bluuebunny/crossref_metadata_2025 huggingface dataset:
Site‐specific cytomorphology of disseminated PC‐3 prostate cancer cells visualized in vivo with fluorescent proteins
Authors: Bobek Vladimir , Hoffman Robert M. , Kolostova Katarina
Published: April 2012

Circulating tumor cells (CTC) may reach multiple organ sites. However, CTC seeding and growth in distant organs is not random. Each metastatic site may contain a specific subpopulation of the original metastatic tumor capable of growing at that site. The fluorescent orthotopic prostate cancer model (PC‐3‐GFP) model was used for immunomagnetic capture of CTC. The captured CTC were efficiently cultivated in vitro. PC‐3‐GFP cells were also isolated from various metastatic sites, grown in vitro and examined under fluorescence microscopy. The differential morphology was compared of primary tumor cells, CTC and disseminated (DTC) from multiple metastatic sites, from nude mice with orthotopic PC‐3‐GFP. The cultured captured CTC and DTC from various organs have distinctive morphologies. Distinct cancer cell morphologies were observed at different metastatic sites as well as among CTC. The distinct morphologies were maintained during in vitro culture. The results demonstrate extensive tumor heterogeneity that could account for the widely different behavior of cancer cells in a single tumor. Further hetereogeneity testing would be a big promise for personalizing the cancer treatment in the future. Diagn. Cytopathol. 2013. © 2012 Wiley Periodicals, Inc.
FNA of thyroid granular cell tumor
Authors: Harp Eric , Caraway Nancy P.
Published: April 2012

Granular cell tumor rarely occurs in the thyroid. This case report describes the cytologic features of a granular cell tumor seen in a fine needle aspirate obtained from a 27‐year‐old woman with a gradually enlarging thyroid nodule. The aspirate showed single as well as syncytial clusters of cells with abundant granular cytoplasm. The differential diagnosis in this case included granular cell tumor, Hurthle cell lesion/neoplasm, and a histiocytic reparative process. Immunohistochemical studies, including S‐100 protein and CD68, performed on a cell block preparation were helpful in supporting the diagnosis. Diagn. Cytopathol. 2013;41:825–828. © 2012 Wiley Periodicals, Inc.
Fine needle aspiration cytology in two cases of chondromyxoid fibroma of bone and review of literature
Authors: Sreedharanunni Sreejesh , Gupta Nalini , Rajwanshi Arvind , Bansal Sandeep , Vaiphei Kim
Published: April 2012

We report the cytological features of two cases of chondromyxoid fibroma (CMF) confirmed by histopathology examination. First case was a 40‐year‐old male who presented with a foot swelling, and the second case was a 16‐year‐old male with a lesion at the angle of jaw. A fine needle aspiration cytology (FNAC) was performed in both the cases. In first case, a correct diagnosis of CMF could be offered on FNAC. In the second case, though the cytology diagnosis was a sarcoma considering the cytological, radiological and clinical features, the histopathological examination confirmed the same to be a CMF. The cases are being discussed to highlight the usefulness of FNAC to diagnose these uncommon benign bone lesions and the potential pitfalls in the cytological diagnosis of chondroid lesions. Diagn.
Cytopathol. 2013;41:904–908. © 2012 Wiley Periodicals, Inc.
Erythropoietin and erythropoiesis stimulating agents
Authors: Debeljak Nataša , Sytkowski Arthur J.
Published: April 2012

Erythropoietin (EPO) is the main hormonal regulator of red blood cell production. Recombinant EPO has become the leading drug for treatment of anaemia from a variety of causes; however, it is sometimes misused in sport with the aim of improving performance and endurance. This paper presents an introductory overview of EPO, its receptor, and a variety of recombinant human EPOs/erythropoiesis stimulating agents (ESAs) available on the market (e.g. epoetins and their long acting analogs – darbepoetin alfa and continuous erythropoiesis receptor activator). Recent efforts to improve on EPO's pharmaceutical properties and to develop novel replacement products are also presented. In most cases, these efforts have emphasized a reduction in frequency of injections or complete elimination of intravenous or subcutaneous injections of the hormone (biosimilars, EPO mimetic peptides, fusion proteins, endogenous EPO gene activators and gene doping). Isoelectric focusing (IEF) combined with double immunoblotting can detect the subtle differences in glycosylation/sialylation, enabling differentiation among endogenous and recombinant EPO analogues. This method, using the highly sensitive anti‐EPO monoclonal antibody AE7A5, has been accepted internationally as one of the methods for detecting misuse of ESAs in sport. Copyright © 2012 John Wiley & Sons, Ltd.
Detection of EPO gene doping in blood
Authors: Neuberger Elmo W. I. , Jurkiewicz Magdalena , Moser Dirk A. , Simon Perikles
Published: April 2012

Gene doping – or the abuse of gene therapy – will continue to threaten the sports world. History has shown that progress in medical research is likely to be abused in order to enhance human performance. In this review, we critically discuss the progress and the risks associated with the field of erythropoietin (EPO) gene therapy and its applicability to EPO gene doping. We present typical vector systems that are employed in ex vivo and in vivo gene therapy trials. Due to associated risks, gene doping is not a feasible alternative to conventional EPO or blood doping at this time. Nevertheless, it is well described that about half of the elite athlete population is in principle willing to risk its health to gain a competitive advantage. This includes the use of technologies that lack safety approval. Sophisticated detection approaches are a prerequisite for prevention of unapproved and uncontrolled use of gene therapy technology. In this review, we present current detection approaches for EPO gene doping, with a focus on blood‐based direct and indirect approaches. Gene doping is detectable in principle, and recent DNA‐based detection strategies enable long‐term detection of transgenic DNA (tDNA) following in vivo gene transfer. Copyright © 2012 John Wiley & Sons, Ltd.
Influence of aspect in soil and vegetation water dynamics in dry Mediterranean conditions: functional adjustment of evergreen and semi‐deciduous growth forms
Authors: Gabarrón‐Galeote Miguel Angel , Ruiz‐Sinoga José Damián , Quesada Miguel A.
Published: April 2012

This study was undertaken in a watershed at a dry Spanish Mediterranean location. The effects of the north‐facing and south‐facing aspects on atmospheric parameters, soil water contents (SWCs) and plant water balances were assessed during 18 months including two dry seasons and one wet season. The species studied were the evergreen sclerophyll Quercus suber and the semi‐deciduous shrubs Cistus albidus, Cistus monspeliensis and Lavandula stoechas. Atmospheric parameters were similar in both exposures, but water content of the 30‐cm uppermost soil layers was higher under canopy in the south‐facing slope during the wet season. Water balances of both slopes were different, and this was related to the lower shrub abundance and the vegetation patchiness observed in the south‐facing slope. Autumn plant recovery was faster in the north‐facing hillslope and occurred first in shrubs. During the whole study, Quercus suber displayed a hydrostable strategy maintaining an optimum water balance in both hillslopes. This was not the case of shrubs that avoided drought using a phenological adjustment and were more affected by aspect. Differences between tree and shrub water economies relied mainly on their respective root systems. The faster recovery of shrubs after the first autumn rainfalls allows them to avoid competition with other functional groups for water and nutrients during some days. Leaf‐drying curves distinguished the functional behaviour of the tree and the shrubs because stomatal closure occurred at higher relative water content in the former. The coexistence of both functional strategies ensures an efficient use of water and nutritional resources. Copyright © 2012 John Wiley & Sons, Ltd.
Synthesis of Cerium‐Activated Yttrium Aluminate Based Fine Phosphors by an Aerosol Route
Authors: Mancic Lidija , Lojpur Vesna , Barosso Ignacio , Rabanal Maria Eugenia , Milosevic Olivera
Published: April 2012

Polycrystalline fine powders of yttrium aluminate doped with Ce3+ were synthesised by spray pyrolysis of a polymeric precursor, which was obtained by dissolving the corresponding nitrates in a solution of ethylenediaminetetraacetic acid (EDTA) in ethylene glycol (EG). Aerosol decomposition was performed at 550 °C followed by an additional thermal treatment (900–1100 °C). The yield of either a single yttrium aluminium perovskite (YAP) phase or a single yttrium aluminium garnet (YAG) phase was investigated as a function of the predefined yttrium/aluminium ratio, the cerium doping concentration, the processing temperature, and the thermal‐treatment regime, which included the variation of the heating and cooling rates (dT/dt), the residence time (τ), and the atmosphere. Changes in the composition and structure of the precursor during thermal decomposition were investigated by thermogravimetric and differential thermal analysis (TGA/DTA) and FTIR spectroscopy. The particle morphology and structure were analysed by a combination of scanning electron microscopy and energy‐dispersive X‐ray spectroscopy (SEM/EDS) and by high‐resolution transmission electron microscopy (HR‐TEM). The structural refinement was based on the phase identification performed by X‐ray powder diffraction (XRPD). The emission spectra were recorded within the range 325–800 nm by applying excitation wavelengths of 297 (YAP) and 450 nm (YAG). The employed synthesis conditions assured the formation of spherical, non‐agglomerated particles with well‐developed surfaces and diameters between 200 and 800 nm. For a predefined Y/Al ratio of 1:1, lower processing temperatures combined with longer heat treatments under stationary conditions resulted in a multiphase system, composed of YAP, YAG, and monoclinic yttrium aluminate (YAM) phases. However, a short heat treatment with a high heating rate (200 °C/min) at higher temperatures results in the formation of a kinetically favoured pure YAP hexagonal phase. On the other hand, for a predefined Y/Al ratio of 3:5, the generation of a thermodynamically favoured pure YAG phase has been confirmed, regardless of the applied heat‐treatment conditions. Although incomplete, Ce3+ introduction into the host matrix has been detected by XRPD and luminescence measurements.
Preparation of MgO Nanosheets with Polar (111) Surfaces by Ligand Exchange and Esterification – Synthesis, Structure, and Application as Catalyst Support
Authors: Zhu Kake , Hua Weiming , Deng Wei , Richards Ryan M.
Published: April 2012

Metastable magnesium hydroxymethoxide [Mg(OH)(OCH3)] powder with nanosheet morphology was derived from a direct bottom‐up synthesis using magnesium acetate tetrahydrate as precursor under solvothermal conditions, with benzyl alcohol as structure‐directing agent. The synthesis is driven by esterification of magnesium acetate to the corresponding methyl acetate, namely, ligand exchange and esterification of CH3COO– with CH3O–. A MgO powder featuring a Tasker III type (111) surface as its main exposed surface was produced after decomposition of the as‐prepared Mg(OH)(OCH3) intermediate. X‐ray diffraction (XRD) shows that the as‐formed intermediate is Mg(OH)(OCH3), and methyl acetate is identified in the mother liquor by GC–MS measurements. XRD, SEM, and TEM images also show that the surface of the MgO nanosheets is covered by a Tasker III (111) surface. The vanadia supported on this MgO (111) nanosheet surface is more active than the conventional MgO‐supported system for the oxidative dehydrogenation of ethylbenzene with carbon dioxide, which is attributed to the oxygen‐rich nature and intermediate basicity of the MgO (111) surface.
Protective effect of dietary perilla oil on allergic inflammation in asthmatic mice
Authors: Chang Hui‐Hsiang , Chen Chin‐Shuh , Lin Jin‐Yuarn
Published: April 2012

Perilla oil (PER) is rich in α‐linolenic acid (n‐3 fatty acid). To unravel the effects of dietary PER on allergic asthmatic inflammation, three kinds of dietary oil, including PER, corn oil (COR), and perilla compound oil (50% PER and 50% COR), were used for replacing the oil in an AIN76 feed consumed by ovalbumin (OVA)‐sensitized and challenged mice continuously for 5 wk. T‐helper type 1 lymphocyte (Th1)/T‐helper type 2 lymphocyte (Th2) and pro‐/anti‐inflammatory cytokines secreted by the cells from the airway, the lungs, and the spleen of experimental mice were determined by ELISA. The results showed that dietary PER inhibited interleukin (IL)‐1β and tumor necrosis factor (TNF)‐α secretions by lipopolysaccharide (LPS)‐stimulated lung cells, as well as interferon (IFN)‐γ and IL‐6 secretions by LPS‐stimulated splenocytes. Perilla compound oil increased the secretion ratio of IFN‐γ/IL‐5 (Th1/Th2 cytokines) in LPS‐stimulated bronchoalveolar lavage fluid cells, but decreased the ratio of IL‐6/IL‐10 (pro‐/anti‐inflammatory cytokines) in LPS‐stimulated splenocytes. The present study demonstrated that dietary PER and its compound oil protected the airways, the lungs, and the spleen from allergic inflammation in OVA‐challenged asthmatic mice, suggesting that an appropriate n‐6/n‐3 fatty acid ratio at a ratio of 1:1 or less in dietary oil may be beneficial to improve the Th2‐skewed allergic asthmatic inflammation.

Practical applications:The present study demonstrated that dietary PER and its compound oil protected the airways, the lungs, and the spleen from allergic inflammation in OVA‐challenged asthmatic mice, suggesting that an appropriate n‐6/n‐3 fatty acid ratio at a ratio of 1:1 or less in dietary oil may be beneficial to improve the Th2‐skewed allergic asthmatic inflammation.
Versatile Synthesis of 2‐(Substituted phenyl)‐6,7‐dihydro‐1H‐indol‐4(5H)‐ones from Morita–Baylis–Hillman Acetates of 2‐Oxo‐2‐(substituted phenyl)acetaldehyde
Authors: Batchu Harikrishna , Batra Sanjay
Published: April 2012

A versatile synthesis of 2‐(substituted phenyl)‐6,7‐dihydro‐1H‐indol‐4(5H)‐ones from adducts of the Morita–Baylis–Hillman reaction between 2‐oxo‐2‐(substituted phenyl)acetaldehydes and cyclohex‐2‐enone under mild conditions is described.
On the nature of sexist ambivalence: Profiling ambivalent and univalent sexists
Authors: Sibley Chris G. , Becker Julia C.
Published: April 2012

This study examined the proportion of people who held ambivalent versus univalent sexist attitudes, that is, those who simultaneously endorsed benevolent sexism (BS) and hostile sexism (HS). We examined this by capitalizing on recent innovations in latent class analysis to model latent types of sexists, or response profiles to BS and HS, in a nationally representative New Zealand sample (n = 6450). Our results show, for the first time, that by far, the most common pattern was for people to hold similar levels of BS and HS. Strongly ambivalent sexists, however, constituted only 8%–9% of the population. Most were classified as mild or moderate ambivalent sexists (28% and 44%, respectively). Univalent sexism was exceedingly rare, with between 2% and 5% of people solely endorsing HS but not BS, or BS but not HS. We validated the model by showing theoretically predicted differences across sexist types in demographics (gender, age), ideology (social dominance orientation, right‐wing authoritarianism), and relationship satisfaction. Strongly ambivalent sexists also held the highest levels of gender‐specific system justification, invariant of gender. This provides novel evidence for the premise that strong sexist ambivalence promotes support for and faith in the patriarchical system. Copyright © 2012 John Wiley & Sons, Ltd.
Just ignore or counterattack? On the effects of different strategies for dealing with political attacks
Authors: Carraro Luciana , Castelli Luigi , Breazu Ioana , Campomizzi Giulia , Cerruto Antonella , Mariani Massimiliano , Toto Ivano
Published: April 2012

During political races, candidates have to decide how to deal with the negative remarks from opposing candidates: just ignore or counterattack? In two studies, we investigated some of the consequences of this choice. In Study 1, participants were presented with a political candidate who systematically attacked his opponent and with the reactions of the attacked candidate: across conditions, the attacked candidate only focused on his political program or counterattacked. Results showed an overt condemnation of the choice to counterattack but a higher spontaneous conformity toward the candidate who counterattacked. Study 2 replicated and extended these results indicating that the gender of the attacked candidate did not affect the results. Moreover, Study 2 showed that conformity toward the attacked candidate was positively related to the predicted chances of winning the election. Results are discussed in relation to their theoretical and applied implications. Copyright © 2012 John Wiley & Sons, Ltd.
Influence of arylamine n‐acetyltransferase, sex, and age on 4‐aminobiphenyl‐induced in vivo mutant frequencies and spectra in mouse liver
Authors: Wang Shuang , Sugamori Kim S. , Brenneman Debbie , Hsu Ivy , Calce Adriana , Grant Denis M.
Published: April 2012

One model for cancer initiation by 4‐aminobiphenyl (ABP) involves N‐oxidation by cytochrome P450 CYP1A2 followed by O‐conjugation by N‐acetyltransferase(s) NAT1 and/or NAT2 and decomposition to a DNA‐binding nitrenium ion. We recently observed that neonatal ABP exposure produced liver tumors in male but not in female mice, and that NAT deficiency reduced liver tumor incidence. However, ABP‐induced liver tumor incidence did not correlate with liver levels of N‐(deoxyguanosin‐8‐yl)‐ABP adducts 24 hr after exposure. In this study, we compared in vivo ABP‐induced DNA mutant frequencies and spectra between male and female wild‐type and NAT‐deficient Muta™Mouse using both the tumor‐inducing neonatal exposure protocol and a 28‐day repetitive dosing adult exposure protocol. ABP produced an increase in liver DNA mutant frequencies in both neonates and adults. However, we observed no sex or strain differences in mutant frequencies in neonatally exposed mice, and higher frequencies in adult females than males. Neonatal ABP exposure of wild‐type mice increased the proportion of G‐T transversions in both males and females, while exposure of Nat1/2(‐/‐) mice produced increased G‐T transversions in males and a decrease in females, even though females had higher levels of N‐(deoxyguanosin‐8‐yl)‐4‐ABP adducts. There was no correlation of mutant frequencies or spectra between mice dosed as neonates or as adults. These results suggest that observed sex‐ and NAT‐dependent differences in ABP‐induced liver tumor incidence in mice are not due to differences in either mutation rates or mutational spectra, and that mechanisms independent of carcinogen bioactivation, covalent DNA binding and mutation may be responsible for these differences. Environ. Mol. Mutagen., 2012. © 2012 Wiley Periodicals, Inc.
Mutagenicity and DNA adduct formation by aristolochic acid in the spleen of Big Blue® rats
Authors: McDaniel L. Patrice , Elander Elizabeth R. , Guo Xiaoqing , Chen Tao , Arlt Volker M. , Mei Nan
Published: April 2012

Aristolochic acid (AA) is a potent human nephrotoxin and carcinogen. We previously reported that AA treatment resulted in DNA damage and mutation in the kidney and liver of rats. In this study, we have determined the DNA adducts and mutations induced by AA in rat spleen. Big Blue® transgenic rats were gavaged with 0, 0.1, 1.0, and 10.0 mg AA/kg body weight five‐times/week for 3 months. Three DNA adducts, [7‐(deoxyadenosin‐N6‐yl)‐aristolactam I, 7‐(deoxyadenosin‐N6‐yl)‐aristolactam II and 7‐(deoxyguanosin‐N2‐yl)‐aristolactam I], were identified by 32P‐postlabeling. Over the dose range studied, there were strong linear dose‐responses for AA‐DNA adduct formation in the treated rat spleens, ranging from 4.6 to 217.6 adducts/108 nucleotides. Spleen cII mutant frequencies also increased in a dose‐dependent manner, ranging from 32.7 to 286.2 × 10−6 in the treated animals. Mutants isolated from the different treatment groups were sequenced; analysis of the resulting spectra indicated that there was a significant difference between the pattern of mutation in the 10 mg/kg AA‐treated and the vehicle control rats. A:T → T:A transversion was the major type of mutation in AA‐treated rats, whereas G:C → A:T transition was the main type of mutation inthe vehicle controls. These results indicate that AA is genotoxic in the spleen of rats exposed under conditions that result in DNA adduct formation and mutation induction in kidney and liver. Environ. Mol. Mutagen., 2012. © 2012 Wiley Periodicals, Inc.
Mitogen‐activated protein kinase p38 regulates krox‐20 to direct schwann cell differentiation and peripheral myelination
Authors: Hossain Shireen , de la Cruz‐Morcillo Miguel‐Angel , Sanchez‐Prieto Ricardo , Almazan Guillermina
Published: April 2012

We previously reported that addition of extracellular matrix (ECM) extracts to rat Schwann cell‐dorsal root ganglion neuron (DRGN) co‐cultures activated mitogen‐activated protein kinase (MAPK) p38, whereas inhibition blocked myelination. Here, we used p38 pharmacological inhibitors and gene silencing to assess their effects on downstream kinases and key transcription factors. We show that p38α regulates expression of the master transcription factor, Krox‐20, required for the onset of myelination in Schwann cell‐DRGNs, as assessed by immunocytochemistry and qRT‐PCR. p38 activity is also required for the expression of the cell cycle inhibitor p27kip1, associated with Schwann cell differentiation. Three potential effectors of p38 were explored: MAPK‐activated protein kinase‐2 (MK2), mitogen and stress‐activated protein kinase‐1 (MSK‐1), and the transcription factor cAMP response element‐binding protein (CREB). Inhibition of MK2 with CMPD1 or gene knockdown with siRNAs reduced numbers of Krox‐20‐positive Schwann cells and expression of myelin proteins MBP and MAG. ECM activated CREB and increased Krox‐20 expression, whereas CREB1 gene silencing reduced Krox‐20. Furthermore, two nonselective inhibitors of MSK‐1 (H89 and R0‐318820) decreased ECM‐induced CREB phosphorylation and, similar to anti‐MSK‐1 siRNAs, reduced Krox‐20‐positive cells. In addition, p38 modulated the expression of two transcription factors involved in the regulation of Krox‐20 [suppressed cAMP‐inducible protein (SCIP) and Sox10], but not Sox2, an antagonist of Krox‐20. Collectively, our results show that p38 primarily directs Schwann cell differentiation and peripheral myelination by regulating Krox‐20 expression through its downstream effectors, MK2 and MSK‐1/CREB, and transcription factors SCIP and Sox10. © 2012 Wiley Periodicals, Inc.
TGF‐β signaling through SMAD2/3 induces the quiescent microglial phenotype within the CNS environment
Authors: Abutbul Shai , Shapiro Jenny , Szaingurten‐Solodkin Irit , Levy Nitzan , Carmy Yaron , Baron Rona , Jung Steffen , Monsonego Alon
Published: April 2012

Microglia are myeloid‐derived cells that colonize the central nervous system (CNS) at early stages of development and constitute up to 20% of the glial populations throughout life. While extensive progress has been recently made in identifying the cellular origin of microglia, the mechanism whereby the cells acquire the unique ramified and quiescent phenotype within the CNS milieu remains unknown. Here, we show that upon co‐culturing of either CD117+/Lin− hematopoietic progenitors or CD11c+ bone marrow derived cells with organotypic hippocampal slices or primary glia, the cells acquire a ramified morphology concomitant with reduced levels of CD86, MHCII, and CD11c and up‐regulation of the microglial cell–surface proteins CX3CR1 and Iba‐1. We further demonstrate that the transforming growth factor beta (TGF‐β) signaling pathway via SMAD2/3 phosphorylation is essential for both primary microglia and myeloid‐derived cells in order to acquire their quiescent phenotype. Our study suggests that the abundant expression of TGF‐β within the CNS during development and various inflammatory processes plays a key role in promoting the quiescent phenotype of microglia and may thus serve as a target for therapeutic strategies aimed at modulating the function of microglia in neurodegenerative diseases such as Alzheimer's and prion. © 2012 Wiley Periodicals, Inc.
An 80‐year record of sediment quality in the lower Mississippi River
Authors: Van Metre Peter C. , Horowitz Arthur J.
Published: April 2012

In 1937, the US Army Corps of Engineers cut through the “neck” of a large meander on the lower Mississippi River (below the confluence with the Ohio River) forming the Caulk Neck cutoff and creating Lake Whittington, a 26‐km long oxbow lake, in northern Mississippi. Since 1938, seasonal flooding and a boat channel connecting the lake with the Mississippi River have led to sediment accumulation in the lake, resulting in an 80‐year record of sediment quality in the river. On the basis of an age‐dated sediment core from the lake, trends in trace metals and hydrophobic organic compounds (except polycyclic aromatic hydrocarbons) follow well‐known patterns with upward trends from the 1930s to the ca 1970s, followed by downward trends to the present. Two factors contribute to these patterns: reservoir construction and changes in emissions. The construction of seven large reservoirs on the Missouri River, in particular the closure of the Fort Randall (1953) and Gavins Point (1955) Dams, greatly reduced the load of relatively clean sediment to the Mississippi River, likely contributing to downstream increases in contaminant concentrations in the Mississippi River. Increasing anthropogenic emissions also contributed to upward trends until ca 1970 when major environmental policy actions began resulting in broad decreases in emissions and downward trends in the concentrations of most of the contaminants monitored. Polycyclic aromatic hydrocarbons and phosphorus are partial exceptions to this pattern, with increases to the 1960s and variable concentrations showing no clear trend since. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.
Influence of DNA repair gene polymorphisms on prognosis in inoperable non‐small cell lung cancer patients treated with radiotherapy and platinum‐based chemotherapy
Authors: Butkiewicz Dorota , Drosik Anna , Suwiński Rafał , Krześniak Małgorzata , Rusin Marek , Kosarewicz Agata , Rachtan Jadwiga , Matuszczyk Iwona , Gawkowska‐Suwińska Marzena
Published: April 2012

Polymorphisms in DNA repair genes may modulate not only an individual DNA repair capacity, DNA damage levels and cancer risk but also clinical outcome after DNA damage‐inducing anticancer therapy. In this study, we analyzed the association between the XPA ‐4G>A, XPD Asp312Asn, hOGG1 Ser326Cys, XRCC1 Arg399Gln, XRCC2 ‐4234G>C, XRCC3 ‐4541A>G and Thr241Met polymorphisms and prognosis in 250 inoperable non‐small cell lung cancer (NSCLC) patients treated with radiotherapy and platinum‐based chemotherapy. In univariate model, the XPA‐4A and XRCC1 399Gln alleles alone and in combination influenced survival only in stage III group. In multivariate analysis, the XPA‐4 GA/AA was associated with poor survival (HR 1.55, p = 0.011 overall and HR 1.72, p = 0.008 in stage III). In chemoradiotherapy group, the XPA‐4A carriers were at increased risk of death and progression (HR 1.73, p = 0.013 and HR 1.65, p = 0.016, respectively), especially in stage III (p = 0.008). Moreover, individuals with ≥ 2 XPA/XRCC1 adverse alleles showed a higher risk of death (HR 1.46, p = 0.036 overall; HR 1.85, p = 0.004 in stage III and HR 1.71, p = 0.022 in chemoradiotherapy group) and progression (HR 1.75, p = 0.011 overall and HR 1.93, p = 0.005 in stage III). The XPA‐4 GA/AA genotype individually and together with the XRCC1 399Gln was an independent unfavorable prognostic factor in our study. Thus, our findings indicate a prognostic potential of the XPA‐4G>A in unresected NSCLC treated with radiotherapy and chemoradiotherapy. The results require validation in an independent population.
Small median tumor diameter at cure threshold (<20 mm) among aggressive non‐small cell lung cancers in male smokers predicts both chest X‐ray and CT screening outcomes in a novel simulation framework
Authors: Goldwasser Deborah L. , Kimmel Marek
Published: April 2012

The effectiveness of population‐wide lung cancer screening strategies depends on the underlying natural course of lung cancer. We evaluate the expected stage distribution in the Mayo CT screening study under an existing simulation model of non‐small cell lung cancer (NSCLC) progression calibrated to the Mayo lung project (MLP). Within a likelihood framework, we evaluate whether the probability of 5‐year NSCLC survival conditional on tumor diameter at detection depends significantly on screening detection modality, namely chest X‐ray and computed tomography. We describe a novel simulation framework in which tumor progression depends on cellular proliferation and mutation within a stem cell compartment of the tumor. We fit this model to randomized trial data from the MLP and produce estimates of the median radiologic size at the cure threshold. We examine the goodness of model fit with respect to radiologic tumor size and 5‐year NSCLC survival among incident cancers in both the MLP and Mayo CT studies. An existing model of NSCLC progression under‐predicts the number of advanced‐stage incident NSCLCs among males in the Mayo CT study (p‐value = 0.004). The probability of 5‐year NSCLC survival conditional on tumor diameter depends significantly on detection modality (p‐value = 0.0312). In our new model, selected solution sets having a median tumor diameter of 16.2–22.1 mm at cure threshold among aggressive NSCLCs predict both MLP and Mayo CT outcomes. We conclude that the median lung tumor diameter at cure threshold among aggressive NSCLCs in male smokers may be small (<20 mm).
Quantification of PKC family genes in sporadic breast cancer by qRT‐PCR: Evidence that PKCι/λ overexpression is an independent prognostic factor
Authors: Awadelkarim Khalid Dafaallah , Callens Céline , Rossé Carine , Susini Aurélie , Vacher Sophie , Rouleau Etienne , Lidereau Rosette , Bièche Ivan
Published: April 2012

Drugs targeting protein kinase C (PKC) show promising therapeutic activity. However, little is known about the expression patterns of the 11 PKC genes in human tumors, and the clinical significance of most PKC genes is unknown. We used qRT‐PCR assays to quantify mRNA levels of the 11 PKC genes in 458 breast tumors from patients with known clinical/pathological status and long‐term outcome. The proportion of tumors in which the expression of the different genes was altered varied widely, from 9.6% for PKN2 to 40.2% for PKCι/λ. In breast tumors, overexpression was the main alteration observed for PKCι/λ (33.4%), PKCδ (29.5%) and PKCζ (9.6%), whereas underexpression was the main alteration observed for PKCα (27.3%), PKCε (11.6%), PKCη (8.7%) and PKN2 (8.1%). Both overexpression and underexpression were observed for PKCβ (underexpression 15.5%, overexpression 13.8%), PKCθ (underexpression 14.8%, overexpression 10.0%) and PKN1 (underexpression 6.6%, overexpression 7.4%). Several links were found between different PKC genes; and also between the expression patterns of PKC genes and several classical pathological and clinical parameters. PKCι/λ alone was found to have prognostic significance (p = 0.043), whereas PKCα showed a trend towards an influence on relapse‐free survival (p = 0.052). PKCι/λ retained its prognostic significance in Cox multivariate regression analysis (p = 0.031). These results reveal very complex expression patterns of PKC genes in breast tumors, and suggest that their expression should be considered together when evaluating anti‐tumoral drugs. PKCι/λ seems to be the most promising therapeutic target in breast cancer.
Body size and risk of differentiated thyroid carcinomas: Findings from the EPIC study
Authors: Rinaldi Sabina , Lise Mauro , Clavel‐Chapelon Françoise , Boutron‐Ruault Marie‐Christine , Guillas Gwenaelle , Overvad Kim , Tjønneland Anne , Halkjær Jytte , Lukanova Annekatrin , Kaaks Rudolf , Bergmann Manuela M. , Boeing Heiner , Trichopoulou Antonia , Zylis Dimosthenis , Valanou Elissavet , Palli Domenico , Agnoli Claudia , Tumino Rosario , Polidoro Silvia , Mattiello Amalia , Bas Bueno‐de‐Mesquita H. , Peeters Petra H. , Weiderpass Elisabete , Lund Eiliv , Skeie Guri , Rodríguez Laudina , Travier Noemie , Sánchez Maria‐José , Amiano Pilar , Huerta José‐María , Ardanaz Eva , Rasmuson Torgny , Hallmans Göran , Almquist Martin , Manjer Jonas , Tsilidis Konstantinos K. , Allen Naomi E. , Khaw Kay‐Tee , Wareham Nick , Byrnes Graham , Romieu Isabelle , Riboli Elio , Franceschi Silvia
Published: April 2012

Results from case‐control and prospective studies suggest a moderate positive association between obesity and height and differentiated thyroid carcinoma (TC). Little is known on the relationship between other measures of adiposity and differentiated TC risk. Here, we present the results of a study on body size and risk of differentiated TC based on a large European prospective study (EPIC). During follow‐up, 508 incident cases of differentiated TC were identified in women, and 58 in men. 78% of cases were papillary TC. Cox proportional hazard models were used to estimate hazard ratios (HRs). In women, differentiated TC risk was significantly associated with body mass index (BMI, kg/m2) (HR highest vs lowest quintile = 1.41, 95% CI: 1.03–1.94); height (HR = 1.61; 95% CI: 1.18–2.20); HR highest vs lowest tertile waist (HR = 1.34, 95% CI: 1.00–1.79) and waist‐to‐hip ratio (HR = 1.42, 95% CI: 1.05–1.91). The association with BMI was somewhat stronger in women below age 50. Corresponding associations for papillary TC were similar to those for all differentiated TC. In men the only body size factors significantly associated with differentiated TC were height (non linear), and leg length (HR highest vs. lowest tertile = 3.03, 95% CI: 1.30–7.07). Our study lends further support to the presence of a moderate positive association between differentiated TC risk and overweight and obesity in women. The risk increase among taller individuals of both sexes suggests that some genetic characteristics or early environmental exposures may also be implicated in the etiology of differentiated TC.
Catalytic Activity and Performance of Copper‐Based Complexes Mediating Atom Transfer Radical Polymerization
Authors: Tsarevsky Nicolay V.
Published: April 2012

The factors affecting the performance of the atom transfer radical polymerization (ATRP) catalyst, i.e., its activity, ability to control the polymerization, and its propensity to participate in side complexation or redox reactions are summarized in this brief review. The effect of the ligand, transferable halogen atom, and the reaction solvent can be understood and quantified by formally splitting the overall atom transfer equilibrium into contributing reactions, including the homolysis of a carbonhalogen bond, reduction of the halogen atom to a halide ion (electron affinity), oxidation of the lower oxidation state metal complex (activator), and formation of the radical deactivator via coordination of a halide anion to the higher oxidation state metal complex (halidophilicity).
Polymers with Esters of Phosphoric Acid Units: From Synthesis, Models of Biopolymers to PolymerInorganic Hybrids
Authors: Penczek Stanislaw , Pretula Julia B. , Kaluzynski Krzysztof , Lapienis Grzegorz
Published: April 2012

Syntheses, some properties, and applications of the poly(alkylene phosphate)s prepared either by ring‐opening polymerization (ROP) or by polycondensation are described mostly on the basis of the data from our laboratories. The ROP of some cyclic phosphates and H‐phosphonates are living and/or controlled process. Transesterification of the products of the reaction of an excess of dimethylphosphonate with glycols leads to polymers with Mn close to 5×104. Poly(alkylene phosphate)s with five or six atoms in repeating units bear resemblance to the main chains of nucleic and teichoic acids. These and similar poly(alkylene phosphate)s with different repeating units were used as liquid membranes for the efficient separation of cations as well as to modify the medium for CaCO3 crystallization. In this latter process, a diblock copolymer with ionic and nonionic block was used. Poly(alkylene phosphate)s constituted the ionic block and the nonionic block was formed from poly(ethylene glycol); together with CaCO3 polymerinorganic hybrids were formed.
Remifentanil impairs sperm motility reversibly in vitro
Authors: Xu Bo
Published: April 2012

The study is to observe the effects of remifentanil on human sperm motility in vitro. After spermatozoa were washed and resuspended in Ham's F‐10 medium, the washed human sperm suspensions were treated in vitro with different concentrations of remifentanil for 30 min. Sperm motility was assessed by computer‐assisted sperm analysis at 5, 10, 15, and 30 min. Remifentanil significantly decreased (a + b) grade spermatozoa, between 5 and 10 min at the concentrations ranging from 0.1 to 100 μg L ‐ 1 in a dose‐dependent manner and effects no significant difference at 15 and 30 min as compared with control groups. The results suggest that there is indication that this drug has short‐term effect on sperm motility. © 2012 Wiley Periodicals, Inc. J Biochem Mol Toxicol 26:176–177, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.21408
Malabaricone C inhibits PDGF‐induced proliferation and migration of aortic smooth muscle cells through induction of heme oxygenase‐1
Authors: Lee Suhyun , Seo Juhee , Ryoo Sungwoo , Cuong To Dao , Min Byung‐Sun , Lee Jeong‐Hyung
Published: April 2012

Malabaricone C (Mal‐C), isolated from nutmeg, is known to exert a variety of pharmacological activities. However, the effect of Mal‐C on vascular smooth muscle cells (VSMCs) is unknown. This study examined the effect of Mal‐C on proliferation and migration of primary rat aortic smooth muscle cells (RASMCs) as well as its underlying mechanisms. Treatment of RASMCs with Mal‐C induced both protein and mRNA expression of heme oxygenase‐1 (HO‐1) in a dose‐ and time‐dependent manner. Mal‐C‐mediated HO‐1 induction was inhibited by treatment with actinomycin D or by cycloheximide. SB203580 (a p38 inhibitor), SP600125 (a JNK inhibitor), U0126 (a MEK inhibitor), and N‐acetylcysteine (NAC, an antioxidant) did not suppress Mal‐C‐induced HO‐1 expression. In contrast, LY294002 (a PI3K inhibitor) blocked Mal‐C‐induced HO‐1 expression. Moreover, RASMCs treated with Mal‐C exhibited activation of AKT in a dose‐ and time‐dependent manner. Treatment of RASMCs with Mal‐C increased nuclear translocation of nuclear factor‐E2‐related factor 2 (Nrf2), which is a key regulator of HO‐1 expression, and this translocation was also inhibited by LY294002. Consistent with the notion that HO‐1 has protective effects against VSMCs, Mal‐C remarkably inhibited platelet‐derived growth factor (PDGF)‐induced proliferation and migration of RASMCs. However, inhibition of HO‐1 significantly attenuated the inhibitory effects of Mal‐C on PDGF‐induced proliferation and migration of RASMCs. Taken together, these findings suggest that Mal‐C could suppress PDGF‐induced proliferation and migration of RASMCs through Nrf2 activation and subsequent HO‐1 induction via the PI3K/AKT pathway, and may be a potential HO‐1 inducer for preventing or treating vascular diseases. J. Cell. Biochem. 113: 2866–2876, 2012. © 2012 Wiley Periodicals, Inc.
Ric‐8: Different cellular roles for a heterotrimeric G‐protein GEF
Authors: Hinrichs M.V. , Torrejón M. , Montecino M. , Olate J.
Published: April 2012

Signaling via heterotrimeric G‐proteins is evoked by agonist‐mediated stimulation of seven transmembrane spanning receptors (GPCRs). During the last decade it has become apparent that Gα subunits can be activated by receptor‐independent mechanisms. Ric‐8 belongs to a highly conserved protein family that regulates heterotrimeric G‐protein function, acting as a non‐canonical guanine nucleotide exchange factors (GEF) over a subset of Gα subunits. In this review we discuss the roles of Ric‐8 in the regulation of diverse cell functions, emphasizing the contribution of its multiple domain protein structure in these diverse functions. J. Cell. Biochem. 113: 2797–2805, 2012. © 2012 Wiley Periodicals, Inc.
Antithrombotic and profibrinolytic activities of eckol and dieckol
Authors: Kim Tae Hoon , Ku Sae‐Kwang , Bae Jong‐Sup
Published: April 2012

In order to develop new anticoagulant agents, two single compounds (eckol and dieckol) were isolated from Eisenia bicyclis and examined their anticoagulant activities by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT) as well as cell‐based thrombin and activated factor X (FXa) generation activities. And the effects of eckol and dieckol on the expression of plasminogen activator inhibitor type 1 (PAI‐1) and tissue‐type plasminogen activator (t‐PA) were tested in tumor necrosis factor‐α (TNF‐α) activated human umbilical vein endothelial cells (HUVECs). Data showed that eckol and dieckol prolonged aPTT and PT significantly and inhibited thrombin and FXa activities. They also inhibited the generation of thrombin or FXa in HUVECs. In accordance with these anticoagulant activities, eckol or dieckol showed anticoagulant effect in vivo. Furthermore, eckol and dieckol inhibited TNF‐α induced PAI‐1 production and the ratio between PAI‐1 and t‐PA was found to be significantly decreased by eckol and dieckol. Surprisingly, these anticoagulant and profibrinolytic effects of dieckol were better than those of eckol indicating that hydroxyl group in eckol positively regulated anticoagulant function of eckol. Therefore, these results suggest that eckol or dieckol possesses antithrombotic activities and provides a possibility to develop as an agent for the anticoagulation. J. Cell. Biochem. 113: 2877–2883, 2012. © 2012 Wiley Periodicals, Inc.
Junctophilin 2 knockdown interfere with mitochondrium status in ESC‐CMs and cardiogenesis of ES cells
Authors: Liang Xingguang , Mei Yuqin , Huang Xin , Shen Guofang , Zhu Danyan , Yu Yongping , Wang Jianan , Lou Yijia
Published: April 2012

In the present study, we explored the possible links between Junctophilin 2 (Jp2) and the mitochondrium‐sarcoplasmic reticulum (SR) interaction in embryonic stem cell‐derived cardiomyocytes (ESC‐CMs), as well as the role of Jp2 in cardiogenesis of ES cells. We found that Ca2+ transient was abnormal and mitochondria were de‐energized within siJp2 ESC‐CMs. The essential juxtaposition structure of mitochondrium with SR was destroyed accompanied by selectively downregulation of Pgc‐1α, Nrf‐1, and Mfn‐2. Impaired co‐localization of the JP2 and sarcomeres (α‐Actinin or Troponin‐T) appeared in embryoid bodies (EBs) after Jp2 knockdown. Calsequestrin2 and ryanodine receptor 2 within SR were expressed as early as the initiation of differentiation, while triadin and caveolin3 within t‐tubules (TTs) did not appear until the terminal, indicating that JP2 probably did not contribute to anchoring the SR to TTs at the early cardiogenesis stage as usual. In addition, Jp2 knockdown selectively decreased gene transcription toward cardiogenesis (Brachyury, Isl1, and Nkx2.5), subsequently weaken EB beating activity by 60%. Taken together, reducing JP2 expression in ESC‐CMs resulted in impaired mitochondrial status due to either abnormal cellular Ca2+ homeostasis or disturbing of juxtaposition. A sensitive time window of JP2 necessary in cardiac differentiation was found at early stage via an extra non‐TTs/SR anchor‐dependent role. J. Cell. Biochem. 113: 2884–2894, 2012. © 2012 Wiley Periodicals, Inc.
IL‐17 mediates estrogen‐deficient osteoporosis in an Act1‐dependent manner
Authors: DeSelm Carl J. , Takahata Yoshifumi , Warren Julia , Chappel Jean C. , Khan Taimur , Li Xiaoxia , Liu Caini , Choi Yongwon , Kim Youngmi Faith , Zou Wei , Teitelbaum Steven L.
Published: April 2012

Estrogen‐deficient osteoporosis may be an inflammatory disorder and we therefore asked if IL‐17 participates in its pathogenesis. Deletion of the principal IL‐17 receptor (IL‐17RA) protects mice from ovariectomy (OVX)‐induced bone loss. Further supporting a central role of IL‐17 in its pathogenesis, OVX‐induced osteoporosis is prevented by a blocking antibody targeting the cytokine. IL‐17 promotes osteoclastogenesis by stimulating RANK ligand (RANKL) expression by osteoblastic cells, mediated by the IL‐17RA SEFIR/TILL domain. Estrogen deprivation, however does not enhance IL‐17RA mRNA expression by osteoblasts or in bone, but augments that of Act1, an IL‐17RA‐interacting protein and signaling mediator. Similar to IL‐17RA−/− mice, those lacking Act1 are protected from OVX‐induced bone loss. Also mirroring IL‐17RA‐deficiency, absence of Act1 in osteoblasts, but not osteoclasts, impairs osteoclastogenesis via dampened RANKL expression. Transduction of WT Act1 into Act1−/− osteoblasts substantially rescues their osteoclastogenic capacity. The same construct, however, lacking its E3 ligase U‐box or its SEFIR domain, which interacts with its counterpart in IL‐17RA, fails to do so. Estrogen deprivation, therefore, promotes RANKL expression and bone resorption in association with upregualtion of the IL‐17 effector, Act1, supporting the concept that post‐menopausal osteoporosis is a disorder of innate immunity. J. Cell. Biochem. 113: 2895–2902, 2012. © 2012 Wiley Periodicals, Inc.
The influence of obesity on the assessment of carotid intima‐media thickness
Authors: Gállego Pérez‐Larraya Jaime , Irimia Pablo , Martínez‐Vila Eduardo , Barba Joaquín , Guembe María Jesús , Varo Nerea , Castellano José María , Viñes José Javier , Díez Javier
Published: April 2012

Background.

The assessment of carotid intima‐media thickness (CIMT) may improve cardiovascular risk prediction. The optimal protocol for CIMT measurement is unclear. CIMT may be measured in the common carotid artery (CCA), carotid bifurcation (CB), and internal carotid artery (ICA), but measurements from CB and ICA are more difficult to obtain. We studied the influence of body mass index (BMI) and atheroma plaques on the capacity to obtain CIMT measurements at different carotid sites.

Methods.

Using an automatic system, CIMT was measured in 700 subjects aged 45–75, in the near and far walls of CCA, CB, and ICA bilaterally. The presence of atheroma plaques, BMI and vascular risk factors were recorded.

Results.

CIMT measurements in CCA were possible in all except one subject. It was not possible to obtain CIMT measurements at CB or ICA in 24.1% of normal weight and 58.8% of obese subjects. The likelihood of obtaining CIMT measurement at all carotid sites decreased as the BMI increased. Atheroma plaques in a carotid segment did not preclude CIMT measurement at this site.

Conclusions.

CIMT measurements in distal carotid segments are more challenging in obese subjects. Measuring CIMT at CCA remains feasible in obese subjects and should be the primary endpoint in these subjects. Nevertheless, CB and ICA measurements, when feasible, would improve risk classification. © 2012 Wiley Periodicals, Inc. J Clin Ultrasound 40:479–485, 2012