bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term aspirin use and the risk of total, high‐grade, regionally advanced and lethal prostate cancer in a prospective cohort of health professionals, 1988–2006
Authors: Dhillon Preet K. , Kenfield Stacey A. , Stampfer Meir J. , Giovannucci Edward L. 
Published: December 2010

AbstractExperimental studies suggest a role for aspirin in the chemoprevention of prostate cancer and epidemiological evidence supports a modest inverse association between regular aspirin use and prostate cancer risk, especially for advanced disease. In a prospective cohort study of 51,529 health professionals aged 40–75 years at baseline, we evaluated long‐term aspirin use and the incidence of total, high‐grade (Gleason 8‐10, n = 488), regionally advanced (T3b‐T4 or N1, n = 228) and lethal prostate cancer (M1, bony metastases or prostate cancer death, n = 580) from 1988–2006. We used Cox proportional hazards regression to evaluate risk associated with frequency (days/week), quantity (tablets/week), recency and duration of aspirin use after multivariable adjustment for confounders and other predictors of prostate cancer risk. A total of 4,858 men were diagnosed with prostate cancer during the 18‐year study period. Men taking ≥ 2 adult‐strength aspirin tablets a week had a 10% lower risk of prostate cancer (p‐for‐trend = 0.02). For regionally advanced cancer, we observed no significant associations with aspirin use. For high‐grade and lethal disease, men taking ≥ 6 adult‐strength tablets/week experienced similar reductions in risk hazard ratio [HR = 0.72 (95% confidence intervals [CI]: 0.54, 0.96) and HR = 0.71 (95% CI: 0.50, 1.00)]. Analytical approaches to address bias from more frequent prostate‐specific antigen screening among aspirin users did not yield different conclusions. We observed reductions in the risk of high‐grade and lethal prostate cancer associated with higher doses of aspirin, but not with greater frequency or duration, in a large, prospective cohort of health professionals. Our data support earlier observations of modest inverse associations with advanced prostate cancer.
Detection of circulating tumor cells as a prognostic factor in patients undergoing radical surgery for non‐small‐cell lung carcinoma: comparison of the efficacy of the CellSearch Assay™ and the isolation by size of epithelial tumor cell method
Authors: Hofman Véronique , Ilie Marius I. , Long Elodie , Selva Eric , Bonnetaud Christelle , Molina Thierry , Vénissac Nicolas , Mouroux Jérôme , Vielh Philippe , Hofman Paul 
Published: December 2010

AbstractComparison of the efficacy of different enrichment methods for detection of circulating tumor cells (CTCs) before radical surgery is lacking in non‐small‐cell lung carcinoma (NSCLC) patients. Detection and enumeration of CTCs in 210 consecutive patients undergoing radical surgery for NSCLC were evaluated with the CellSearch Assay™ (CS), using the CellSearch Epithelial Cell Kit, and by the isolation by size of epithelial tumor (ISET) method, using double immunolabeling with anti‐cytokeratin and anti‐vimentin antibodies. CTCs were detected in 144 of 210 (69%) patients using CS and/or ISET and in 104 of 210 (50%) and 82 of 210 (39%) patients using ISET and CS, respectively. Using ISET, 23 of 210 (11%) patients had vimentin‐positive cells with cytological criteria of malignancy. Disease‐free survival (DFS) was worse for patients with CTCs compared to patients without CTCs detected by CS alone (p < 0.0001; log rank = 30.59) or by ISET alone (p < 0.0001; log rank = 33.07). The presence of CTCs detected by both CS and ISET correlated even better with shorter DFS at a univariate (p < 0.0001; log rank = 42.15) and multivariate level (HR, 1.235; 95% CI, 1.056–1.482; p < 0.001). CS and ISET are complementary methods for detection of CTCs in preoperative radical surgery for NSCLC. CTC detection in resectable NSCLC patients using CS and/or ISET could be a prognostic biomarker of great interest and may open up new avenues into improved therapeutic strategies for lung carcinoma patients.
Association of low‐risk MSH3 and MSH2 variant alleles with Lynch syndrome: Probability of synergistic effects
Authors: Duraturo Francesca , Liccardo Raffaella , Cavallo Angela , Rosa Marina De , Grosso Michela , Izzo Paola 
Published: December 2010

AbstractMutations in the MLH1 and MSH2 genes account for a majority of cases of families with Lynch Syndrome. Germ‐line mutations in MSH6, PMS2 and MLH3 are responsible for disease in a minority of cases, usually associated with milder and variable phenotypes. No germ‐line mutations in MSH3 have so far been associated with Lynch Syndrome, although it is known that impaired MSH3 activity leads to a partial defect in mismatch repair (MMR), with low levels of microsatellite instability at the loci with dinucleotide repeats in colorectal cancer (CRC), thus suggesting a role for MSH3 in carcinogenesis. To determine a possible role of MSH3 as predisposing to CRC in Lynch syndrome, we screened MSH3 for germ‐line mutations in 79 unrelated Lynch patients who were negative for pathogenetic mutations in MLH1, MSH2 and MSH6. We found 13 mutant alleles, including silent, missense and intronic variants. These variants were identified through denaturing high performance liquid chromatography and subsequent DNA sequencing. In one Lynch family, the index case with early‐onset colon cancer was a carrier of a polymorphism in the MSH2 gene and two variants in the MSH3 gene. These variants were associated with the disease in the family, thus suggesting the involvement of MSH3 in colon tumour progression. We hypothesise a model in which variants of the MSH3 gene behave as low‐risk alleles that contribute to the risk of colon cancer in Lynch families, mostly with other low‐risk alleles of MMR genes.
Carcinogen‐induced squamous papillomas and oncogenic progression in the absence of the SSeCKS/AKAP12 metastasis suppressor correlate with FAK upregulation
Authors: Akakura Shin , Bouchard Rene , Bshara Wiam , Morrison Carl , Gelman Irwin H. 
Published: December 2010

AbstractThe ability of SSeCKS/Gravin/AKAP12 (SSeCKS) to negatively regulate cell cycle progression is thought to relate to its spatiotemporal scaffolding activity for key signaling molecules such as protein kinase A and C, calmodulin and cyclins. SSeCKS is downregulated upon progression to malignancy in many cancer types, including melanoma and nonmelanoma skin cancer. The forced re‐expression of SSeCKS is especially potent in suppressing metastasis through the inhibition of VEGF‐mediated neovascularization. We have previously shown that SSeCKS‐null (KO) mice exhibit hyperplasia and focal dysplasia in the prostate marked by activated Akt. To address whether KO mice exhibit increased skin carcinogenesis, WT and KO C57BL/6 mice were treated topically with 12‐O‐tetradecanoylphorbol‐13‐acetate and 7,12‐dimethylbenzanthracene. Compared to WT mice, KO mice developed squamous papillomas more rapidly and in greater numbers and also exhibited significantly increased progression to squamous cell carcinoma. Untreated KO epidermal layers were thicker than those in age‐matched WT mice and exhibited significantly increased levels of FAK and phospho‐ERK1/2, known mediators of carcinogen‐induced squamous papilloma progression to carcinoma. Compared to protein levels in WT mouse embryo fibroblasts (MEF), SSeCKS levels were increased in FAK‐null cells, whereas FAK levels were increased in SSeCKS‐null cells. RNAi studies in WT MEF cells suggest that SSeCKS and FAK attenuate each other's expression. Our study implicates a role for SSeCKS in preventing of skin cancer progression possibly through negatively regulating FAK expression.
Phosphatidylinositol‐3′‐kinase/AKT signaling is essential in synovial sarcoma
Authors: Friedrichs Nicolaus , Trautmann Marcel , Endl Elmar , Sievers Elisabeth , Kindler Dagmar , Wurst Peter , Czerwitzki Jacqueline , Steiner Susanne , Renner Marcus , Penzel Roland , Koch Arend , Larsson Olle , Tanaka Shinya , Kawai Akira , Schirmacher Peter , Mechtersheimer Gunhild , Wardelmann Eva , Buettner Reinhard , Hartmann Wolfgang 
Published: December 2010

AbstractSynovial sarcomas account for 5–10% of all malignant soft tissue tumors. They have been shown to express different membranous growth factor receptors, many of them signaling via intracellular kinase cascades. In our study, the functional role of PI3K/AKT signals in synovial sarcoma is analyzed with regard to tumor biology and therapeutic applicability. Immunohistochemical stainings of (Ser473)‐phosphorylated (p)‐AKT, its targets p‐(Ser9)‐GSK‐3β and p‐(Ser2448)‐mTOR and the cell cycle regulators Cyclin D1 and p27KIP1 were performed in 36 synovial sarcomas. The PIK3CA gene was screened for mutations. In vitro, four synovial sarcoma cell lines were treated with the PI3K inhibitor LY294002. Phosphorylation of AKT, GSK‐3β and mTOR was assessed, and cellular proliferation and apoptosis were analyzed to functionally characterize the effects of PI3K inhibition. Finally, coincubations of LY294002 with cytotoxic drugs were performed. Most tumors showed significant expression levels of p‐AKT, p‐GSK‐3β and p‐mTOR, indicating activation of the PI3K/AKT signaling cascade in synovial sarcomas; Cyclin D1 and p27KIP1 were differentially expressed. Mutations in the PIK3CA gene could be excluded. In vitro, PI3K inhibition diminished synovial sarcoma cell growth accompanied by reduced phosphorylation of AKT, GSK‐3β and mTOR. Mechanistically, PI3K pathway inhibition lead to enhanced apoptosis and decreased cellular proliferation linked to reduced Cyclin D1 and increased p27KIP1 levels. Simultaneous treatment of synovial sarcoma cell lines with LY294002 and cytotoxic drugs resulted in additive effects. In summary, PI3K signaling plays an essential role in growth control of synovial sarcomas and might be successfully targeted in multimodal therapeutic strategies.
Runx3 suppresses gastric cancer metastasis through inactivation of MMP9 by upregulation of TIMP‐1
Authors: Chen Yu , Wei Xufeng , Guo Changcun , Jin Haifeng , Han Zheyi , Han Ying , Qiao Taidong , Wu Kaichun , Fan Daiming 
Published: December 2010

AbstractRecent studies have suggested that loss of RUNX3 expression is involved with gastric tumor metastasis. However, the precise mechanism of RUNX3‐mediated suppression of tumor metastasis remains elusive. We aimed to clarify the effect of RUNX3 on tumor metastasis in gastric cancer cell lines and tumors. Immunohistochemistry revealed that RUNX3 was significantly decreased in metastatic gastric cancer. Gelatin zymography and Western blot showed that instead of regulating matrix metalloproteinase 9 (MMP9) expression, RUNX3 expression inhibited MMP9 enzyme activity, and this was consistent with the upregulation of tissue inhibitor of metalloproteinases 1 (TIMP1) by RUNX3. TIMP1 siRNA treatment impaired RUNX3‐mediated suppression of gastric cancer cell invasion. Reporter assays demonstrated regulation of TIMP‐1 by RUNX3. Two RUNX3 binding sites were identified in the TIMP‐1 promoter and direct interaction of RUNX3 with the TIMP‐1 promoter was confirmed in vitro and in vivo. These findings provide evidence for RUNX3‐mediated suppression of gastric cancer invasion and metastasis and define a novel molecular mechanism that for the metastasis‐inhibiting activity of RUNX3. These data may be applied in the development of RUNX3 for gastric cancer metastasis diagnostics and therapeutics.
Renal osteodystrophy in the first decade of the new millennium: Analysis of 630 bone biopsies in black and white patients
Authors: Malluche Hartmut H , Mawad Hanna W , Monier-Faugere Marie-Claude 
Published: December 2010

AbstractRenal osteodystrophy occurs early during loss of kidney function. There are 26 million American patients with chronic kidney disease (CKD), and almost all patients with CKD stage 5 have abnormal bone histology. Six hundred and thirty bone biopsies from adult CKD-5 patients on dialysis were evaluated by histomorphometry and analyzed using the turnover (T), mineralization (M), and volume (V) classification. There were racial differences; whites exhibited predominantly low turnover (62%), whereas blacks showed mostly normal or high turnover (68%). A mineralization defect was observed in only 3% of patients. In whites, cancellous bone volume was low, normal, or high in approximately the same number of patients, whereas in blacks, cancellous bone volume was high in two-thirds of the patients. More than 80% of blacks and whites with low cancellous bone volume had thin trabeculae owing to low bone formation. Cortical thickness was low in half the whites, whereas it was normal in three-quarters of blacks. Cortical porosity was high in 50% of whites, whereas three-quarters of blacks had high porosity. In summary, the TMV system gives relevant information. It should be expanded to include the architecture of cancellous and cortical bone. There are racial differences. Low bone volume and low bone turnover are more frequent than heretofore appreciated, whereas mineralization defects nowadays are observed rarely in adults. These findings call for an adjustment of the current therapeutic paradigm that takes into consideration race and risk of low bone volume and turnover. The latter have been shown to be associated with increased vascular calcifications. © 2011 American Society for Bone and Mineral Research.
Ethnic identity, sense of community, and psychological well‐being among northern plains American Indian youth
Authors: Kenyon DenYelle Baete , Carter Jessica S. 
Published: December 2010

AbstractLimited research has examined how ethnic identity and sense of community may be associated with psychological well‐being in American Indian adolescents. Via survey data, we examined the relationships among ethnic identity, sense of community, psychosomatic symptoms, positive affect, and feelings of depression with students from a tribal high school (N=95; n=37 males; n=58 females; aged 14.4–20.95 years; mean=17.3, SD=1.47 years). A majority of the sample self‐identified as American Indian/Native American (85.3%), with small percentages reporting additional ethnic backgrounds. Analyses revealed a significant difference in sense of community and positive affect by ethnic identity group. Post hoc analyses demonstrated adolescents in the “achieved” identity group were significantly higher on sense of community and positive affect than the other three groups. However, there were no significant differences on feelings of depression or psychosomatic symptoms by ethnic identity group. Implications for interventions are discussed. © 2010 Wiley Periodicals, Inc.
School engagement, risky peers, and student–teacher relationships as mediators of school violence in Taiwanese vocational versus academically oriented high schools
Authors: Chen Ji‐Kang , Astor Ron Avi 
Published: December 2010

AbstractEducational tracking based on academic ability accounts for different school dynamics between vocational versus academically‐oriented high schools in Taiwan. Many educational practitioners predict that the settings of vocational schools and academic schools mediate school violence in different ways. Alternatively, some researchers argue the actual mediating mechanism may not vary significantly between the different school types in different cultures. The purpose of this study was to examine how within‐school variables (school engagement, risky peers, and student–teacher interaction) mediate external‐school variables (personal traits, parental monitoring, and victimization) and school violence in Taiwanese vocational and academically‐oriented schools. Structural equation modeling analysis, based on a national representative sample (N=7,841), suggested school violence was mediated through school variables. Similar mediational findings were found between academic and vocational schools as well as between males and females. Findings suggest that school violence is mediated by within‐school variables in similar ways across different school types, genders, and cultures. © 2010 Wiley Periodicals, Inc.
The perception of neighborhood disorder in flemish Belgium: differences between ethnic majority and minority group members and bearing on fear of crime
Authors: Vancluysen Kris , Van Craen Maarten , Ackaert Johan 
Published: December 2010

AbstractThe present research examines whether the perception of neighborhood disorder differs between ethnic majority and minority group members and whether perceived disorder has the same impact on fear of crime among ethnic minorities as among the majority group. To answer the research questions, data are used from a survey among persons of Moroccan, Turkish, and Flemish descent (n=960), gathered in three Flemish Belgian cities (Antwerp, Genk, and Ghent). Multiple regression analyses show differences between majority and minority group members with regard to the perception of loitering youths, dog mess, and littering. Also, results provide support for the broken windows hypothesis in all ethnic groups, but the impact of perceived disorder on fear of crime is highest among the Flemish majority. Possible explanations are discussed. © 2010 Wiley Periodicals, Inc.
Validation of a novel LC‐MS/MS method for the quantitation of colistin A and B in human plasma
Authors: Dotsikas Yannis , Markopoulou Catherine K. , Koundourellis John E. , Loukas Yannis L. 
Published: December 2010

AbstractA liquid chromatography/tandem mass spectrometry (LC‐MS/MS) method, characterized by complete automation and high‐throughput, was developed for the determination of colistin A and B in human plasma. All sample preparation procedures were performed by using 2.2 mL 96‐deep‐well plates, whereas robotic liquid‐handling workstations were utilized for all liquid transfer steps, including solid‐phase extraction (SPE). The whole preparation procedure was very rapid, whereas the method had a very short chromatographic run time of just 2 min. Sample analysis was performed by reversed phase LC‐MS/MS, with positive electrospray ionization, using multiple reaction monitoring. The absence of available purified colistin A and B standards led to the development of a novel LC method with evaporative light‐scattering detector for the determination of their stoichiometries in the standard mixture, along with its purity. The proposed bioanalytical method was fully validated and it was proven to be selective, accurate, precise, reproducible and suitable for the determination of colistin A and B in human plasma. It was applied successfully to a pharmacokinetic study for the determination of both analytes in samples of patients.
Few‐optical‐cycle light pulses with passive carrier‐envelope phase stabilization
Authors: Cerullo G. , Baltuška A. , Mücke O.D. , Vozzi C. 
Published: December 2010

AbstractOne of the most advanced frontiers of ultrafast optics is the control of carrier‐envelope phase (CEP) ϕ of light pulses, which enables the generation of optical waveforms with reproducible electric field profile. Such control is important for pulses with few‐optical‐cycle duration, for which a CEP variation produces a strong change in the waveform, so that strongly nonlinear optical phenomena, such as multiphoton absorption, above‐threshold ionization and high‐harmonic generation become CEP‐dependent. In particular, CEP control is the prerequisite for the production of isolated attosecond pulses. Standard laser systems generate pulses that are CEP unstable; the CEP can be stabilized using either active or passive methods. Passive, all‐optical schemes rely on difference‐frequency generation (DFG) between two pulses sharing the same CEP: in this process the phases of the two pulses add up with opposite signs, leading to cancellation of the shot‐to‐shot CEP fluctuations. This paper presents an overview of passive CEP stabilization schemes, starting from the basic concepts and progressing to the details of the practical implementations of the idea. The passive approach allows the generation of CEP‐controlled few‐optical‐cycle pulses covering a very broad range of parameters in terms of carrier frequency (from visible to mid‐IR), energy (up to several mJs) and repetition rate (up to hundreds of kHz)
Organische Verbindungen in Pflanzen: das Matrixproblem
Authors: Mothes Falko , Reiche Nils , Fiedler Petra , Möder Monika , Borsdorf Helko 
Published: December 2010

AbstractPflanzenkläranlagen sollen kontaminierte Grundwässer reinigen. Damit das effizient geschieht, muss mehr über Abbau, Verteilungs‐ und Transportprozesse in dem System bekannt sein. Dazu ist beispielsweise Benzol in Schilfpflanzen zu bestimmen. Ein Knackpunkt ist die Probenvorbereitung.
Aus dem Blut ins LC‐MS/MS
Authors: Remane Daniela , Meyer Markus R. , Maurer Hans H. 
Published: December 2010

AbstractSchnell, einfach, kostengünstig und effektiv — wie lassen sich 136 verschiedene Arzneistoffe aus Blutplasma zur anschließenden Messung im LC‐MS/MS extrahieren?
Chemikerinnen? Fehlanzeige!
Authors: Osterath Brigitte 
Published: December 2010

AbstractFernsehserien entführen in Welten, zu denen junge Mädchen meist keinen Kontakt haben. Gäbe es mehr Chemikerinnen in Deutschland, wenn in den Seifenopern und Krimis mehr Wissenschaftlerinnen mitspielten?
Spinnenseide aus Sicht der Polymerforschung
Authors: Groß Michael 
Published: December 2010

AbstractRheologische Untersuchungen zeigen, dass sich das Rohmaterial, aus dem die Spinne ihre Fäden spinnt, wie geschmolzenes Polymer verhält. Ansätze aus der Polymerforschung helfen also, die Eigenschaften des Materials zu verstehen und nachzuahmen.
Scheduling with centralized and decentralized batching policies in concurrent open shops
Authors: Lin B. M. T. , Cheng T. C. E. 
Published: December 2010

AbstractThis article considers batch scheduling with centralized and decentralized decisions. The context of our study is concurrent open shop scheduling where the jobs are to be processed on a set of independent dedicated machines, which process designated operations of the jobs in batches. The batching policy across the machines can be centralized or decentralized. We study such scheduling problems with the objectives of minimizing the maximum lateness, weighted number of tardy jobs, and total weighted completion time, when the job sequence is determined in advance. We present polynomial time dynamic programming algorithms for some cases of these problems and pseudo‐polynomial time algorithms for some problems that are NP‐hard in the ordinary sense. © 2010 Wiley Periodicals, Inc. Naval Research Logistics 58: 17–27, 2011
PMEPA1 promotes androgen receptor‐negative prostate cell proliferation through suppressing the Smad3/4–c‐Myc–p21$^{{\rm Cip1}}$ signaling pathway
Authors: Liu Rong , Zhou Zhongmei , Huang Jian , Chen Ceshi 
Published: December 2010

AbstractThe PMEPA1 gene has been shown to suppress the androgen receptor (AR) and TGFβ signaling pathways and is abnormally expressed in prostate tumours. However, the role and mechanism action of PMEPA1 in AR‐negative prostate cancer are unclear. Here, we demonstrate that inhibition of PMEPA1 suppresses AR‐negative RWPE1 and PC‐3 prostate cell proliferation through up‐regulating the p21 transcription. Additionally, PMEPA1 overexpression suppresses the p21 expression and promotes cell proliferation. PMEPA1 is induced by TGFβ as a negative feedback loop to suppress Smad3 phosphorylation and nuclear translocation; up‐regulates c‐Myc; down‐regulates p21; and promotes PC‐3 cell proliferation. The PMEPA1 functions depend on its Smad2/3 binding motif. Consistently, depletion of Smad3/4, but not Smad2, blocks PMEPA1's functions of regulating c‐Myc and p21. Importantly, stable depletion of PMEPA1 in PC‐3 inhibits xenograft growth. Finally, we found that PMEPA1 is overexpressed in a subset of prostate cancer cell lines and tumours. These findings suggest that PMEPA1 may promote AR‐negative prostate cancer cell proliferation through p21. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.