bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanism of neuroprotection by donepezil pretreatment in rat cortical neurons chronically treated with donepezil
Authors: Takada‐Takatori Yuki , Kume Toshiaki , Ohgi Yuta , Izumi Yasuhiko , Niidome Tetsuhiro , Fujii Takeshi , Sugimoto Hachiro , Akaike Akinori
Published: July 2008

Previously, we showed that in rat cortical neurons, chronic donepezil treatment (10 μM, 4 days) up‐regulates nicotinic receptors (nAChR) and makes neurons more sensitive to the neuroprotective effect of donepezil. Here we examined the mechanism of donepezil‐induced neuroprotection in neurons chronically treated with donepezil. The mechanism of neuroprotection was examined under different conditions of exposure to glutamate, acute and moderate, that induce cell death associated with necrotic and apoptotic cell death, respectively. Concomitant treatment with antagonists of nAChRs but not muscarinic receptors inhibited donepezil pretreatment‐induced neuroprotection against acute glutamate treatment‐induced death. Donepezil pretreatment prevented acute glutamate‐ and ionomycin‐induced neurotoxicity, but notS‐nitrosocysteine‐induced neurotoxicity, suggesting that donepezil protects neurons via nAChR at levels before nitric oxide synthase activation against acute glutamate neurotoxicity. Concomitant treatment with antagonists of nAChR or phosphatidylinositol 3‐kinase (PI3K) signaling inhibitors significantly inhibited neuroprotection against moderate glutamate neurotoxicity and decreased the phosphorylation level of Akt. Neuroprotection was also inhibited by treatment with inhibitor of mitogen‐activated protein kinase (MAPK) kinase. These results suggest that donepezil protects neurons against moderate glutamate neurotoxicity via nAChR‐PI3K‐Akt and MAPK signaling pathways. This study provides novel insight into the mechanism of donepezil‐induced neuroprotection that involves nAChR up‐regulation. © 2008 Wiley‐Liss, Inc.
Induction of the kynurenine pathway by neurotropic influenza a virus infection
Authors: Holtze Maria , Asp Linnéa , Schwieler Lilly , Engberg Göran , Karlsson Håkan
Published: July 2008

Glutamatergic NMDA (N‐methylD‐aspartate) receptors play a critical role in brain development and neurotransmission. Kynurenic acid, an end product of tryptophan degradation along the kynurenine pathway, is an endogenous NMDA receptor antagonist. In the present study, the effects of neurotropic influenza A virus infection on the kynurenine pathway were investigated in mouse brain primary cell cultures and in mouse brain after infection on day 3 of postnatal life. Altered levels of transcripts encoding several key enzymes of the kynurenine pathway were observed in infected neuron and glial cell cultures. In vivo, changes in the levels of such transcripts in brain were observed on postnatal days 7 and 13 but not on day 24. On postnatal day 13, infiltrating T lymphocytes and increased levels of kynurenic acid were observed in the brains of the infected animals. Taken together, the present results indicate that central nervous system infections during early life can activate the entire kynurenine pathway. Such activation is likely to result in the generation of several bioactive metabolites, as supported by our finding of a transient increase of kynurenic acid. In light of its antagonistic actions on the NMDA receptor, kynurenic acid can potentially link infections with glutamatergic signaling in the developing brain. © 2008 Wiley‐Liss, Inc.
Global gene expression analysis of cranial neural tubes in embryos of diabetic mice
Authors: Jiang Boran , Kumar S. Dinesh , Loh Wan Ting , Manikandan J. , Ling Eng‐Ang , Tay Samuel S. W. , Dheen S. Thameem
Published: July 2008

Maternal diabetes causes congenital malformations in various organs including the neural tube in fetuses. In this study, we have analyzed the differential gene expression profiling in the cranial neural tube of embryos from diabetic and control mice by using the oligonucleotide microarray. Expression patterns of genes and proteins that are differentially expressed in the cranial neural tube were further examined by the real‐time reverse transcriptase–polymerase chain reaction, in situ hybridization, and immunohistochemistry. Proliferation index and apoptosis were examined by BrdU (5‐bromo‐2‐deoxyuridine) labeling and TUNEL (terminal deoxynucleotidyl transferase dUTP nick‐end labeling) assay, respectively. Embryos (E11.5) of diabetic pregnancies displayed distortion in neuroepithelia of the cranial neural tube. Microarray analysis revealed that a total of 390 genes exhibited more than twofold changes in expression level in the cranial neural tube of embryos from diabetic mice. Several genes involving apoptosis, proliferation, migration, and differentiation of neurons in the cranial neural tube were differentially expressed in embryos of diabetic pregnancy. In addition, maternal diabetes perturbed the development of choroid plexus and ventricular systems and reduced the production of proteins such as Ttr and Igf2 in the developing brain, indicating that these changes could impair the survival and proliferation of neuroepithelial cells and neurogenesis in embryos of diabetic mice. It is concluded that altered expression of a variety of genes involved in brain development is associated with cranial neural tube dysmorphogenesis that may subsequently contribute to intellectual impairment of the offspring of a diabetic mother. © 2008 Wiley‐Liss, Inc.
Estrogen affects levels of Bcl‐2 protein and mRNA in medial amygdala of ovariectomized rats
Authors: Fan Lu , Pandey Subhash C. , Cohen Rochelle S.
Published: July 2008

The survival factor Bcl‐2 is a cyclic AMP response element‐binding protein (CREB) gene product implicated in mediating some of estrogen's effects on neuroprotection. Previously, we showed an effect of estradiol benzoate (E) on numbers of neuron‐specific protein (NeuN)‐ and phosphorylated CREB (pCREB)‐positive cells in medial (MeA), but not central (CeA), amygdala of ovariectomized rats. To determine whether these effects are accompanied by an E‐induced increase in Bcl‐2, we examined the effects of E on levels of Bcl‐2 protein and mRNA in MeA and CeA of ovariectomized rats treated with E regimens resulting in moderate (2.5 μg E for 4 or 14 days) or high (10 μg E for 14 days) plasma estradiol levels. As a physiological control, we showed that all E treatments increased uterine wet weight relative to vehicle; 10 μg E for 14 days also increased uterine weight compared with that seen with lower E levels. Western blot analysis revealed that all E groups displayed an increase in uterine Bcl‐2 protein levels compared with vehicle. We found that 2.5 μg and 10 μg E for 14 days increased levels of Bcl‐2 gold immunolabeling compared with vehicle and 2.5 μg E for 4 days in MeA, but not CeA. We measured Bcl‐2 mRNA levels in vehicle and 2.5 μg E‐treated 14‐day groups. There was a significant increase in Bcl‐2 mRNA levels in MeA, but not CeA, of E‐treated ovariectomized rats compared with vehicle controls. The E‐induced increase in protein and mRNA levels of Bcl‐2 in MeA may be important for neuroprotection in this region. © 2008 Wiley‐Liss, Inc.
Intrathecal administration of sigma‐1 receptor agonists facilitates nociception: Involvement of a protein kinase C–dependent pathway
Authors: Roh Dae‐Hyun , Kim Hyun‐Woo , Yoon Seo‐Yeon , Seo Hyoung‐Sig , Kwon Young‐Bae , Kim Kee‐Won , Han Ho‐Jae , Beitz Alvin J. , Lee Jang‐Hern
Published: July 2008

Sigma sites, originally proposed as opioid receptor subtypes, are currently thought to represent unique receptors with a specific pattern of drug selectivity, a well‐established anatomical distribution and broad range of functional roles including potential involvement in nociceptive mechanisms. We have recently demonstrated that intrathecal (i.t.) treatment with a sigma‐1 receptor antagonist reduced formalin‐induced pain behavior. In the present study, we investigated the potential role of spinal sigma‐1 receptor agonists in peripherally initiated nociception and attempted to elucidate intracellular signaling mechanisms associated with spinal cord sigma‐1 receptor activation in mice. The i.t. injection of the sigma‐1 receptor agonists PRE‐084 (PRE) or carbetapentane (CAR) significantly decreased tail‐flick latency (TFL) and increased the frequency of paw withdrawal responses to mechanical stimulation (von Frey filament, 0.6 g) as well as the amount of Fos expression in the spinal cord dorsal horn induced by noxious paw‐pinch stimulation. These PRE‐ or CAR‐induced facilitatory effects on nociception were significantly blocked by i.t. pretreatment with the sigma‐1 receptor antagonist, BD‐1047, the phospholipase C (PLC) inhibitor, U‐73,122, the Ca2+‐ATPase inhibitor, thapsigargin, and the protein kinase C (PKC) inhibitor, chelerythrine. Western blot analysis further revealed that i.t. PRE or CAR injection significantly increased pan‐PKC as well as the PKCα, ϵ, and ζ isoforms in the dorsal horn. Collectively, these findings demonstrate that calcium‐dependent second messenger cascades including PKC are involved in the facilitation of nociception associated with spinal sigma‐1 receptor activation. © 2008 Wiley‐Liss, Inc.
Osteogenic potential of reamer irrigator aspirator (RIA) aspirate collected from patients undergoing hip arthroplasty
Authors: Porter Ryan M. , Liu Fangjun , Pilapil Carmencita , Betz Oliver B. , Vrahas Mark S. , Harris Mitchel B. , Evans Christopher H.
Published: July 2008

Intramedullary nailing preceded by canal reaming is the current standard of treatment for long‐bone fractures requiring stabilization. However, conventional reaming methods can elevate intramedullary temperature and pressure, potentially resulting in necrotic bone, systemic embolism, and pulmonary complications. To address this problem, a reamer irrigator aspirator (RIA) has been developed that combines irrigation and suction for reduced‐pressure reaming with temperature modulation. Osseous particles aspirated by the RIA can be recovered by filtration for use as an autograft, but the flow‐through is typically discarded. The purpose of this study was to assess whether this discarded filtrate has osteogenic properties that could be used to enhance the total repair potential of aspirate. RIA aspirate was collected from five patients (ages 71–78) undergoing hip hemiarthroplasty. Osseous particles were removed using an open‐pore filter, and the resulting filtrate (230 ± 200 mL) was processed by Ficoll‐gradient centrifugation to isolate mononuclear cells (6.2 ± 5.2 × 106 cells/mL). The aqueous supernatant contained FGF‐2, IGF‐I, and latent TGF‐β1, but BMP‐2 was below the limit of detection. The cell fraction included culture plastic‐adherent, fibroblastic cells that displayed a surface marker profile indicative of mesenchymal stem cells and that could be induced along the osteogenic, adipogenic, and chondrogenic lineages in vitro. When compared to outgrowth cells from the culture of osseous particles, filtrate cells were more sensitive to seeding density during osteogenic culture but had similar capacity for chondrogenesis. These results suggest using RIA aspirate to develop improved, clinically expeditious, cost‐effective technologies for accelerating the healing of bone and other musculoskeletal tissues. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:42–49, 2009
Surface modification of poly(dimethylsiloxane) microfluidic devices and its application in simultaneous analysis of uric acid and ascorbic acid in human urine
Authors: Liang Ru‐Ping , Gan Gui‐Hua , Qiu Jian‐Ding
Published: July 2008

A novel and simple method based on layer‐by‐layer (LBL) technique has been developed for the modification of the channel in PDMS electrophoresis microchip to create a hydrophilic surface with a stable EOF. The functional surface was obtained by sequentially immobilizing chitosan and deoxyribonucleic acid (DNA) onto the microfluidic channel surface using the LBL assembly technique. Compared to the native PDMS microchips, the contact angle of the chitosan–DNA modified PDMS microchips decreased and the EOF increased. Experimental conditions were optimized in detail. The chitosan–DNA modified PDMS microchips exhibited good reproducibility and long‐term stability. Separation of uric acid (UA) and ascorbic acid (AA) performed on the modified PDMS microchip generated 43 450 and 46 790 N/m theoretical plates compared with 4048 and 19 847 N/m with the native PDMS microchip. In addition, this method has been successfully applied to real human urine samples, without SPE, with recoveries of 97–105% for UA and AA.
Analysing the Chemical Composition Distribution of Ethylene‐Acrylate Copolymers: Comparison of HT‐HPLC, CRYSTAF and TREF
Authors: Albrecht Andreas , Brüll Robert , Macko Tibor , Sinha Pritish , Pasch Harald
Published: July 2008

HT‐HPLC is an attractive technique to analyse CCD of olefin copolymers and offers the possibility to shorten analysis times compared to fractionation techniques based on crystallisation. We have found that HT‐HPLC enables the selective elution of EMA and EBA copolymers according to their content of the polar co‐monomer. This fractionation could be confirmed by coupling the gradient HPLC system with FT‐IR spectroscopy. The CCDs obtained by this new method were then compared to the results from CRYSTAF. Both methods, HT‐HPLC and CRYSTAF, can discriminate between sets of samples having a narrow or a broad CCD. They can also prove the presence of acrylate‐poor fractions.

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ARGET ATRP of Methacrylates and Acrylates with Stoichiometric Ratios of Ligand to Copper
Authors: Chan Nicky , Cunningham Michael F. , Hutchinson Robin A.
Published: July 2008

Atom transfer radical polymerizations of butyl methacrylate, methyl methacrylate, and butyl acrylate were conducted using only ppm amounts of catalyst through the regeneration of activator via the ARGET mechanism. The polymers produced were nearly colorless, and exhibited living characteristics with copper catalyst levels as low as 6.4 ppm (relative to monomer). Polymerizations were well controlled at temperatures up to 110 °C and, contrary to previous studies, ARGET ATRP was successfully carried out using only a stoichiometric amount of ligand to catalyst. As ligand can account for a considerable portion of catalyst cost, these results demonstrate the robustness of ARGET ATRP, and its potential for industrial adoption.

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New mechanisms and therapeutic potential of curcumin for colorectal cancer
Authors: Villegas Isabel , Sánchez‐Fidalgo Susana , Alarcón de la Lastra Catalina
Published: July 2008

Curcumin is a polyphenol derived fromCurcuma longa. Over the last few years, a number of studies have provided evidence of its main pharmacological properties including chemosensitizing, radiosensitizing, wound healing activities, antimicrobial, antiviral, antifungical, immunomodulatory, antioxidant and anti‐inflammatory. More recent data provide interesting insights into the effect of this compound on cancer chemoprevention and chemotherapy. In fact, preclinical studies have shown its ability to inhibit carcinogenesis in various types of cancer including colorectal cancer (CRC). Curcumin has the capacity of interact with multiple molecular targets affecting the multistep process of carcinogenesis. Also, curcumin is able to arrest the cell cycle, to inhibit the inflammatory response and the oxidative stress and to induce apoptosis in cancer cells. Likewise, it has been shown to possess marked antiangiogenic properties. Furthermore, curcumin potentiates the growth inhibitory effect of cyclo‐oxygenase (COX)‐2 inhibitors and traditional chemotherapy agents implicating another promising therapy regimen in the future treatment of CRC. However, its clinical advance has been hindered by its short biological half‐life and low bioavailability after oral administration. This review is intended to provide the reader an update of the bioavailability and pharmacokinetics of curcumin and describes the recently identified molecular pathways responsible of its anticancer potential in CRC.
Reduced mammary tumor progression in a transgenic mouse model fed an isoflavone‐poor soy protein concentrate
Authors: Chiesa Giulia , Rigamonti Elena , Lovati Maria R. , Disconzi Emanuela , Soldati Sabina , Sacco Maria G. , Catò Enrica Mira , Patton Veronica , Scanziani Eugenio , Vezzoni Paolo , Arnoldi Anna , Locati Daniela , Sirtori Cesare R.
Published: July 2008

Dietary exposure to soy has been associated with reduced breast cancer incidence. Soy isoflavones and protein components, such as protease inhibitors and the lunasin peptide, have been indicated as potential agents reducing carcinogenesis. In this study, the effect of soy‐based diets was evaluated in a transgenic mouse model of breast carcinoma, overexpressing the neu oncogene. Neu female mice were fed for 20 wk a soy‐ and isoflavone‐free diet (IFD), 4RF21 laboratory mouse diet, soy‐based, thus isoflavone‐rich (STD), or AIN‐76‐based semisynthetic diets with a soy protein isolate (SPI) or an isoflavone‐poor soy protein concentrate (IPSP) as protein source. Mice were then sacrificed and tumors removed. Mammary tumor weights were not different in SPI versus IFD and STD fed mice. In contrast, mice fed IPSP showed reduced tumor progression versus IFD and STD groups (p < 0.05). Moreover, IPSP fed mice showed lower bromo‐2′‐deoxyuridine (BrdU) incorporation into breast tumor cells compared to STD and SPI fed animals (p < 0.02). Lung metastases were detected in 80% of IFD fed mice, in 70% of mice fed STD and SPI, and only in 50% of the IPSP fed animals. These results indicate that a diet containing an isoflavone‐poor soy protein concentrate may inhibit breast tumor progression and metastasis development.
The method of fundamental solutions applied to the calculation of eigensolutions for 2D plates
Authors: Alves Carlos J. S. , Antunes Pedro R. S.
Published: July 2008

In this paper we study the application of the method of fundamental solutions (MFS) to the numerical calculation of the eigenvalues and eigenfunctions for the 2D bilaplacian in simply connected plates. This problem was considered in Kang and Lee (J. Sound Vib. 2001; 242(1):9–16) using wave‐type functions and in Chen et al. (Eng. Anal. Boundary Elem. 2004; 28:535–545) using radial basis functions for circular and rectangular domains. The MFS is a mesh‐free method that was already applied to the calculation of the eigenvalues and eigenfunctions associated with the Laplace operator (cf. Appl. Math. Lett. 2001; 14(7):837–842; Eng. Anal. Boundary Elem. 2005; 29(2):166–174; Comput. Mater. Continua 2005; 2(4):251–266). The application of this method to the bilaplace operator was already considered in Chen and Lee (ECCOMAS Thematic Conference on Meshless Methods, Lisbon, 2005) for multiply connected domains, but only for simple shapes. Here we apply an algorithm for the choice of point‐sources, as in Alves and Antunes (Comput. Mater. Continua 2005; 2(4):251–266), which leads to very good numerical results for simply connected domains. A main part of this paper is devoted to the numerical analysis of the method, presenting a density result that justifies the application of the MFS to the eigenvalue biharmonic equation for clamped plate problems. We also present a bound for the eigenvalues approximation error, which leads to an a posteriori convergence estimate. Copyright © 2008 John Wiley & Sons, Ltd.
Application of Richardson extrapolation to the numerical solution of partial differential equations
Authors: Burg Clarence , Erwin Taylor
Published: July 2008

Richardson extrapolation is a methodology for improving the order of accuracy of numerical solutions that involve the use of a discretization size h. By combining the results from numerical solutions using a sequence of related discretization sizes, the leading order error terms can be methodically removed, resulting in higher order accurate results. Richardson extrapolation is commonly used within the numerical approximation of partial differential equations to improve certain predictive quantities such as the drag or lift of an airfoil, once these quantities are calculated on a sequence of meshes, but it is not widely used to determine the numerical solution of partial differential equations. Within this article, Richardson extrapolation is applied directly to the solution algorithm used within existing numerical solvers of partial differential equations to increase the order of accuracy of the numerical result without referring to the details of the methodology or its implementation within the numerical code. Only the order of accuracy of the existing solver and certain interpolations required to pass information between the mesh levels are needed to improve the order of accuracy and the overall solution accuracy. Using the proposed methodology, Richardson extrapolation is used to increase the order of accuracy of numerical solutions of the linear heat and wave equations and of the nonlinear St. Venant equations in one‐dimension. © 2008 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2009
Exact solutions for nonlinear Burgers' equation by homotopy perturbation method
Authors: Biazar J. , Ghazvini H.
Published: July 2008

The aim of this article is to construct a new efficient recurrent relation to solve nonlinear Burgers' equation. The homotopy perturbation method is used to solve this equation. Because Burgers' equation arises in many applications, it is worth trying new solution methods. Comparison of the results with those of Adomian's decomposition method leads to significant consequences. Four standard problems are used to illustrate the method. © 2008 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2009
Chemical incorporation of copper into indium selenide thin‐films for processing of CuInSe2 solar cells
Authors: Hibberd C. J. , Ernits K. , Kaelin M. , Müller U. , Tiwari A. N.
Published: July 2008

A chemical method of incorporating copper into indium selenide thin‐films has been investigated, with the goal of creating a precursor structure for conversion into CuInSe2 (CIS) layers suitable for solar cell processing. The precursor and converted layers have been investigated with scanning electron microscopy (SEM), X‐ray diffraction (XRD), Raman spectroscopy and X‐ray photoelectron spectroscopy (XPS). From these measurements, the incorporation of copper into the indium selenide layers is concluded to proceed by an ion‐exchange reaction. This reaction results in the formation of a precursor layer with a graded compositional depth‐profile containing the crystalline phases In2Se3 and Cu2−xSe. Selenisation of the precursor layer homogenises the composition and forms chalcopyrite CIS. These CIS layers exhibit a dense microstructure with rough surface morphology, which is ascribed to a non‐optimal selenisation process. Solar cells with the structure ZnO: Al/i‐ZnO/CdS/CIS/Mo/glass have been processed from the selenised layers and have exhibited efficiencies of up to 4% under simulated AM1·5 illumination. Copyright © 2008 John Wiley & Sons, Ltd.
Expression profiles of MUC1, MUC2, and MUC4 mucins in human neoplasms and their relationship with biological behavior
Authors: Yonezawa Suguru , Goto Masamichi , Yamada Norishige , Higashi Michiyo , Nomoto Mitsuharu
Published: July 2008

Mucins are high molecular weight glycoproteins that play important roles in carcinogenesis or tumor invasion. To clarify the relationship of the expression patterns of mucins in human neoplasms with their biological behavior, we examined the expression profiles of MUC1, MUC2, and MUC4 mucins in various human neoplasms using immunohistochemistry and in situ hybridization, and compared them with clinicopathologic factors including outcome of the patients. MUC1 or MUC4 expression is related with the aggressive behavior of human neoplasms and a poor outcome of the patients. In contrast, MUC2 expression tends to be related with the indolent behavior of human neoplasms and a favorable outcome of the patients, although indolent pancreatobiliary neoplasms sometimes show invasive growth with MUC1 expression in the invasive areas. The expression of MUC2 mucin in indolent pancreatobiliary neoplasms coincided with expression of MUC2 mRNA. Our recent studies to clarify the MUC2 gene regulation mechanism disclosed that DNA methylation and histone modification in the 5′ flanking region of the MUC2 promoter may play an important role. Further studies of the epigenetics also in MUC1 and MUC4 gene expression may be needed to understand the relationship between the expression of mucins in human neoplasms with their biological behavior.
Glycosaminoglycan‐binding cytokines as tumor markers
Authors: Muramatsu Takashi , Muramatsu Hisako
Published: July 2008

A significant proportion of cytokines bind to glycosaminoglycans such as heparin. Glycosaminoglycans are involved in signaling, stabilization and/or storage of these cytokines. Typical examples of glycosaminoglycan‐binding cytokines are basic fibroblast growth factor (bFGF), interleukin‐8 (IL‐8), monocyte chemoattractant protein‐1 (MCP‐1), vascular endothelial growth factor (VEGF), VEGF‐C, hepatocyte growth factor (HGF), granulocyte colony‐stimulating factor (G‐CSF), midkine, and pleiotrophin. All are present in the tumor microenvironment and promote tumor growth, tumor invasion and/or tumor angiogenesis. Serum or plasma levels of glycosaminoglycan‐binding cytokines are frequently elevated in patients with various malignant tumors. High levels of these cytokines are usually correlated with the occurrence of metastasis and a poor prognosis. The mode of elevation of individual glycosaminoglycan‐binding cytokines in patients with malignant tumors is summarized here. Further studies, especially with multiple cytokines, are expected to make assays clinically useful for both early detection and prognostic prediction.
Application of a peptide‐based PF2D platform for quantitative proteomics in disease biomarker discovery
Authors: Lee Hyoung‐Joo , Kang Min‐Jeong , Lee Eun‐Young , Cho Sang Yun , Kim Hoguen , Paik Young‐Ki
Published: July 2008

A peptide‐based 2‐D liquid phase fractionation (PF2D) system was used in a quantitative proteomic analysis of hepatocellular carcinoma. 2‐D liquid maps of peptide specimens showed better resolution than those of proteins, leading to the identification of differentially expressed proteins. Peptide‐based PF2D gave well‐matched theoretical and experimental pI values and was proven to be a very efficient and versatile analytical tool for both large‐scale profiling and quantification of phosphoproteins in disease biomarker discovery.
Human sialidase as a cancer marker
Authors: Miyagi Taeko , Wada Tadashi , Yamaguchi Kazunori , Shiozaki Kazuhiro , Sato Ikuro , Kakugawa Yoichiro , Yamanami Hideaki , Fujiya Tsuneaki
Published: July 2008

Altered sialylation of cell surface glycoproteins and glycolipids is closely related to the malignant phenotype of cancer cells, including the metastatic potential and invasiveness. Many cancer‐related antigens in clinical use contain sialic acids at the terminal position of sugar chains in the molecules. To elucidate the molecular mechanism, we focused our investigation on sialidase, which catalyzes the removal of sialic acid residues from the glycoconjugates. Four types of human sialidases identified to date behave in different manners during carcinogenesis. One of the sialidases, found in the lysosomes, showed downregulation in cancers, promoting anchorage‐independent growth, and metastatic ability, while another, found in the plasma membrane, showed marked upregulation, causing apoptosis suppression. It was found that estimation of the mRNA levels of sialidases by real‐time PCR allowed discrimination of cancerous from noncancerous tissues and even determination of the pathological stage in some cancers. Immunohistochemistry of cancer tissues using the antibody against the plasma membrane sialidase was useful for clinical diagnosis. This paper briefly summarizes our findings of the altered sialidase expression in cancers and the possibility of their clinical application as cancer markers. Human sialidases are indeed related to malignancy and may be potential targets for cancer diagnosis and therapy.
Monitoring coping style moderates emotional reactions to genetic testing for hereditary nonpolyposis colorectal cancer: a longitudinal study
Authors: Shiloh S. , Koehly L. , Jenkins J. , Martin J. , Hadley D.
Published: July 2008

Objectives: The emotional effects of genetic testing for hereditary nonpolyposis colorectal cancer (HNPCC) provided within a counseling program were assessed among 253 individuals.

Methods: Assessments were scheduled at baseline before testing, and again after 6 and 12 months post‐test. Negative emotional reactions were evaluated using the Revised Impact of Event Scale and the Center for Epidemiological Studies‐Depression Scale. Monitoring coping style was assessed at baseline using the Miller Behavioral Style Scale.

Results: Mean reductions were indicated in distress and depression levels within the first 6 months after counseling and testing. High monitors were generally more distressed than low monitors, specifically if they had indeterminate or positive results.

Conclusions: Genetic counseling and testing for HNPCC do not result in long‐term distress for most people. Of the variables investigated, only time and coping style have main effects on emotional reactions, and the impacts of mutation status are moderated by coping style. Psychological interventions, aimed to alleviate adverse emotional effects, were suggested for certain participants, i.e. recipients of positive or indeterminate results who are high monitors. Copyright © 2008 John Wiley & Sons, Ltd.
The meaning of work and working life after cancer: an interview study
Authors: Rasmussen Dorte M. , Elverdam Beth
Published: July 2008

Background: Cancer survivors have diverse and complex patterns of return to work, but little attention has been given to individual experiences of returning to work.

Objectives: To analyse the meaning of work and working life for cancer survivors over time.

Methods: Participant observation was carried out at a cancer rehabilitation centre. A total of 23 participants were interviewed twice.

Results: Cancer survivors try to get back to work after treatment and try to re‐establish their former structure of everyday‐life that is seen as a normal and healthy existence. Work contributes to creating the individual as a social being, partaking in social relations with others. Work plays a role in establishing the individual's identity. It is difficult for many to resume work. When they are unable to work, they establish new activities in everyday‐life that give meaning to a life. In order to understand the cultural meaning of work in capitalist society, we incorporate the theoretical perspective of Max Weber.

Conclusion: Those who after cancer treatment are unable to work lose a part of their identity; they lose the personal challenge and satisfaction related to work. They are no longer part of the companionship related to work. Having had cancer means a disruption of the structure of everyday‐life that is taken for granted. Copyright © 2008 John Wiley & Sons, Ltd.
Psychosocial issues in genetic testing for familial adenomatous polyposis: a review of the literature
Authors: Douma K. F. L. , Aaronson N. K. , Vasen H. F. A. , Bleiker E. M. A.
Published: July 2008

Objectives: Familial adenomatous polyposis (FAP) is characterized by the development of multiple adenomas in the colon that can lead to colorectal cancer. Being a carrier for FAP is hypothesized to have a negative impact on psychosocial well‐being. This paper reviews the current literature on the psychosocial aspects of FAP.

Methods: Four literature databases were used to identify all papers published between 1986 and 2007 about psychosocial and behavioral issues in FAP related to genetic testing. The following topics were reviewed: uptake and psychosocial impact of genetic testing, endoscopic screening behavior and psychosocial well‐being in general.

Results: Seventeen papers were identified. Across studies, genetic test uptake varied between 62 and 97%. Two out of three studies showed clinical levels of anxiety and/or depression after genetic testing. A minority of individuals were not reassured by a negative test result, and intended to continue endoscopic surveillance. Well‐being (e.g. quality of life, family functioning) was found to be lower in some studies, while comparable to the general population in other studies. The studies had several shortcomings, such as mixed patient population (e.g. colorectal and breast cancer) and small sample sizes, and provided no information on other potentially important issues, such as psychosexual development.

Conclusions: Future studies should employ larger sample sizes and standardized measurements. Additionally, future studies should address the long‐term consequences of genetic testing for FAP, psychosexual development and consequences of FAP for the family as a whole. Copyright © 2008 John Wiley & Sons, Ltd.
Risk perception and cancer worries in families at increased risk of familial breast/ovarian cancer
Authors: Mellon Suzanne , Gold Robin , Janisse James , Cichon Michelle , Tainsky Michael A. , Simon Michael S. , Korczak Jeannette
Published: July 2008

While families at increased risk for familial breast/ovarian cancer continue to overestimate their cancer risk with increased cancer worries about the future, few studies have examined factors that affect inherited cancer risk perception and cancer worries in both survivors and unaffected female relatives. The purpose of this study was to examine variables that may affect cancer worries and risk perceptions from a family‐based perspective in a racially diverse, community‐based, random sample of 146 dyads consisting of adult female breast and/or ovarian cancer survivors and their unaffected female relatives (N=292). Results indicated that coping style, self‐efficacy, partner's income, family role relationship, and cancer risk perception were significant contributors to the survivors' and their unaffected relatives' cancer worries. Significant variables for perception of cancer risk for both survivors and relatives included income, race, family history of cancer, and cancer worries. Relatives had a higher perception of cancer risk, whereas survivors had more cancer worries. Additionally, the level of cancer worries reported by one member of the dyad was related to the amount of worries reported by the other. The results from this study underscore the importance of clinicians addressing concerns of both affected and unaffected members of families at increased risk of cancer to assist them in managing cancer worries and having realistic risk appraisals to make informed decisions about their own and their family's health surveillance options. Copyright © 2008 John Wiley & Sons, Ltd.
Genetic testing in familial melanoma: uptake and implications
Authors: de Snoo Femke A. , Riedijk Samantha R. , van Mil Anneke M. , Bergman Wilma , ter Huurne Jeanet A.C. , Timman Reinier , Bertina Wieke , Gruis Nelleke A. , Vasen Hans F.A. , van Haeringen Arie , Breuning Martijn H. , Tibben Aad
Published: July 2008

Objective: We report on the uptake and psychological impact of p16‐Leiden genetic testing to contribute to a greater understanding of counseling melanoma families.

Methods: Within a defined research setting, genetic counseling and testing were offered to members of p16‐Leiden‐positive melanoma pedigrees, at risk of carrying a gene defect associated with an increased risk of melanoma and pancreatic cancer.

Results: One hundred and eighty‐four individuals sought counseling, of which 141 (77%) opted for genetic testing. Uptake of genetic counseling and testing, and psychological motivation was evaluated in 94 (57%) individuals. Higher pre‐test risk of carrying the mutation and older age proved significantly predictive for counseling uptake. Age was predictive for test acceptance, whereas fearful test expectancies predicted test decline. Counselees had lower distress levels than those reported in other oncogenetic testing settings.

Conclusion: We are the first to report on genetic testing for familial melanoma. Following the first counseling session, we found a relatively high uptake rate for p16‐Leiden testing and no clinically worrisome levels of distress. Copyright © 2008 John Wiley & Sons, Ltd.
The transition from breast cancer ‘patient’ to ‘survivor’
Authors: Allen Jennifer D. , Savadatti Sanghamitra , Gurmankin Levy Andrea
Published: July 2008

Background: While much is now known about breast cancer survivors' long‐term health, quality of life, and psychological state, relatively little is known about the period immediately following completion of treatment, when women transition out of the role of breast cancer ‘patient’ to life as ‘survivor’.

Objective: To explore women's fears regarding risk of cancer recurrence, sense of loss of medical monitoring, and social support from health‐care providers and other patients, and the strategies they use to cope with these issues.

Method: Focus group interviews were conducted with women who had completed adjuvant chemotherapy or radiation for new stage I or II breast cancer in the prior 12 months. Interviews were audio‐taped, transcribed, and analyzed using a constant comparative analysis approach.

Results: Of 216 women identified as eligible, over half (155) were reached by telephone and invited to participate. Of those invited, 47 (30%) agreed. Findings suggest that while women acknowledge positive life changes as a result of the cancer experience, emotional and physical stresses are prevalent following the completion of treatment.

Conclusion: The period of time when women who have been treated for breast cancer transition to life without treatment presents numerous emotional and physical challenges. By illuminating patients' experience during this transition period, this study provides insights into the development of interventions to support women after treatment. Copyright © 2008 John Wiley & Sons, Ltd.
Behavioural functioning of retinoblastoma survivors
Authors: van Dijk J. , Oostrom K. J. , Imhof S. M. , Moll A. C. , Schouten‐van Meeteren A. Y. N. , Bezemer P. D. , Huisman J.
Published: July 2008

Objective: To assess behavioural problems in retinoblastoma (RB) survivors.

Methods: This population‐based cross‐sectional study included 148 RB survivors (8–35 years), registered in the Dutch national RB register. Survivors and parents were asked to fill in behavioural questionnaires. Prevalence rates were computed, based on both self‐reports and proxy reports. One‐sample T‐tests were applied to analyse differences compared with healthy reference samples. Multiple regression analyses were performed to identify predictors for behavioural problems within the RB sample.

Results: Between‐group differences varied across informants and across age groups. Parents reported significantly elevated total problem behaviour in 30% of their offspring (aged 8–17 years); this against 9% in adolescents (12–17 years) and 12% in adults (18–35 years) based on self‐report. Parental reports showed significantly elevated rates of (1) internalising problems in boys and (2) somatic complaints in both girls and boys. Self‐reports indicate significantly lowered levels of (1) externalising problems in adolescent and adult women and (2) thought problems in female adolescents and in adult men. Especially survivors who suffered hereditary RB, who had undergone more intensive treatment, and who came from a single‐parent family were identified to be at most behavioural risk.

Conclusion: Perception of severity and the nature of behavioural problems seem to differ between beholder, and to vary between age groups, if not between life stages. Health professionals should be aware that especially those who are confronted with hereditary RB and who subsequently undergo intensive treatment, and who grow up in broken families, run the risk of developing behavioural difficulties. Copyright © 2008 John Wiley & Sons, Ltd.
Breast cancer in young families: a qualitative interview study of fathers and their role and communication with their children following the diagnosis of maternal breast cancer
Authors: Forrest Gillian , Plumb Caroline , Ziebland Sue , Stein Alan
Published: July 2008

Objective: To explore father–child communication following the diagnosis of maternal breast cancer, examine disparities in their understandings of the impact of the illness, and identify gaps in their need for support and information.

Methods: The design is the qualitative interview study with thematic analysis. The interviews were home‐based with fathers and children in Oxfordshire, UK. The participants were 26 fathers whose partners had early breast cancer and 31 of their children aged between 6 and 18 years.

Results: Fathers described graphically their reaction to news of their partner's breast cancer and their attempts to provide support for their partners and maintain normal family life for their children. Fathers were keen to reassure and protect children but often said that they lacked sufficient information about breast cancer—especially side effects of treatments. Fathers sometimes did not recognise the extent of their children's distress and some interpreted their children's reactions as ‘bad behaviour’ or ‘rudeness’. Children were often acutely aware of the father's emotional state, and expressed a wish to protect him. Some fathers would have liked an opportunity to talk to a clinician directly about the children but did not want to claim clinical time for themselves or their children.

Conclusion: This study suggests that clinicians could improve their care of breast cancer patients by being more family‐centred. Fathers routinely need more information and preparation about the likely impact of the illness and its treatment (especially side effects) on the mother, and how children of different ages may react to the emotional strain. Clinicians need to be prepared to offer to talk to teenagers. Copyright © 2008 John Wiley & Sons, Ltd.
Antecedents of domain‐specific quality of life after colorectal cancer
Authors: Steginga Suzanne K. , Lynch Brigid M. , Hawkes Anna , Dunn Jeff , Aitken Joanne
Published: July 2008

Objective: The present study prospectively assessed the influence of medical, socio‐demographic, psychological, and lifestyle variables on physical, social/family, emotional, functional well‐being and colorectal cancer‐specific concerns in a population‐based sample of colorectal cancer survivors.

Methods: Participants (n=1822) were assessed at 6 and 24 months post‐diagnosis. Predictor variables assessed at 6 months included socio‐demographic and medical variables, symptoms/side‐effects, body mass index, physical activity, optimism, social support, and cancer threat appraisal. Quality of life (QOL) was assessed at 6 and 24 months post‐diagnosis using the Functional Assessment of Cancer Therapy ‐ Colorectal (FACT‐C).

Results: For each QOL subscale and for the overall FACT‐C scale, 6 month scores were the strongest predictor of QOL scores at 24 months post‐diagnosis (e.g. β=0.447, p < 0.001 for overall QOL). Socio‐demographic, medical, and psychosocial variables, but not lifestyle variables, differentially predicted domain specific QOL. Only cancer threat appraisal was associated with all five QOL domains.

Conclusion: Cancer threat appraisal presents as a potentially modifiable variable for interventions seeking to improve QOL. Symptom management and lifestyle strategies to ameliorate the effects of co‐morbidities, disease stage and troublesome symptoms such as faecal incontinence on QOL should also be included. Copyright © 2008 John Wiley & Sons, Ltd.
Cognitive and mood changes in men undergoing intermittent combined androgen blockade for non‐metastatic prostate cancer
Authors: Cherrier M.M. , Aubin S. , Higano C.S.
Published: July 2008

Purpose: Men with prostate‐specific antigen (PSA)‐only relapse of prostate cancer after primary therapy are generally fully functional and asymptomatic with a life expectancy of up to 10 or more years. Androgen deprivation therapy (ADT) is a common treatment option. This study examined mood and cognitive changes in otherwise healthy men with prostate cancer prior to, during and after ADT.

Experimental design: Twenty hormone naïve, eugonadal prostate cancer patients without evidence of metastases and with a rising PSA were treated with intermittent ADT consisting of 9 months of complete androgen blockade (CAB) achieved with combined leuprolide and flutamide followed by an ‘off treatment’ period. Cognitive function tests and mood measures were administered at baseline, after 3 and 9 months of ADT and after 3 months of no treatment. Twenty healthy control patients without prostate cancer range matched for age and education were tested at the same time intervals.

Results: ADT patients evidenced a significant decline in spatial reasoning, spatial abilities and working memory during treatment compared with baseline. No changes were noted for measures of verbal or spatial memory, selective attention or language. Significant changes in self‐rated mood such as increased depression, tension, anxiety, fatigue and irritability were evident during treatment compared with baseline for ADT patients. No significant changes in either cognitive tests or mood measures were noted for the healthy control group.

Conclusions: These findings, suggest that 9 months of combined androgen blockade may result in some adverse changes in cognition and mood. However, many but not all of these changes can return to baseline after cessation of ADT. Copyright © 2008 John Wiley & Sons, Ltd.
Some recommendations for the practitioner to improve the precision of experimentally determined protein folding rates and ϕ values
Authors: Ruczinski Ingo , Plaxco Kevin W.
Published: July 2008

The mechanism by which proteins fold from an initially random conformation into a functional, native structure remains a major unsolved question in molecular biology. Of particular interest to the protein folding community is the structure that the protein adopts in the folding transition state (the highest free energy state on the pathway from unfolded to folded), as that state forms the barrier that defines the folding pathway. Unfortunately, however, unlike those of the initial, unfolded state and the final, folded state of the protein, the structure in the transition state cannot be directly assessed via experiment. Instead, experimentalists infer the structure of the transition state, often by estimating changes in its free energy by measuring the effects of amino acid substitutions on folding and unfolding rates (Φ‐value analysis). In this article we show how to obtain more efficient estimates of these important quantities via improved experimental designs, and how to avoid common pitfalls in the analysis of kinetic data during the extraction of these parameters. Proteins 2009. © 2008 Wiley‐Liss, Inc.