bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a functional variant in SPLUNC1 associated with nasopharyngeal carcinoma susceptibility among Malaysian Chinese
Authors: Yew Poh‐Yin , Mushiroda Taisei , Kiyotani Kazuma , Govindasamy Gopala Krishnan , Yap Lee‐Fah , Teo Soo‐Hwang , Lim Paul Vey‐Hong , Govindaraju Selvaratnam , Ratnavelu Kananathan , Sam Choon‐Kook , Yap Yoke‐Yeow , Khoo Alan Soo‐Beng , Pua Kin‐Choo , Nakamura Yusuke ,   The Malaysian NPC Study Group, Ng Ching‐Ching 
Published: December 2011

AbstractNasopharyngeal carcinoma (NPC) is a multifactorial and polygenic disease with high incidence in Asian countries. Epstein–Barr virus infection, environmental and genetic factors are believed to be involved in the tumorigenesis of NPC. The association of single nucleotide polymorphisms (SNPs) in LPLUNC1 and SPLUNC1 genes with NPC was investigated by performing a two‐stage case control association study in a Malaysian Chinese population. The initial screening consisted of 81 NPC patients and 147 healthy controls while the replication study consisted of 366 NPC patients and 340 healthy controls. The combined analysis showed that a SNP (rs2752903) of SPLUNC1 was significantly associated with the risk of NPC (combined P = 0.00032, odds ratio = 1.62, 95% confidence interval = 1.25–2.11). In the subsequent dense fine mapping of SPLUNC1 locus, 36 SNPs in strong linkage disequilibrium with rs2752903 (r2 ≥ 0.85) were associated with NPC susceptibility. Screening of these variants by electrophoretic mobility shift and luciferase reporter assays showed that rs1407019 located in intron 3 (r2 = 0.994 with rs2752903) caused allelic difference in the binding of specificity protein 1 (Sp1) transcription factor and affected luciferase activity. This SNP may consequently alter the expression of SPLUNC1 in the epithelial cells. In summary, our study suggested that rs1407019 in intronic enhancer of SPLUNC1 is associated with NPC susceptibility in which its A allele confers an increased risk of NPC in the Malaysian Chinese population. © 2011 Wiley Periodicals, Inc.
DNA repair genes XPC, XPG polymorphisms: Relation to the risk of colorectal carcinoma and therapeutic outcome with oxaliplatin‐based adjuvant chemotherapy
Authors: Liu Duo , Wu Hui‐zhe , Zhang Yi‐ning , Kang Hui , Sun Ming‐jun , Wang En‐hua , Yang Xiu‐li , Lian Min‐qiong , Yu Zhao‐jin , Zhao Lin , Olopade Olufunmilayo I. , Wei Min‐jie 
Published: December 2011

AbstractXeroderma pigmentosum complementation group C and G (XPC, XPG) play important roles in DNA damage repairing machinery. Genetic variations in the XPC and XPG may be associated with increased risk for colorectal carcinoma (CRC). In this study, we evaluated the relation between the XPC Lys939Gln, XPG Asp1104His polymorphisms, and CRC susceptibility in a population‐based case–control study, which included 1,028 CRC cases and 1,085 controls. Compared with the corresponding wild genotypes, we found that individuals with at least one copy of the XPC Lys939Gln (AC or CC genotype) and XPG Asp1104His (GC or CC genotype) had an increased risk for CRC. In addition, the variant genotypes of the XPC Lys939Gln AC/CC (P = 0.027) or XPG Asp1104His GC/CC (P = 0.003) reduced the elevation of preoperative carcinoembryonic antigen (CEA) level. Moreover a significantly longer progression‐free survival (PFS) after Oxaliplatin‐based adjuvant chemotherapy was observed in patients with XPG Asp1104His wide‐type GG genotype (n = 432, Log‐rank test: P = 0.033). Cox proportional hazards analyses demonstrated that variant genotypes of XPG Asp1104His [hazard ratio (HR) = 1.692, 95% confidence interval (95%CI): 1.202–2.383, P = 0.003] as well as pathology grade (HR = 2.545, 95%CI: 2.139–3.030, P < 0.001), and lymph node metastases (HR = 1.851, 95%CI: 1.306–2.625, P < 0.001) were predictive of shorter PFS for the CRC patients with Oxaliplatin‐based adjuvant chemotherapy. In conclusion, the current data suggested that XPC Lys939Gln and XPG Asp1104His polymorphisms might contribute to the identification of patients with increased risk for CRC. © 2011 Wiley Periodicals, Inc.
Expression of microRNAs, miR‐21, miR‐31, miR‐122, miR‐145, miR‐146a, miR‐200c, miR‐221, miR‐222, and miR‐223 in patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma and its prognostic significance
Authors: Karakatsanis Andreas , Papaconstantinou Ioannis , Gazouli Maria , Lyberopoulou Anna , Polymeneas George , Voros Dionysios 
Published: December 2011

AbstractMicroRNAs are a class of non‐coding molecules found to regulate a variety of cellular functions in health and disease. Dysregulation of microRNAs is involved in liver disease, especially hepatocarcinogenesis. Since primary hepatic malignancies are typically characterized by late diagnosis, frequent recurrence, and poor response to adjuvant therapy, there is a need for the discovery of novel biomarkers in order to achieve earlier diagnosis, predict tumor aggressiveness and response to adjuvant therapy. The purpose of this study is to evaluate the expression of certain microRNAs (miR‐21, ‐31, ‐122, ‐145, ‐146a, ‐ 200c, ‐221, ‐222 and ‐223) in patients with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), as well as to assess their prognostic significance. Micro‐RNA expression was assessed by reverse transcription and real‐time PCR (RT‐PCR). Clinicopathological data and survival rates were retrieved and analyzed. According to our results, miR‐21, miR‐31, miR‐122, miR‐221, miR‐222 were significantly up‐regulated in HCC tissues, whereas miR‐145, miR‐146a, miR‐200c, and miR‐223 were found to be down‐regulated. Concerning ICC samples, miR‐21, miR‐31, and miR‐223 were found to be over‐expressed, whereas miR‐122, miR‐145, miR‐200c, miR‐221, and miR‐222 were down‐regulated. Additionally, expression of miR‐21, miR‐31, miR‐122, and miR‐221 in HCC correlated with cirrhosis, while miR‐21 and miR‐221 associated with tumor stage and poor prognosis. In ICC tissues, miR‐21, miR‐31, and miR‐223 were found to be over‐expressed, but no correlation with clinicopathological features was found. © 2011 Wiley Periodicals, Inc.
Functional polymorphism rs7072793 C > T affect individual susceptibility to breast cancer by modulating CD25 transcription activity
Authors: Li Hongbin , Zhou Hongfeng , Zhang Qingyuan , Zhao Shu , Zhang Yue , Wang Yan , Liu Jinglei , Song Ying , Yu Xiaojin , Yu Yan 
Published: December 2011

AbstractSubstantial evidence has demonstrated immune defects in breast cancer patients. They have decreased numbers of peripheral blood lymphocytes, but higher numbers of functionally suppressive CD4+CD25+ Treg in both peripheral blood and tumor microenvironment. Constitutive high expression of CD25 is a pivotal characteristic of natural Treg cells. This study aims at investigating if CD25 variability affects breast carcinogenesis. Two polymorphisms (rs7072793 C > T, rs3118470 C > T) in the promoter of CD25 were selected and analyzed by a multiple independent case‐control study to assess the association between CD25 genotypes and breast cancer risk. Genotyping a total of 1110 patients and 1060 healthy controls in Chinese populations showed that rs7072793 CT genotype had an odd ratio of 1.49 (95% confidence interval, 1.23–1.89) for developing breast cancer compared with CC genotype, the rs7072793 TT carriers had a further increased risk of breast cancer (OR = 2.11; 95% CI = 1.66–2.87). Furthermore, our transient transfection which focused on reporter gene expression modulated by CD25 promoter demonstrated that the presence of an rs7072793 T allele led to greater transcriptional activity than the C allele. Similarly, rs13347 T carriers were shown to have larger proportion of CD4+CD25+ Tregs in the PBMCs than C carriers in the flow cytometry analysis. However, no significant differences were found in genotype frequencies at rs3118470 C > T site between cases and controls. Our findings suggest that rs7072793 C > T genetic variation in CD25 genes may be genetic modifier for developing breast cancer. © 2011 Wiley Periodicals, Inc.
SWIFT‐CEST: A new MRI method to overcome T2 shortening caused by PARACEST contrast agents
Authors: Soesbe Todd C. , Togao Osamu , Takahashi Masaya , Sherry A. Dean 
Published: December 2011

AbstractThe exchange of water molecules between the inner sphere of a paramagnetic chemical exchange saturation transfer (PARACEST) contrast agent and bulk water can shorten the bulk water T2 through the T2‐exchange (T2ex) mechanism. The line‐broadening T2ex effect is proportional to the agent concentration, the chemical shift of the exchanging water molecule, and is highly dependent on the water molecule exchange rate. A significant T2ex contribution to the bulk water linewidth can make the regions of agent uptake appear dark when imaging with conventional sequences like gradient‐echo and fast spin‐echo. The minimum echo times for these sequences (1–10 ms) are not fast enough to capture signal from the regions of shortened T2. This makes “Off” (saturation at −Δω) minus “On” (saturation at +Δω) imaging of PARACEST agents difficult, because the regions of uptake are dark in both images. It is shown here that the loss of bulk water signal due to T2ex can be reclaimed using the ultrashort echo times (<10 μs) achieved with the sweep imaging with Fourier transform pulse sequence. Modification of the sweep imaging with Fourier transform sequence for PARACEST imaging is first discussed, followed by parameter optimization using in vitro experiments. In vivo PARACEST studies comparing fast spin‐echo to sweep imaging with Fourier transform were performed using EuDOTA‐(gly) uptake in healthy mouse kidneys. The results show that the negative contrast caused by T2ex can be overcome using the ultrashort echo time achieved with sweep imaging with Fourier transform, thereby enabling fast and sensitive in vivo PARACEST imaging. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.
Relating fracture behavior to spherulite size in conrolled‐rheology polypropylenes
Authors: Salazar A. , Rico A. , Rodríguez S. , Navarro J.M. , Rodríguez J. 
Published: December 2011

AbstractThe influence of the spherulite size and distribution on the fracture toughness and Izod impact strength at different temperatures of controlled‐rheology polypropylenes with 0, 154, 402, and 546 ppm of peroxide has been evaluated. As the peroxide content increased, the average spherulite size was enhanced and the distribution width reduced. The fracture toughness and the Izod impact strength were lowered with the peroxide content due to the diminution of the amorphous interconnections among the crystalline regions. Porosity seems to control the fracture behavior for the materials with the highest peroxide content. Besides, a considerable loss of ductility was observed ahead of the stable crack growth zone. Below the glass transition temperature, the impact strength underwent a sudden drop with the temperature, more remarkable as the molecular was higher. The main mechanism of deformation and failure consisted on the formation of crazes, stretch out, and a final collapse through the interspherulitic zones. POLYM. ENG. SCI., 2011. © 2011 Society of Plastics Engineers
Fabrication of honeycomb‐structured porous films from poly(3‐hydroxybutyrate) and poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) via the breath figures method
Authors: Huh Mongyoung , Jung Min‐Hye , Park Young Soo , Kang Tae‐Beom , Nah Changwoon , Russell Robert A. , Holden Peter J. , Yun Seok Il 
Published: December 2011

AbstractFormation of porous films from poly(3‐hydroxybutyrate) (PHB) and poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) (PHBV) using the breath figures (BF) method was investigated by evaporating solutions in chloroform in humid air and examining film structure using optical and scanning electron microscopy (SEM). BF films were successfully fabricated from PHB (Mw = 486,000 g/mol) and displayed hexagonal arrays of pores, which varied in diameter (D = 7–2 μm) with solution concentrations (0.5–2.00%). SEM of fractured films also showed subsurface closed nano‐pores (D = 500–700 nm). BF films cast from PHBV (5% HV) formed arrays with smaller pores and apparent surface defects. Differential scanning calorimetry showed that porous PHB and PHBV films produced using the BF method were more crystalline than nonporous solvent cast films of PHB and PHBV. POLYM. ENG. SCI., 2011. © 2011 Society of Plastics Engineers
Origin and influence of water‐induced chain relaxation phenomena in chitosan biopolymers
Authors: Kobaisi Mohammad Al , Murugaraj Pandiyan , Mainwaring David E. 
Published: December 2011

AbstractChain dynamics, probed by dielectric spectroscopy, provide a route to further understanding of the molecular interactions induced by hydration, degree of crosslinking, and microstructural changes occurring on swelling of biopolymers such as chitosan, which is becoming a focus for biomedical engineering and therapeutic delivery. The basis of the β‐wet relaxation peak is established as segmental chain relaxation between chitosan water bridges and related to its hysteresis induced by microstructural changes during wetting and dewetting cycles. Linear expansion probes the hysteresis arising from bridging water interactions during the hydration–dehydration paths which is also shown in the resultant ionic conductivity. β‐wet relaxation and ionic conductivity exhibit identical hysteresis behavior with both degrees of chemical crosslinking and water contents. X‐ray diffraction shows that the degree of crosslinking and hydration also influences the degree of disorder of the polymer chains changing both the crystalline phase fraction and lattice dimensions. These molecular interactions provide power law behavior between β‐wet relaxation dynamics and ionic mobility over five orders of magnitude for all degrees of chemical crosslinking and water bridging which is independent of the significant hysteresis in these properties indicative of scaling behavior within the noncrystalline gel phase. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2012
Modulation of cell responses by creating surface submicron topography and amine functionalities
Authors: Chen Jian‐Je , Ho Quoc‐Phong , Wang Meng‐Jiy 
Published: December 2011

AbstractThe incorporation of biological function into synthetic polymers provides particular potential for advances in studying the complex interactions between biomolecules and materials. We developed a simple method to create polymer with submicron features on surface of polystyrene‐co‐maleic anhydride (PSMAA) using a combination of phase‐separation and spin coating method. The nanostructured PSMAA which was rarely utilized as biomaterials was further functionalized by doping with dopamine or by treating with nitrogen containing plasma. This study demonstrated a straightforward method that the creation of topographical cues alone improves the biocompatibility of PSMAA thin film. The cell proliferation increased more significantly to ∼1.8‐ and 2.5‐fold on dopamine blended and N2/H2 plasma treated PSMAA films when compared to that on the flat sample, respectively. The overall results showed that the integration of microenvironment and chemical functionalities into materials provide promising effects for promoting mammalian cell growth. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2012
"The quest for biomarkers": Are we on the right technical track?
Authors: Boschetti Egisto , Chung Maxey C. M. , Righetti Pier Giorgio 
Published: December 2011

AbstractThe discovery phase of biomarkers of diagnostic or therapeutic interest started a decade ago with the very rapid development of proteomic investigations. In spite of the development of innovative technologies and multiple approaches, the "harvest" is still modest. Various reasons justified the encountered difficulties and most of them have been circumvented by specific sample treatments or dedicated analytical approaches. Nevertheless, the situation of very modest biomarker discovery level did not change much. This review intends to specifically analyze the main approaches used for biomarker discovery phase and evaluate related advantages and disadvantages. Thus, preliminary sample treatments such as fractionation, depletion and reduction of dynamic concentration range will critically be discussed and then the main differential expression investigation methods analyzed. Combinations of technologies are also discussed along with possible proposals to federate associations of complementary technologies for better chances of success.
Functional protease profiling for diagnosis of malignant disease
Authors: Findeisen Peter , Neumaier Michael 
Published: December 2011

AbstractClinical proteomic profiling by mass spectrometry (MS) aims at uncovering specific alterations within mass profiles of clinical specimens that are of diagnostic value for the detection and classification of various diseases including cancer. However, despite substantial progress in the field, the clinical proteomic profiling approaches have not matured into routine diagnostic applications so far. Their limitations are mainly related to high‐abundance proteins and their complex processing by a multitude of endogenous proteases thus making rigorous standardization difficult. MS is biased towards the detection of low‐molecular‐weight peptides. Specifically, in serum specimens, the particular fragments of proteolytically degraded proteins are amenable to MS analysis. Proteases are known to be involved in tumour progression and tumour‐specific proteases are released into the blood stream presumably as a result of invasive progression and metastasis. Thus, the determination of protease activity in clinical specimens from patients with malignant disease can offer diagnostic and also therapeutic options. The identification of specific substrates for tumour proteases in complex biological samples is challenging, but proteomic screens for proteases/substrate interactions are currently experiencing impressive progress. Such proteomic screens include peptide‐based libraries, differential isotope labelling in combination with MS, quantitative degradomic analysis of proteolytically generated neo‐N‐termini, monitoring the degradation of exogenous reporter peptides with MS, and activity‐based protein profiling. In the present article, we summarize and discuss the current status of proteomic techniques to identify tumour‐specific protease‐substrate interactions for functional protease profiling. Thereby, we focus on the potential diagnostic use of the respective approaches.
High mobility group protein AT‐hook 1 (HMGA1) is associated with the development of androgen independence in prostate cancer cells
Authors: Takeuchi Ichiro , Takaha Natsuki , Nakamura Terukazu , Hongo Fumiya , Mikami Kazuya , Kamoi Kazumi , Okihara Koji , Kawauchi Akihiro , Miki Tsuneharu 
Published: December 2011

AbstractBACKGROUNDWe previously reported that the level of high mobility group protein AT‐hook 1 (HMGA1) is low in androgen‐dependent prostate cancer (PCa) cells (LNCaP), but is high in androgen‐independent PCa cells (DU145 and PC‐3) and that HMGA1 is a strong candidate gene playing a potential role in the progression of PCa. These findings have prompted us to evaluate the effect of HMGA1 on developing androgen independency, which is associated with the progression of PCa.METHODSExpression of HMGA1 in PCa cells and mouse tissues was examined by Western blot. In order to examine the effect of HMGA1 on cell growth under androgen‐deprived condition, we transfected HMGA1 into LNCaP cells, and siRNA into both DU145 and PC‐3 cells, respectively.RESULTSAndrogen‐deprivation induced an increase in the level of HMGA1 in LNCaP cells in vitro and in vivo, but did not in normal prostate tissue. Overexpression of HMGA1 maintained the cell growth of LNCaP under androgen‐deprived condition. Furthermore, knockdown of HMGA1 suppressed the cell growth of DU145 and PC‐3.CONCLUSIONSThese data suggest that elevated expression of HMGA1 is associated with the transition of PCa cells from androgen‐sensitive to androgen‐independent growth and plays a role in the cell growth of androgen‐independent PCa cells. Prostate 72:1124–1132, 2012. © 2011 Wiley Periodicals, Inc.
Androgen receptor overexpression alters binding dynamics of the receptor to chromatin and chromatin structure
Authors: Urbanucci Alfonso , Marttila Saara , Jänne Olli A. , Visakorpi Tapio 
Published: December 2011

AbstractBACKGROUNDCastration‐resistant prostate cancers (CRPCs) overexpress often androgen receptor (AR). Here, we investigated the effect of AR overexpression on the dynamics of AR loading and RNA polymerase II (RNA Pol II) recruitment to chromatin. Acetylation of histone 3 (AcH3) on lysines 9 and 14 (K9 and K14) was also studied.METHODSWe used an LNCaP‐based AR overexpression cell line model that includes a control line and two sublines, LNCaP‐ARmo and LNCaP‐ARhi, which overexpress AR twofold to threefold and fourfold to fivefold, respectively. Cells were exposed to 1 or 100 nM of dihydrotestosterone (DHT). Chromatin immunoprecipitation (ChIP) on the promoters and enhancers of prostate specific antigen (PSA) and transmembrane protease, serine 2 (TMPRSS2) genes was performed. qRT‐PCR was used to measure the levels of PSA and TMPRSS2 transcripts.RESULTSUpon stimulation with 1 nM DHT, AR and RNA Pol II were recruited onto PSA and TMPRSS2 enhancer regions to a greater extent (P < 0.05) in AR‐overexpressing cells compared to control cells. The difference in AR loading between the control and AR‐overexpressing cells was abolished by a higher DHT concentration. The ratio of AcH3/H3 was increased in AR‐overexpressing cells. The induction of transcription of PSA and TMPRSS2 occurred earlier in the AR‐overexpressing cells.CONCLUSIONSOur findings suggest that the levels of AR potentiate the recruitment of the AR, as well as components of the basic transcription machinery, to chromatin and affect the acetylation of histones in the presence of low levels of androgens. These changes result in enhanced gene transcription of AR target genes. Prostate 72:1223–1232, 2012. © 2011 Wiley Periodicals, Inc.
TP53INP1 as new therapeutic target in castration‐resistant prostate cancer
Authors: Giusiano Sophie , Baylot Virginie , Andrieu Claudia , Fazli Ladan , Gleave Martin , Iovanna Juan Lucio , Taranger‐Charpin Colette , Garcia Stéphane , Rocchi Palma 
Published: December 2011

AbstractBACKGROUNDProstate cancer (PC) is one of the most common malignancies in industrialized countries, and the second leading cause of cancer‐related death in the United States. We recently showed that over‐expression of tumor protein 53‐induced nuclear protein 1 (TP53INP1), a cell stress response protein, is a worse prognostic factor in PC, particularly predictive of biological cancer relapse. Moreover, treatment of castration‐sensitive (CS) LNCaP tumor cells with a TP53INP1 antisense oligonucleotide (TP53INP1 ASO) inhibits proliferation and induces apoptosis. The aim of this study was to investigate variations of TP53INP1 expression in PC during androgen withdrawal therapy and in castration‐resistant prostate cancer (CRPC).METHODSQuantitative measurements of immunohistochemical expression of TP53INP1 using high‐throughput densitometry, assessed on digitized microscopic tissue micro‐array images were correlated with hormone therapy (HT) status in human PC. Northern blot analysis of TP53INP1 after castration was performed in LNCaP xenograft. Treatment of CR C4‐2 tumor cells in vitro with TP53INP1 ASO was analyzed. We also analyzed the effect of TP53INP1 ASO treatment in vivo on tumor xenograft growth.RESULTSTP53INP1 protein expression decreases during HT and increases after HT in human CRPC. TP53INP1 mRNA increases significantly in CR tumors of LNCaP xenograft. Moreover, treatment of CR C4‐2 cells with TP53INP1 ASO downregulates TP53INP1 protein level, inhibits proliferation, and induces apoptosis. Finally, in vivo, TP53INP1 ASO treatment significantly inhibits the tumoral progression of CR C4‐2 xenograft and enhances docetaxel cytotoxicity.CONCLUSIONSThese results suggest that TP53INP1 could be considered as a relevant‐specific target for molecular therapy of CRPC. Prostate 72:1286–1294, 2012. © 2011 Wiley Periodicals, Inc.