bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased expression of the heterogeneous nuclear ribonucleoprotein K in pancreatic cancer and its association with the mutant p53
Authors: Zhou Renyuan , Shanas Reneé , Nelson Mark A. , Bhattacharyya Achyut , Shi Jiaqi 
Published: July 2009

AbstractThe heterogeneous nuclear ribonucleoprotein (hnRNP) K is an essential RNA and DNA binding protein involved in gene expression and signal transduction including DNA transcription, RNA splicing, RNA stability and translation. The role of hnRNP K in cancer is relatively understudied. However, several cellular functions strongly indicate that hnRNP K is involved in tumorigenesis. In this study, we investigated the altered protein expression and the subcellular distribution of the hnRNP K protein using tissue microarrays in pancreatic cancer. We showed an increased cytoplasmic hnRNP K in pancreatic cancer. This increase in hnRNP K protein occurs at the posttranscriptional level. We postulate that the cytoplasmic accumulation of hnRNP K will lead to silenced mRNA translation of tumor suppressor genes and thus contributes to pancreatic cancer development. We also demonstrated that knocking down of hnRNP K expression by siRNA inhibited pancreatic cancer cell growth and colony formation. hnRNP K was identified as a member of the p53/HDM2 pathway. Whether hnRNP K interacts with the mutant p53 is not known. Using two different pancreatic cancer cell lines, we can demonstrate that hnRNP K interacts with the mutant p53. The subcellular distribution and function of the mutant p53 and the interaction of hnRNP K/mutant p53 were affected by the Ras/MEK/ERK pathway, growth factors and the specific p53 mutations in pancreatic cancer cells. Since Kras is activated and p53 is mutated in most pancreatic cancers, these data unveiled an important new signaling pathway that linked by hnRNP K and mutant p53 in pancreatic cancer tumorigenesis.
Clinical whole‐body skin examination reduces the incidence of thick melanomas
Authors: Aitken Joanne F. , Elwood Mark , Baade Peter D. , Youl Philippa , English Dallas 
Published: July 2009

AbstractSurvival from melanoma is strongly related to tumour thickness, thus earlier diagnosis has the potential to reduce mortality from this disease. However, in the absence of conclusive evidence that clinical skin examination reduces mortality, evidence‐based assessments do not recommend population screening. We aimed to assess whether clinical whole‐body skin examination is associated with a reduced incidence of thick melanoma and also whether screening is associated with an increased incidence of thin lesions (possible overdiagnosis). We conducted a population‐based case‐control study of all Queensland residents aged 20–75 years with a histologically confirmed first primary invasive cutaneous melanoma diagnosed between January 2000 and December 2003. Telephone interviews were completed by 3,762 eligible cases (78.0%) and 3,824 eligible controls (50.4%). Whole‐body clinical skin examination in the three years before diagnosis was associated with a 14% lower risk of being diagnosed with a thick melanoma (>0.75 mm) (OR = 0.86, 95% CI = 0.75, 0.98). Risk decreased for melanomas of increasing thickness: the risk of being diagnosed with a melanoma 0.76–1.49 mm was reduced by 7% (OR = 0.93, 95% CI 0.79, 1.10), by 17% for melanomas 1.50–2.99 mm (OR = 0.83, 95% CI = 0.65, 1.05) and by 40% for melanomas ≥3 mm (OR = 0.60, 95% CI = 0.43, 0.83). Screening was associated with a 38% higher risk of being diagnosed with a thin invasive melanoma (≤0.75 mm) (OR = 1.38, 95% CI = 1.22, 1.56). This is the strongest evidence to date that whole‐body clinical skin examination reduces the incidence of thick melanoma. Because survival from melanoma is strongly related to tumour thickness, these results suggest that screening would reduce melanoma mortality.
Akt‐mediated regulation of NFκB and the essentialness of NFκB for the oncogenicity of PI3K and Akt
Authors: Bai Dong , Ueno Lynn , Vogt Peter K. 
Published: July 2009

AbstractThe serine/threonine kinase Akt (cellular homolog of murine thymoma virus akt8 oncogene), also known as PKB (protein kinase B), is activated by lipid products of phosphatidylinositol 3‐kinase (PI3K). Akt phosphorylates numerous protein targets that control cell survival, proliferation and motility. Previous studies suggest that Akt regulates transcriptional activity of the nuclear factor‐κB (NFκB) by inducing phosphorylation and subsequent degradation of inhibitor of κB (IκB). We show here that NFκB‐driven transcription increases in chicken embryonic fibroblasts (CEF) transformed by myristylated Akt (myrAkt). Accordingly, both a dominant negative mutant of Akt and Akt inhibitors repress NFκB‐dependent transcription. The degradation of the IκB protein is strongly enhanced in Akt‐transformed cells, and the loss of NFκB activity by introduction of a super‐repressor of NFκB, IκBSR, interferes with PI3K‐ and Akt‐induced oncogenic transformation of CEF. The phosphorylation of the p65 subunit of NFκB at serine 534 is also upregulated in Akt‐transformed cells. Our data suggest that the stimulation of NFκB by Akt is dependent on the phosphorylation of p65 at S534, mediated by IKK (IκB kinase) α and β. Akt phosphorylates IKKα on T23, and this phosphorylation event is a prerequisite for the phosphorylation of p65 at S534 by IKKα and β. Our results demonstrate two separate functions of the IKK complex in NFκB activation in cells with constitutive Akt activity: the phosphorylation and consequent degradation of IκB and the phosphorylation of p65. The data further support the conclusion that NFκB activity is essential for PI3K‐ and Akt‐induced oncogenic transformation. © 2009 UICC
Predictors of human papillomavirus persistence among women with equivocal or mildly abnormal cytology
Authors: Maucort‐Boulch Delphine , Plummer Martyn , Castle Philip E. , Demuth Franklin , Safaeian Mahboobeh , Wheeler Cosette M. , Schiffman Mark 
Published: July 2009

AbstractWe investigated short‐term persistence of human papillomavirus (HPV) infection among 2,408 women with low‐grade or equivocal cytological abnormalities followed for 24 months. Odds ratios (ORs) for persistence to the next 6‐month visit were estimated by a discrete time survival model. Prevalent HPV infections persisted longer in older women, but no association with age was found for incident HPV infections. Increased likelihood of persistence was found among current smokers of >20 cigarettes per day compared with smokers of ≤10 cigarettes per day (OR=1.43; 95% confidence interval [CI]: 1.02–2.01) and among current injectable contraceptive users (OR=1.15; 95% CI: 1.01–1.32). Persistence was more likely among infections with higher viral load (OR=2.05; 95% CI: 1.65–2.53) or with concurrent cytological abnormalities (OR=1.19; 95% CI: 1.03–1.39 and 1.29; 95% CI: 0.99–1.70 for ASCUS/LSIL and ASC‐H/HSIL, respectively). We conclude that new HPV infections in older women are not riskier by the metric of viral persistence than those in younger women. Other risk factors such as oral contraceptive use and multiparity that have been associated with cervical cancer or cervical intraepithelial neoplasia grade 3 were not associated with short‐term HPV persistence.
Tissue inhibitor of metalloproteinase‐1 protects MCF‐7 breast cancer cells from paclitaxel‐induced apoptosis by decreasing the stability of cyclin B1
Authors: Wang Ting , Lv Jing‐Huan , Zhang Xiong‐Fei , Li Chao‐Jun , Han Xiao , Sun Yu‐Jie 
Published: July 2009

AbstractPaclitaxel (PTX) is a very effective drug in treating tumors. It disturbs microtubule dynamics and impairs the transition of cells from metaphase to anaphase in mitosis, leading to cell death by apoptosis. However, the effectiveness of PTX in cancer chemotherapy is hampered by drug resistance in some patients. Tissue inhibitor of metalloproteinase‐1 (TIMP‐1) is well known to be capable of inhibiting apoptosis. Elevated tumor tissue TIMP‐1 levels have been significantly associated with a poor response to chemotherapy. We hypothesized that TIMP‐1 could reduce the sensitivity of breast cancer cells to PTX by inhibiting apoptosis. To test this hypothesis, we first examined the effects of TIMP‐1 on the apoptosis induced by PTX and investigated the effects of TIMP‐1 on the expression and stability of cyclin B1 that critically regulates the metaphase to anaphase transition during mitosis in MCF‐7 breast cancer cells. Our data demonstrate that TIMP‐1 could significantly decrease the sensitivity of MCF‐7 cells to PTX‐induced apoptosis, attenuate mitotic blockage in G2/M, and enhance the degradation of cyclin B1. To further investigate whether the inhibitory effect of TIMP‐1 on PTX‐induced apoptosis is mediated by lowering levels of cyclin B1, a cyclin B1‐expression plasmid was transfected into clone overexpressing TIMP‐1. The levels of PTX‐induced apoptosis were then analyzed. The data showed that the TIMP‐1‐based decrease in PTX‐induced apoptosis was reversed by cyclin B1. Our data indicate that TIMP‐1 can protect breast cancer cells from PTX‐induced apoptosis by decreasing the stability of cyclin B1.
Caveolin‐1 promotes resistance to chemotherapy‐induced apoptosis in Ewing's sarcoma cells by modulating PKCα phosphorylation
Authors: Tirado Oscar M. , MacCarthy Caitlin M. , Fatima Naheed , Villar Joaquín , Mateo‐Lozano Silvia , Notario and Vicente 
Published: July 2009

AbstractCaveolin‐1 (CAV1) has been implicated in the regulation of several signaling pathways and in oncogenesis. Previously, we identified CAV1 as a key determinant of the oncogenic phenotype and tumorigenic activity of cells from tumors of the Ewing's Sarcoma Family (ESFT). However, the possible CAV1 involvement in the chemotherapy resistance commonly presented by an ESFT subset has not been established to date. This report shows that CAV1 expression determines the sensitivity of ESFT cells to clinically relevant chemotherapeutic agents. Analyses of endogenous CAV1 levels in several ESFT cells and ectopic CAV1 expression into ESFT cells expressing low endogenous CAV1 showed that the higher the CAV1 levels, the greater their resistance to drug treatment. Moreover, results from antisense‐ and shRNA‐mediated gene expression knockdown and protein re‐expression experiments demonstrated that CAV1 increases the resistance of ESFT cells to doxorubicin (Dox)‐ and cisplatin (Cp)‐induced apoptosis by a mechanism involving the activating phosphorylation of PKCα. CAV1 knockdown in ESFT cells led to decreased phospho(Thr638)‐PKCα levels and a concomitant sensitization to apoptosis, which were reversed by CAV1 re‐expression. These results were recapitulated by PKCα knockdown and re‐expression in ESFT cells in which CAV1 was previously knocked down, thus demonstrating that phospho(Thr638)‐PKCα acts downstream of CAV1 to determine the sensitivity of ESFT cells to chemotherapeutic drugs. These data, along with the finding that CAV1 and phospho(Thr638)‐PKCα are co‐expressed in ∼45% of ESFT specimens tested, imply that targeting CAV1 and/or PKCα may allow the development of new molecular therapeutic strategies to improve the treatment outcome for patients with ESFT.
Urokinase plasminogen activator receptor is expressed in invasive cells in gastric carcinomas from high‐ and low‐risk countries
Authors: Alpízar‐Alpízar Warner , Nielsen Boye Schnack , Sierra Rafaela , Illemann Martin , Ramírez Jose A. , Arias Adriana , Durán Sundry , Skarstein Arne , Ovrebo Kjell , Lund Leif R. , Laerum Ole D. 
Published: July 2009

AbstractGastric cancer is the second cancer causing death worldwide. Both incidence and mortality rates vary according to geographical regions. The receptor for urokinase plasminogen activator (uPAR) is involved in extracellular matrix degradation by mediating cell surface associated plasminogen activation, and its presence on gastric cancer cells is linked to micro‐metastasis and poor prognosis. Immunohistochemical analyses of a set of 44 gastric cancer lesions from Costa Rica showed expression of uPAR in cancer cells in both intestinal subtype (14 of 27) and diffuse subtype (10 of 17). We compared the expression pattern of uPAR in gastric cancers from a high‐risk country (Costa Rica) with a low‐risk country (Norway). We found uPAR on gastric cancer cells in 24 of 44 cases (54%) from Costa Rica and in 13 of 23 cases (56%) from Norway. uPAR was seen in macrophages and neutrophils in all cases. We also examined the nonneoplastic mucosa and found that uPAR was more frequently seen in epithelial cells located at the luminal edge of the crypts in cases with Helicobacter pylori infection than in similar epithelial cells in noninfected mucosa (p = 0.033; χ2 = 4.54). In conclusion, the expression of uPAR in cancer cells in more than half of the gastric cancer cases suggests that their uPAR‐positivity do not contribute to explain the different mortality rates between the 2 countries, however, the actual prevalence of uPAR‐positive cancer cells in the gastric cancers may still provide prognostic information.
Sustained local drug delivery from a novel polymeric ring to inhibit intimal hyperplasia
Authors: Kanjickal Deenu , Lopina Stephanie , Evancho‐Chapman Mary M. , Schmidt Steven , Donovan Duane 
Published: July 2009

AbstractThe long‐term clinical success of autologous vein and synthetic vascular grafts are limited because of the development of anastomotic intimal hyperplasia (IH). We have previously published data suggesting that cyclosporine (CyA) may reduce the development of IH in a canine model (Hirko et al., J Vasc Surg 1993;17:877–887). However, systemic administration of CyA could create serious adverse effects. Therefore, it is our long‐term goal to test the hypothesis that the controlled local release of CyA from a polymeric vascular wrap would prevent the development of IH. To test this hypothesis, we developed a controlled release polymeric ring that could be placed around anastomotic sites to deliver therapeutic drugs locally. The ring is a composite polymeric device consisting of poly(DL‐lactide‐co‐glycolide) (PLGA) microspheres embedded in a poly(ethylene glycol) hydrogel. Several in vitro studies were conducted to evaluate the effects of different sterilization procedures on the properties of the device. It was determined that gamma sterilization was the preferred sterilization method of choice for this device. In vivo studies were conducted on a swine model to evaluate the biocompatibility of the ring. The histological findings of the ring implants at 2 and 4 weeks demonstrate the biocompatibility of this device. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Electrospun polyurethane vascular grafts: In vitro mechanical behavior and endothelial adhesion molecule expression
Authors: Grasl Christian , Bergmeister Helga , Stoiber Martin , Schima Heinrich , Weigel Guenter 
Published: July 2009

AbstractEngineered small diameter vascular grafts must closely match mechanical characteristics of native vessels and exhibit stimulus‐responsive bioactivity. In this study, mechanical homogeneity of electrospun small diameter polyurethane grafts as well as spontaneous attachment, proliferation, and adhesion molecule expression of endothelial cells (EC) in their presence was studied in vitro. Axial and circumferential tensile strengths were measured and found to be twofold higher in the circumferential direction. EC attachment was easily achieved without precoating the fiber matrix. Stimulation of EC with interleukin‐1β (IL‐1β) led to a statistically significant upregulation of the adhesion molecules E‐Selectin, ICAM‐1, and VCAM‐1. Quantification of adhesion molecule expression by means of energy‐dispersive X‐ray microanalysis revealed no differences in the stimulatory responses of EC cultured on electrospun polyurethane when compared with cells grown on tissue culture‐treated cover slips. Summarizing, highly uniform small diameter polyurethane grafts were fabricated and shown to allow spontaneous EC attachment. The synthetic graft surface neither impaired the endothelial response toward IL‐1β stimulation nor did it adversely affect the regulation of expression of endothelial adhesion molecules. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Synthesis of [3‐3H]20(S)‐protopanaxadiol
Authors: Meng Jian , Zhao Lizhi , Hu Youhong , Chen Xiaoyan , Zhong Dafang 
Published: July 2009

Abstract[3‐3H]20(S)‐Protopanaxadiol (PPD) was prepared via selective reduction of PPD dioxide with sodium borotritide in N,N‐dimethyl acetamide. A radiochemical yield of 22% was obtained. The radiochemical purity of the final product was 99% and the ratio of C‐3/C‐12 tritium labeling was 97:3. Copyright © 2009 John Wiley & Sons, Ltd.
Biofilm dispersal of community‐associated methicillin‐resistant Staphylococcus aureus on orthopedic implant material
Authors: Lauderdale Katherine J. , Malone Cheryl L. , Boles Blaise R. , Morcuende Jose , Horswill Alexander R. 
Published: July 2009

AbstractOrthopedic implant‐related bacterial infections are associated with high morbidity that may lead to limb amputation and exert significant financial burden on the healthcare system. Staphylococcus aureus is a dominant cause of these infections, and increased incidence of community‐associated methicillin‐resistant S. aureus (CA‐MRSA) is being reported. The ability of S. aureus to attach to the foreign body surface and develop a biofilm is an important determinant of resistance to antibiotic prophylaxis. To gain insight on CA‐MRSA biofilm properties, USA300 biofilm maturation and dispersal was examined, and these biofilms were found to exhibit pronounced, quorum‐sensing mediated dispersal from a glass surface. For comparison of biofilm maturation on different surface chemistries, USA300 biofilm growth was examined on glass, polycarbonate, and titanium, and minimal differences were apparent in thickness, total biomass, and substratum coverage. Importantly, USA300 biofilms grown on titanium possessed a functional dispersal mechanism, and the dispersed cells regained susceptibility to rifampicin and levofloxacin treatment. The titanium biofilms were also sensitive to proteinase K and DNaseI, suggesting the matrix is composed of proteinaceous material and extracellular DNA. These studies provide new insights on the properties of CA‐MRSA biofilms on implant materials, and indicate that quorum‐sensing dispersion could be an effective therapeutic strategy. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:55–61, 2010
Tip enhanced Raman spectroscopy on azobenzene thiol self‐assembled monolayers on Au(111)
Authors: Picardi Gennaro , Chaigneau Marc , Ossikovski Razvigor , Licitra Christophe , Delapierre Guillame 
Published: July 2009

AbstractTip enhanced Raman spectroscopy (TERS) and imaging experiments in tunnelling (gap) mode were performed on a 2 nm thick azobenzene thiol monolayer grafted on Au(111). A strong dependence on the tunnelling parameters, regulating the gold tip–gold surface gap distance, was observed for the intensity of the enhanced Raman signal. The influence of the incident light polarization is also discussed. Copyright © 2009 John Wiley & Sons, Ltd.
Spectroscopic investigation of modern pigments on purportedly medieval miniatures by the ‘Spanish Forger’
Authors: Burgio Lucia , Clark Robin J. H. , Hark Richard R. 
Published: July 2009

AbstractFive miniatures by the so‐called ‘Spanish Forger’ were acquired by the Victoria and Albert Museum in 2008. Believed to be authentic medieval miniatures until the mid‐twentieth century, they are now considered to have been painted around the end of the nineteenth and the beginning of the twentieth century. To investigate this attribution and to gather detailed knowledge about the materials used by the artist, a comprehensive pigment analysis by Raman microscopy and X‐ray fluorescence was carried out. Although traditional materials such as vermilion, carbon black, red lead, lead white and indigo were identified, many others (chrome yellow, Scheele's green, emerald green and ultramarine blue) are modern and synthetic pigments, a result which provides a firm scientific basis for stating that the miniatures are forgeries. Copyright © 2009 John Wiley & Sons, Ltd.
Silica‐based monolithic column with evaporative light scattering detector for HPLC analysis of bacosides and apigenin in Bacopa monnieri
Authors: Bhandari Pamita , Kumar Neeraj , Singh Bikram , Singh Virendra , Kaur Inderjeet 
Published: July 2009

AbstractA high performance liquid chromatographic method using a silica‐based monolithic column coupled with evaporative light scattering detector (HPLC–ELSD) was developed and validated for simultaneous quantification of bacosides (bacoside A, bacopaside I, bacoside A3, bacopaside II, bacopaside X, bacopasaponin C) and apigenin in Bacopa monnieri. The chromatographic resolution was achieved on a Chromolith RP‐18 (100×4.6 mm) column with acetonitrile/water (30:70) as mobile phase in isocratic elution at a flow rate of 0.7 mL/min. The drift tube temperature of the ELSD was set to 95°C, and the nitrogen flow rate was 2.0 SLM (standard liter per minute). The calibration curves revealed a good linear relationship (r2 >0.9988) within the test ranges. The detection limits (S/N = 3) and the quantification limits (S/N = 10) for the compounds were in the range of 0.54–6.06 and 1.61–18.78 μg/mL, respectively. Satisfactory average recovery was observed in the range of 95.8–99.0%. The method showed good reproducibility for the quantification of these compounds in B. monnieri with intra‐ and inter‐day precision of less than 0.69 and 0.67%, respectively. The validated method was successfully applied to quantify analytes in nine accessions of B. monnieri and thus provides a new basis for overall quality assessment of B. monnieri.
Separation of hydrophobic metabolites using monolithic silica column in high‐performance liquid chromatography and supercritical fluid chromatography
Authors: Bamba Takeshi , Fukusaki Eiichiro 
Published: July 2009

AbstractMonolithic silica columns have very low back‐pressures and offer several advantages over conventional columns packed with spherical particles, such as high separation efficiency and rapid analysis. In this review, we report the applicability of monolithic silica columns for the analysis of complex hydrophobic metabolites. We have used monolithic columns in HPLC and developed a separation technique for the high‐speed and high‐resolution analysis of the geometric analogs of natural polyprenols. We also used monolithic columns in supercritical fluid chromatography for the successful separation of the structural isomers of carotenoids after deciding the analytical conditions that were suitable for this separation and have developed a method for profiling biological samples containing complex matrices. We have proved that excellent resolution can be obtained by connecting a number of monolithic columns in series.