bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathological adaptive responses of Schwann cells to endoplasmic reticulum stress in bortezomib‐induced peripheral neuropathy
Authors: Shin Yoon Kyung , Jang So Young , Lee Hyun Kyoung , Jung Junyang , Suh Duk Joon , Seo Su‐Yeong , Park Hwan Tae 
Published: September 2010

AbstractBortezomib, a proteasome inhibitor, has been considered as a promising anticancer drug in the treatment of recurrent multiple myeloma and some solid tumors. The bortezomib‐induced peripheral neuropathy (BIPN) is a prominent cause of dose‐limiting toxicities after bortezomib treatment. In this study, we found that BIPN in a mouse model is characterized by acute but transient endoplasmic reticulum (ER) damages to Schwann cells. These damaged Schwann cells exhibit abnormal outcomes from healing processes such as the myelination of Remak bundles. A morphometric analysis of polymyelinated Remak bundles revealed that the pathological myelination was not related to the axonal parameters that regulate the normal myelination process during development. In addition, demyelinating macrophages were focally infiltrated within endoneurium of the sciatic nerve. To identify the mechanism underlying these pathologies, we applied a gene microarray analysis to bortezomib‐treated primary Schwann cells and verified the changes of several gene expression in bortezomib‐treated sciatic nerves. The analysis showed that bortezomib‐induced ER stress was accompanied by the activation of several protective molecular chaperones and the down‐regulation of myelin gene expression. ER stress inducers such as thapsigargin and bredelfin A also suppressed the mRNA expression of myelin gene P0 at transcriptional levels. In addition, the expression of chemokines such as the macrophage chemoattractants Ccl3 and Cxcl2 was significantly increased in Schwann cells in response to bortezomib and ER stress inducers. Taken together, these observations suggest that the pathological adaptive responses of Schwann cells to bortezomib‐induced ER stress may, in part, participate in the development of BIPN. © 2010 Wiley‐Liss, Inc.
Numerically modelling groundwater in an arid area with ANN‐generated dynamic boundary conditions
Authors: Huo Zailin , Feng Shaoyuan , Kang Shaozhong , Mao Xiaomin , Wang Fengxin 
Published: September 2010

AbstractGroundwater is sensitive to the climate change and agricultural activities in arid and semi‐arid areas. Over the past several decades, human activities, such as groundwater extraction for irrigation, have resulted in aquifer overdraft and disrupted the natural equilibrium in these areas. Regional groundwater simulation is important to determine appropriate groundwater management policies, and numerical simulation has become the most popular method. However, most groundwater models were developed with static boundary conditions. In this research, the Minqin oasis, an arid region located in northwest China, was selected as the study area. An artificial neural network (ANN) was developed to simulate effects of weather conditions, agricultural activities and surface water on groundwater level in a dynamic boundary of the domain. Subsequently, a groundwater numerical model, named ANN‐FEFLOW model, was developed, with a dynamic boundary condition defined by the ANN model. The verifying results showed that the model has higher precision, with a root mean square error (RMSE) of 0·71 m, relative error (RE) of 17·96% and R2 of 0·84 relative to the great groundwater change. Furthermore, the groundwater model has higher precision than the conventional groundwater model with static boundary condition, particularly in the area near the dynamic boundary. This study demonstrated that dynamic boundaries can improve the precision of the regional groundwater model in an arid area and that ANN can provide higher accuracy prediction capability for groundwater levels with dynamic boundary. Copyright © 2010 John Wiley & Sons, Ltd.
MT119, a new planar‐structured compound, targets the colchicine site of tubulin arresting mitosis and inhibiting tumor cell proliferation
Authors: Zhang Zhixiang , Meng Tao , Yang Na , Wang Wei , Xiong Bing , Chen Yi , Ma Lanping , Shen Jingkang , Miao Ze‐Hong , Ding Jian 
Published: September 2010

AbstractMicrotubule‐targeted drugs are now indispensable for the therapy of various cancer types worldwide. In this article, we report MT119 [6‐[2‐(4‐methoxyphenyl) ‐ethyl]‐9‐[(pyridine‐3‐ylmethyl)amino]pyrido[2′,1′:2,3]imida‐zo[4,5‐c]isoquinolin‐5(6H)‐one] as a new microtubule‐targeted agent. MT119 inhibited tubulin polymerization significantly both in tumor cells and in cell‐free systems, which was followed by the disruption of mitotic spindle assembly. Surface plasmon resonance‐based analyses showed that MT119 bound to purified tubulin directly, with theKDvalue of 10.6 μM. The binding of MT119 in turn caused tubulin conformational changes as evidenced by the quenched tryptophan fluorescence, the reduction of the bis‐ANS reactivity and the decreased DTNB‐sulfhydryl reaction rate. Competitive binding assays further revealed that MT119 bound to tubulin at its colchicine site. Consequently, by inhibiting tubulin polymerization, MT119 arrested different tumor cells at mitotic phase, which contributed to its potent antitumor activityin vitro.MT119 was also similarly cytotoxic to vincristine‐, adriamycin‐ or mitoxantrone‐resistant cancer cells and to their corresponding parental cells. Together, these data indicate that MT119 represents a new class of colchicine‐site‐targeted inhibitors against tubulin polymerization, which might be a promising starting point for future cancer therapeutics.
A nation‐wide study comparing sporadic and familial adenomatous polyposis‐related desmoid‐type fibromatoses
Authors: Nieuwenhuis Marry H. , Casparie Mariel , Mathus‐Vliegen Lisbeth M.H. , Dekkers Olaf M. , Hogendoorn Pancras C.W. , Vasen Hans F.A. 
Published: September 2010

AbstractDesmoid‐type fibromatoses are neoplasms of fibroblastic origin, occurring sporadically or associated with familial adenomatous polyposis (FAP) coli. By comparing sporadic and FAP‐associated desmoid‐type fibromatoses, we tried to identify clinical characteristics, which may indicate FAP. Histopathology data of all Dutch patients with desmoid‐type fibromatoses diagnosed between 1999 and 2009 were retrieved from PALGA, the nation‐wide network and registry of histopathology in the Netherlands. For calculation of incidence rates, person‐years from the general matched population were used. Based on polyp counts in pathological records, the cohort was divided into a FAP group and a non‐FAP group. Patient‐ and tumor characteristics were compared between the two groups. A total number of 519 patients older than 10 years with a confirmed diagnosis of desmoid‐type fibromatoses were included. Thirty‐nine (7.5%) desmoid patients were documented of having FAP. The incidences of sporadic and FAP‐related desmoid‐type fibromatoses were 3.42 and 2,784 per million person‐years, respectively. The majority of FAP patients developed desmoid‐type fibromatoses after the diagnosis of FAP. Having FAP was associated with male gender [odds ratio (OR) 2.0, p = 0.034], desmoid diagnosis at an earlier age (mean 36 vs. 42 years, p = 0.031), and desmoid localization intra‐abdominally (OR 18.9, p ≤ 0.001) or in the abdominal wall (OR 4.8, p ≤ 0.001), compared to extra‐abdominal desmoid localization. In conclusion, patients with desmoid‐type fibromatoses are at risk of underlying FAP. Especially cases with desmoid localization intra‐abdominal or in the abdominal wall, and all patients younger than 60 years, have a substantial increased risk and should be referred for colonoscopy.
CXCR4 peptide antagonist inhibits primary breast tumor growth, metastasis and enhances the efficacy of anti‐VEGF treatment or docetaxel in a transgenic mouse model
Authors: Hassan Saima , Buchanan Marguerite , Jahan Kaushar , Aguilar‐Mahecha Adriana , Gaboury Louis , Muller William J. , Alsawafi Yaqoob , Mourskaia Anna A. , Siegel Peter M. , Salvucci Ombretta , Basik Mark 
Published: September 2010

AbstractCXCR4 is a chemokine receptor implicated in the homing of cancer cells to target metastatic organs, which overexpress its ligand, stromal cell‐derived factor (SDF)‐1. To determine the efficacy of targeting CXCR4 on primary tumor growth and metastasis, we used a peptide inhibitor of CXCR4, CTCE‐9908, that was administered in a clinically relevant approach using a transgenic breast cancer mouse model. We first performed a dosing experiment of CTCE‐9908 in the PyMT mouse model, testing 25, 50 and 100 mg/kg versus the scrambled peptide in groups of 8–16 mice. We then combined CTCE‐9908 with docetaxel or DC101 (an anti‐VEGFR2 monoclonal antibody). We found that increasing doses of CTCE‐9908 alone slowed the rate of tumor growth, with a 45% inhibition of primary tumor growth at 3.5 weeks of treatment with 50 mg/kg of CTCE‐9908 (p = 0.005). Expression levels of VEGF were also found to be reduced by 42% with CTCE‐9908 (p = 0.01). In combination with docetaxel, CTCE‐9908 administration decreased tumor volume by 38% (p = 0.02), an effect that was greater than that observed with docetaxel alone. In combination with DC101, CTCE‐9908 also demonstrated an enhanced effect compared to DC101 alone, with a 37% decrease in primary tumor volume (p = 0.01) and a 75% reduction in distant metastasis (p = 0.009). In combination with docetaxel or an anti‐angiogenic agent, the anti‐tumor and anti‐metastatic effects of CTCE‐9908 were markedly enhanced, suggesting potentially new effective combinatorial therapeutic strategies in the treatment of breast cancer, which include targeting the SDF‐1/CXCR4 ligand/receptor pair.
Increased efficacy of doxorubicin delivered in multifunctional microparticles for mesothelioma therapy
Authors: Hillegass Jedd M. , Blumen Steven R. , Cheng Kai , MacPherson Maximilian B. , Alexeeva Vlada , Lathrop Sherrill A. , Beuschel Stacie L. , Steinbacher Jeremy L. , Butnor Kelly J. , Ramos‐Niño Maria E. , Shukla Arti , James Ted A. , Weiss Daniel J. , Taatjes Douglas J. , Pass Harvey I. , Carbone Michele , Landry Christopher C. , Mossman Brooke T. 
Published: September 2010

AbstractNew and effective treatment strategies are desperately needed for malignant mesothelioma (MM), an aggressive cancer with a poor prognosis. We have shown previously that acid‐prepared mesoporous microspheres (APMS) are nontoxic after intrapleural or intraperitoneal (IP) administration to rodents. The purpose here was to evaluate the utility of APMS in delivering chemotherapeutic drugs to human MM cells in vitro and in two mouse xenograft models of MM. Uptake and release of doxorubicin (DOX) alone or loaded in APMS (APMS‐DOX) were evaluated in MM cells. MM cell death and gene expression linked to DNA damage/repair were also measured in vitro. In two severe combined immunodeficient mouse xenograft models, mice received saline, APMS, DOX or APMS‐DOX injected directly into subcutaneous (SC) MM tumors or injected IP after development of human MMs peritoneally. Other mice received DOX intravenously (IV) via tail vein injections. In comparison to DOX alone, APMS‐DOX enhanced intracellular uptake of DOX, MM death and expression of GADD34 and TP73. In the SC MM model, 3× weekly SC injections of APMS‐DOX or DOX alone significantly inhibited tumor volumes, and systemic DOX administration was lethal. In mice developing IP MMs, significant (p < 0.05) inhibition of mesenteric tumor numbers, weight and volume was achieved using IP administration of APMS‐DOX at one‐third the DOX concentration required after IP injections of DOX alone. These results suggest APMS are efficacious for the localized delivery of lower effective DOX concentrations in MM and represent a novel means of treating intracavitary tumors.
Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia: Testing a device as an adjunct to colposcopy
Authors: Cantor Scott B. , Yamal Jose‐Miguel , Guillaud Martial , Cox Dennis D. , Atkinson E. Neely , Benedet John L. , Miller Dianne , Ehlen Thomas , Matisic Jasenka , van Niekerk Dirk , Bertrand Monique , Milbourne Andrea , Rhodes Helen , Malpica Anais , Staerkel Gregg , Nader‐Eftekhari Shahla , Adler‐Storthz Karen , Scheurer Michael E. , Basen‐Engquist Karen , Shinn Eileen , West Loyd A. , Vlastos Anne‐Therese , Tao Xia , Beck J. Robert , MacAulay Calum , Follen Michele 
Published: September 2010

AbstractTesting emerging technologies involves the evaluation of biologic plausibility, technical efficacy, clinical effectiveness, patient satisfaction, and cost‐effectiveness. The objective of this study was to select an effective classification algorithm for optical spectroscopy as an adjunct to colposcopy and obtain preliminary estimates of its accuracy for the detection of CIN 2 or worse. We recruited 1,000 patients from screening and prevention clinics and 850 patients from colposcopy clinics at two comprehensive cancer centers and a community hospital. Optical spectroscopy was performed, and 4,864 biopsies were obtained from the sites measured, including abnormal and normal colposcopic areas. The gold standard was the histologic report of biopsies, read 2 to 3 times by histopathologists blinded to the cytologic, histopathologic, and spectroscopic results. We calculated sensitivities, specificities, receiver operating characteristic (ROC) curves, and areas under the ROC curves. We identified a cutpoint for an algorithm based on optical spectroscopy that yielded an estimated sensitivity of 1.00 [95% confidence interval (CI) = 0.92–1.00] and an estimated specificity of 0.71 [95% CI = 0.62–0.79] in a combined screening and diagnostic population. The positive and negative predictive values were 0.58 and 1.00, respectively. The area under the ROC curve was 0.85 (95% CI = 0.81–0.89). The per‐patient and per‐site performance were similar in the diagnostic and poorer in the screening settings. Like colposcopy, the device performs best in a diagnostic population. Alternative statistical approaches demonstrate that the analysis is robust and that spectroscopy works as well as or slightly better than colposcopy for the detection of CIN 2 to cancer.
Differential regulation by fucoidan of IFN‐γ‐induced NO production in glial cells and macrophages
Authors: Do Hang , Kang Nam‐Sung , Pyo Suhkneung , Billiar Timothy R. , Sohn Eun‐Hwa 
Published: September 2010

AbstractFucoidan has shown numerous biological actions; however, the molecular bases of these actions have being issued. We examined the effect of fucoidan on NO production induced by IFN‐γ and the molecular mechanisms underlying these effects in two types of cells including glia (C6, BV‐2) and macrophages (RAW264.7, peritoneal primary cells). Fucoidan affected IFN‐γ‐induced NO and/or iNOS expression both in macrophages and glial cells but in a contrast way. Our data showed that in C6 glioma cells both JAK/STAT and p38 signaling positively regulated IFN‐γ‐induced iNOS, which were inhibited by fucoidan. In contrast, in RAW264.7 cells JAK/STAT is a positive regulator whereas p38 is a negative regulator of NO/iNOS production. In RAW264.7 cells, fucoidan enhanced p38 activation and induced TNF‐α production. We also confirmed the dual regulation of p38 in BV‐2 microglia and primary peritoneal macrophages. From these results, we suggest that fucoidan affects not only IFN‐γ‐induced NO/iNOS production differently in brain and peritoneal macrophages due to the different roles of p38 but the effects on TNF‐α production in the two cell types. These novel observations including selective and cell‐type specific effects of fucoidan on IFN‐γ‐mediated signaling and iNOS expression raise the possibility that it alters the sensitivity of cells to the p38 activation. J. Cell. Biochem. 111: 1337–1345, 2010. © 2010 Wiley‐Liss, Inc.
Prohibitin is a cholesterol‐sensitive regulator of cell cycle transit
Authors: Dong Pei , Flores Jessica , Pelton Kristine , Solomon Keith R. 
Published: September 2010

AbstractCholesterol is essential in establishing most functional animal cell membranes; cells cannot grow or proliferate in the absence of sufficient cholesterol. Consequently, almost every cell, tissue, and animal tightly regulates cholesterol homeostasis, including complex mechanisms of synthesis, transport, uptake, and disposition of cholesterol molecules. We hypothesize that cellular recognition of cholesterol insufficiency causes cell cycle arrest in order to avoid a catastrophic failure in membrane synthesis. Here, we demonstrate using unbiased proteomics and standard biochemistry that cholesterol insufficiency causes upregulation of prohibitin, an inhibitor of cell cycle progression, through activation of a cholesterol‐responsive promoter element. We also demonstrate that prohibitin protects cells from apoptosis caused by cholesterol insufficiency. This is the first study tying cholesterol homeostasis to a specific cell cycle regulator that inhibits apoptosis. J. Cell. Biochem. 111: 1367–1374, 2010. © 2010 Wiley‐Liss, Inc.
Expression of homeobox genes in oral squamous cell carcinoma cell lines treated with all‐trans retinoic acid
Authors: Acquafreda Thais , Nunes Fabio Daumas , Soprano Dianne Robert , Soprano Kenneth J. 
Published: September 2010

AbstractOral squamous cell carcinoma (OSCC) may arise from potentially malignant oral lesions. All‐trans retinoic acid (atRA), which plays a role in cell growth and differentiation, has been studied as a possible chemotherapeutic agent in the prevention of this progression. While the mechanism by which atRA suppresses cell growth has not been completely elucidated, it is known that homeobox genes are atRA targets. To determine if these genes are involved in the atRA‐mediated OSCC growth inhibition, PCR array was performed to evaluate the expression of 84 homeobox genes in atRA‐sensitive SCC‐25 cells compared to atRA‐resistant SCC‐9 cells following 7 days with atRA treatment. Results showed that the expression of 8 homeobox genes was downregulated and expression of 4 was upregulated in SCC‐25 cells but not in SCC‐9 cells. Gene expression levels were confirmed for seven of these genes by RT‐qPCR. Expression of three genes that showed threefold downregulation was evaluated in SCC‐25 cells treated with atRA for 3, 5, and 7 days. Three different patterns of atRA‐dependent gene expression were observed. ALX1 showed downregulation only on day 7. DLX3 showed reduced expression on day 3 and further reduced on day 7. TLX1 showed downregulation only on days 5 and 7. Clearly the expression of homeobox genes is modulated by atRA in OSCC cell lines. However, the time course of this modulation suggests that these genes are not direct targets of atRA mediating OSCC growth suppression. Instead they appear to act as downstream effectors of atRA signaling. J. Cell. Biochem. 111: 1437–1444, 2010. © 2010 Wiley‐Liss, Inc.
A soft‐cache strategy for pathologist's navigation in virtual microscopy
Authors: Gómez Francisco , Marín Diana , Romero Eduardo 
Published: September 2010

AbstractNavigation through large microscopical images demands special characteristics like flexibility to access image data and progressive recovery or relevant information, i.e., several qualities, magnifications, and random accesses to any desired Window of Interest in the Virtual Slide (VS). Nowadays there exist systems that allow such interaction, but with a certain delay, which is dependent on the application. It has been shown that caching or prefetching policies can speed up interaction with these systems. This article presents an optimal soft‐cache strategy, which improves the navigation times in virtual microscopy. The entire method includes an optimal soft‐cache strategy and a dynamical probabilistic model of a pathologist's navigation. This strategy was implemented as a Client‐Server application, using the JPEG2000‐JPIP standard and evaluated using different navigation patterns, namely, four different pathologists exploring 10 VS, stained with different dyes. The present approach was compared with a conventional soft‐cache method and the cache performance improved, in average, in about a 10%. Microsc. Res. Tech., 2011. © 2010 Wiley‐Liss, Inc.
Gold nanoparticles and quantum dots for bioimaging
Authors: Hutter Eliza , Maysinger Dusica 
Published: September 2010

AbstractNanoparticles are the latest tool acquired by the science of bioimaging, serving primarily as new contrast agents, sensors, or signal enhancing agents in established and developing imaging techniques. This review focuses on the unique properties of two classes of nanoparticles: gold nanoparticles (GNP) and quantum dots, and how these properties are benefiting cellular and in vivo imaging. We discuss the surface plasmon resonance of GNP and its implications for various imaging techniques of biological relevance. Furthermore, the key properties of quantum dots are reviewed, and their use alone or in combination with traditional fluorescent dyes for biological imaging are described. The underlying principles of these techniques are provided, along with some representative examples. Microsc. Res. Tech., 2011. © 2010 Wiley‐Liss, Inc.
Synthesis and crystal structure of novel [1,2,4]oxadiazolo[5,4‐d][1,5]benzothiozepine derivatives containing pyrazole moiety
Authors: Zhou Ying‐Lei , Shen Song‐Wei , Liu Fang‐Ming 
Published: September 2010

Abstract
A series of new substituted‐[1,2,4]oxadiazolo[5,4‐d][1,5]benzothiazepine derivatives containing pyrazole ring 4/4′ was synthesized by substituted‐pyrazolo[1,5]benzothiazepines 2/2′ and substituted‐benzohydroximinoyl chlorides 3 through the 1,3‐dipolar cycloaddition reaction in the presence of Et3N at room temperature, and characterized by MS, IR, 1H NMR and elemental analyses. In addition, the structure of 4′l was determined by X‐ray crystallography. J. Heterocyclic Chem., 2011.
New succinyl‐spaced pyrazoles: Regioselective synthesis of 1,4‐bis[5‐(trichloromethyl)‐1H‐pyrazol‐1‐yl]butane‐1,4‐diones
Authors: Bonacorso Helio G. , Cechinel Cleber A. , Paim Gisele R. , Martins Marcos A. P. , Zanatta Nilo , Flores Alex F. C. 
Published: September 2010

Abstract
The facile and convenient access by a conventional procedure in ethanol as solvent to a new series of succinyl‐spaced pyrazoles including 1,4‐bis[5‐(trichloromethyl)‐5‐hydroxy‐4,5‐dihydro‐1H‐pyrazol‐1‐yl]butane‐1,4‐diones (64–82%) and the respective dehydrated derivatives as 1,4‐bis[5‐(trichloromethyl)‐1H‐pyrazol‐1‐yl]butane‐1,4‐diones in 57–82% yields, from the regioselective cyclocondensation reactions of 4‐substituted 4‐methoxy‐1,1,1‐trichloroalk‐3‐en‐2‐ones with succinic acid dihydrazide, where the 4‐substituents are Me, Ph, 4‐FC6H4, 4‐ClC6H4, 4‐NO2C6H4, 2‐furyl, and 2‐thienyl, is reported. J. Heterocyclic Chem., 2011.
Synthesis and fungicidal activity of novel 1,3‐disubstituted 1H‐diazirine derivatives
Authors: Eliazyan Karine A. , Avetisyan Frunze V. , Jivanshiryan Tamara L. , Pivazyan Vergush A. , Ghazaryan Emma A. , Shahbazyan Lusya V. , Harutyunyan Siranush V. , Yengoyan Aleksandr P. 
Published: September 2010

AbstractA convenient method for synthesis of novel 1‐[pyrimidinyl], 1‐[1,3,5‐triazin‐2‐carbonyl], and 1‐[thiazol‐5‐carbonyl] derivatives of 3‐thioxo‐diaziridine1,3,5, and7from corresponding hydrazides, CS2, and KOH is elaborated. The highest reaction yield was observed when these initial reagents were taken in molar ratio of 1:1.7:2.0, respectively. By alkylation of compounds1,3,5, and7that proceeds exclusively at sulfur atom, the 3‐sulfanyl derivatives of 1‐[pyrimidinyl]‐, 1‐[1,3,5‐triazin‐2‐carbonyl]‐, and 1‐[thiazol‐5‐carbonyl]‐diazirines2,4,6, and8were formed. The structures of synthesized compounds were confirmed by proton and carbon nuclear magnetic resonance (NMR), mass spectra (MS), and elemental analysis. The fungicidal activities of S‐substituted derivatives were studied. Data of preliminary biological tests testify that these compounds can be of interest in search for new fungicides. J. Heterocyclic Chem., (2010).