveness of Predicted Mean Vote, Predicted Percentage of Dissatisfied and Physiologically Equivalent Temperature, together with air temperature in mimicking actual thermal sensation votes of street users obtained in 2011 in Glasgow City Centre. The Predicted Mean Vote/Predicted Percentage of Dissatisfied indices developed for controlled indoors show a surprising similarity to actual thermal sensation votes derived from outdoor surveys, than the Physiologically Equivalent Temperature developed specifically for the outdoors. The method of calculation of mean radiant temperature is the key to improved performance of Physiologically Equivalent Temperature, with fish-eye lens photographs improving its performance. The results also show air temperature alone has nearly equal predictive power of the actual thermal sensation. A preliminary comfort range for Glasgow is also derived and its limitations are explored. Practical application: The strong relation between thermal sensation votes and air temperature (Ta) enables future thermal comfort studies to predict the thermal comfort using easy-to-access Ta only. A current thermal comfort study in Glasgow aiming at developing a link between urban morphology and Ta is already using this strong relation to predict outdoor thermal comfort in the city centre. This helps to establish a correlation between these three factors.
Thromboembolic Events in Malignant Pleural Mesothelioma
Authors: Koksal Deniz , Safak Ozge , Ozcan Aysenaz , Agackiran Yetkin , Erturk Hakan , Findik Gokturk 
Published: December 2014

Aim: Malignant pleural mesothelioma (MPM) increases the risk of thromboembolic events (TEEs). In this retrospective study, we aimed to determine the rate of TEEs in MPM and investigate its relationship with the presence of thrombocytosis, the disease stage, and the tumor histopathology. Methods: The study included 178 patients who were histopathologically diagnosed as MPM between the years January 2008 and June 2014. Results: The mean age was 58.7 ± 11.8 years, and the median follow-up time was 8 months. Seventy-one patients (39.9%) had thrombocytosis (>350 × 103/mL). In total, 14 (7.9%) TEEs were identified: 6 (3.4%) pulmonary thromboembolism, 6 (3.4%) deep venous thrombosis, and 2 (1.1%) myocardial infarctions. Although 5 (2.8%) of the TEEs preceded the diagnosis of MPM, 1 (0.6%) occurred simultaneously with the diagnosis of MPM and 8 (4.5%) followed the diagnosis of MPM. Thromboembolic event rates were not statistically different based on the presence of thrombocytosis ( P = .51), disease stage ( P = .14), and histopathology ( P = .38). Conclusion: The rate of TEEs was 7.9%. Presence of thrombocytosis, disease stage, and histopathology did not affect the incidence of TEEs.
Cancer progression by breast tumors with Pit-1-overexpression is blocked by inhibition of metalloproteinase (MMP)-13
Authors: Sendon-Lago Juan , Seoane Samuel , Eiro Noemi , Bermudez Maria A , Macia Manuel , Garcia-Caballero Tomas , Vizoso Francisco J , Perez-Fernandez Roman 
Published: December 2014

Abstract
Introduction
The POU class 1 homeobox 1 transcription factor (POU1F1, also known as Pit-1) is expressed in the mammary gland and its overexpression induces profound phenotypic changes in proteins involved in cell proliferation, apoptosis, and invasion. Patients with breast cancer and elevated expression of Pit-1 show a positive correlation with the occurrence of distant metastasis. In this study we evaluate the relationship between Pit-1 and two collagenases: matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-13 (MMP-13), which have been related to metastasis in breast cancer.

Methods
We began by transfecting the MCF-7 and MDA-MB-231 human breast adenocarcinoma cell lines with the Pit-1 overexpression vector (pRSV-hPit-1). Afterward, the mRNA, protein, and transcriptional regulation of both MMP-1 and MMP-13 were evaluated by real-time PCR, Western blot, chromatin immunoprecipitation (ChIP), and luciferase reporter assays. We also evaluated Pit-1 overexpression with MMP-1 and MMP-13 knockdown in a severe combined immunodeficiency (SCID) mouse tumor xenograft model. Finally, by immunohistochemistry we correlated Pit-1 with MMP-1 and MMP-13 protein expression in 110 human breast tumors samples.

Results
Our data show that Pit-1 increases mRNA and protein of both MMP-1 and MMP-13 through direct transcriptional regulation. In SCID mice, knockdown of MMP-13 completely blocked lung metastasis in Pit-1-overexpressing MCF-7 cells injected into the mammary fat pad. In breast cancer patients, expression of Pit-1 was found to be positively correlated with the presence of both MMP-1 and MMP-13.

Conclusions
Our data indicates that Pit-1 regulates MMP-1 and MMP-13, and that inhibition of MMP-13 blocked invasiveness to lung in Pit-1-overexpressed breast cancer cells.
FBPA PET in boron neutron capture therapy for cancer: prediction of 10B concentration in the tumor and normal tissue in a rat xenograft model
Authors: Hanaoka Kohei , Watabe Tadashi , Naka Sadahiro , Kanai Yasukazu , Ikeda Hayato , Horitsugi Genki , Kato Hiroki , Isohashi Kayako , Shimosegawa Eku , Hatazawa Jun 
Published: December 2014

Abstract

Background
Boron neutron capture therapy (BNCT) is a molecular radiation treatment based on the 10B (n, α) 7Li nuclear reaction in cancer cells, in which delivery of 10B by 4-borono-phenylalanine conjugated with fructose (BPA-fr) to the cancer cells is of critical importance. The PET tracer 4-borono-2-18 F-fluoro-phenylalanine (FBPA) has been used to predict the accumulation of BPA-fr before BNCT. However, because of the difference in chemical structure between BPA-fr and FBPA and the difference in the dose administered between BPA-fr (therapeutic dose) and FBPA (tracer dose), the predictive value of FBPA PET for BPA-fr accumulation in the tumor and normal tissues is not yet clearly proven. We conducted this study to validate FBPA PET as a useful test to predict the accumulation of BPA-fr in the tumor and normal tissues before BNCT.

Methods
RGC-6 rat glioma cells (1.9 × 107) were implanted subcutaneously in seven male F344 rats. On day 20 after the tumor implantation, dynamic PET scan was performed on four rats after injection of FBPA for 1 h. Whole-body PET/CT was performed 1 h after intravenous injection of the FBPA solution (30.5 ± 0.7 MBq, 1.69 ± 1.21 mg/kg). PET accumulation of FBPA in the tumor tissue and various normal tissues was estimated as a percentage of the injected dose per gram (%ID/g). One hour after the PET/CT scan, BPA-fructose (167.32 ± 18.65 mg/kg) was injected intravenously, and the rats were dissected 1 h after the BPA-fr injection. The absolute concentration of 10B in the autopsied tissues and blood was measured by inductively coupled plasma optical emission spectrometry (ICP-OES).

Results
The highest absolute concentration of 10B determined by ICP-OES was found in the kidney (4.34 ± 0.84 %ID/g), followed by the pancreas (2.73 ± 0.63 %ID/g), and the tumor (1.44 ± 0.44 %ID/g). A significant positive correlation was found between the accumulation levels of BPA-fr and FBPA (r = 0.91, p < 0.05).

Conclusions
FBPA PET can reliably predict accumulation of BPA-fr in the tumor as well as normal tissues.
Solvability for second-order nonlocal boundary value problems with "Equation missing"
Authors: Jeong Jeongmi , Kim Chan-Gyun , Lee Eun Kyoung 
Published: December 2014

Abstract
The existence of at least one solution to the second-order nonlocal boundary value problems on the real line is investigated by using an extension of Mawhin’s continuation theorem.

MSC: 34B10, 34B40, 34B15.
Hypoxia Inhibits Cavin-1 and Cavin-2 Expression and Down-Regulates Caveolae in Adipocytes
Authors: Regazzetti Claire , Dumas Karine , Lacas-Gervais Sandra , Pastor Faustine , Peraldi Pascal , Bonnafous Stéphanie , Dugail Isabelle , Le Lay Soazig , Valet Philippe , Le Marchand-Brustel Yannick , Tran Albert , Gual Philippe , Tanti Jean-François , Cormont Mireille , Giorgetti-Peraldi Sophie 
Published: December 2014

AbstractDuring obesity, a hypoxic state develops within the adipose tissue, resulting in insulin resistance. To understand the underlying mechanism, we analyzed the involvement of caveolae because they play a crucial role in the activation of insulin receptors. In the present study, we demonstrate that in 3T3-L1 adipocytes, hypoxia induces the disappearance of caveolae and inhibits the expression of Cavin-1 and Cavin-2, two proteins necessary for the formation of caveolae. In mice, hypoxia induced by the ligature of the spermatic artery results in the decrease of cavin-1 and cavin-2 expression in the epididymal adipose tissue. Down-regulation of the expression of cavins in response to hypoxia is dependent on hypoxia-inducible factor-1. Indeed, the inhibition of hypoxia-inducible factor-1 restores the expression of cavins and caveolae formation. Expression of cavins regulates insulin signaling because the silencing of cavin-1 and cavin-2 impairs insulin signaling pathway. In human, cavin-1 and cavin-2 are decreased in the sc adipose tissue of obese diabetic patients compared with lean subjects. Moreover, the expression of cavin-2 correlates negatively with the homeostatic model assessment index of insulin resistance and glycated hemoglobin level. In conclusion, we propose a new mechanism in which hypoxia inhibits cavin-1 and cavin-2 expression, resulting in the disappearance of caveolae. This leads to the inhibition of insulin signaling and the establishment of insulin resistance.
The Yerkes-Dodson law and appropriate stimuli for conditioned taste aversion in Lymnaea
Authors: Ito Etsuro , Yamagishi Miki , Takigami Satoshi , Sakakibara Manabu , Fujito Yutaka , Lukowiak Ken 
Published: December 2014

Abstract
The pond snail Lymnaea stagnalis can learn conditioned taste aversion and then consolidate it into long-term memory (LTM). A high voltage electric shock was used as the unconditioned stimulus (US), whereas we previously used KCl. We varied both the strength of the conditioned stimulus (CS) and US to determine if the so-called Yerkes-Dodson law prevailed. This is an empirical relationship between the state of arousal and LTM formation, showing that there is an optimal level of arousal leading to memory formation. However, too little or too much arousal results in poorer LTM. We found here that the most appropriate stimuli to use in taste aversion training in Lymnaea were a 10 mmol l-1 sucrose solution as the CS and a 3-s electric shock as the US.
Field research of a wedge-shaped core on the models of the strip foundations with variable geometric shape
Authors: Архипов Дмитрий , Arkhipov Dmitriy , Евтушенко Сергей , Evtushenko Sergey , Скибин Геннадий , Skibin Gennadiy 
Published: December 2014

Many authors noted in the field research on the models
of rigid foundations that a compacted wedge-shaped core of soil is
formed with the destruction of the bases, which is a natural extension
of the foundation.
In the research of the strip foundation model with variable geometric
shape of the foundation base, a compaction soil area of spherical
shape with a diameter close to the width of the foundation model is
found on a sand base.
A wedge-shaped core, along the edges of which there has been a
shift in mass of the base when achieving the ultimate loading, has
been noted in a compaction soil area.
The solid part of the foundation base is the compacted wedge-shaped
core base, the height of the wedge-shaped core being commensurate
with the length of the elements forming the foundation.
Identified geometric parameters of compacted core under the foundation
base of strip foundation with geometrically variable shape
can be used in determining the ultimate bearing capacity of soil of
the base for such foundations.
Deciding for Others Reduces Loss Aversion
Authors: Andersson Ola , Holm Håkan J. , Tyran Jean-Robert , Wengström Erik 
Published: December 2014

We study risk taking on behalf of others, both when choices involve losses and when they do not. A large-scale incentivized experiment with subjects randomly drawn from the Danish population is conducted. We find that deciding for others reduces loss aversion. When choosing between risky prospects for which losses are ruled out by design, subjects make the same choices for themselves as for others. In contrast, when losses are possible, we find that the two types of choices differ. In particular, we find that subjects who make choices for themselves take less risk than those who decide for others when losses loom. This finding is consistent with an interpretation of loss aversion as a bias in decision making driven by emotions and that these emotions are reduced when making decisions for others. This paper was accepted by Uri Gneezy, behavioral economics.
A symmetry result for strictly convex domains
Authors: Ramm Alexander G. 
Published: December 2014

Abstract
Let

D
⊂

ℝ
2

${D\subset \mathbb {R}^2}$

be a strictly convex domain with C
2-smooth boundary.
Assume that

∫
D

e

i
x

y
n

d
x
d
y
=
0

${\int _De^{ix}y^n\,dxdy=0}$

for all sufficiently large n.
In this paper, we will prove that D is a disc.
Crystal structure of poly[aqua(1,2-bis(4-pyridyl)ethane-κ2N:N’)(4-nitro- 1,2-benzenedicarboxylate-κ3O,O’:O’’)cobalt(II)], C20H17CoN3O7
Authors: Yin Wei-Dong , Li Gui-Lian 
Published: December 2014

Abstract C20H17CoN3O7, monoclinic, C2/c (no. 15), a = 27.441(6) Å, b = 7.569(2) Å, c = 19.961(5) Å, β = 111.521(2)°, V = 3856.6 Å3, Z = 8, Rgt(F) = 0.0477, wRref(F2) = 0.1115, T = 296 K.