bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Role for Focal Adhesion Kinase Signaling in Tumor Necrosis Factor-α–Dependent Matrix Metalloproteinase-9 Production in a Cholangiocarcinoma Cell Line, CCKS1
Authors: Mon Naing Naing , Hasegawa Hitoki , Thant Aye Aye , Huang Pengyu , Tanimura Yoko , Senga Takeshi , Hamaguchi Michinari 
Published: July 2006

Abstract
We have previously reported that tumor necrosis factor-α (TNF-α) stimulation of CCKS1, a cell line established from cholangiocarcinoma with i.p. dissemination, dramatically increased matrix metalloproteinase-9 (MMP-9) production and tumor invasion. We investigated the role of focal adhesion kinase (FAK) in TNF-α–dependent production of MMP-9 in CCKS1 and FAK-null mouse fibroblast cells. TNF-α stimulation of CCKS1 or wild-type fibroblasts substantially activated FAK phosphorylation and increased MMP-9 production. In contrast, FAK-null fibroblasts could not respond well to TNF-α stimulation. Conditional expression of wild-type FAK in FAK-null cells restored the TNF-α–dependent production of MMP-9. TNF-α treatment activated the kinase activity of FAK and its phosphorylation especially at Y397 and Y925. Phosphorylated FAK accumulated at focal adhesions and formed a complex with growth factor receptor binding protein 2 and SOS. In contrast, Y397F FAK and Y925F FAK, whose Y397 and Y925 were replaced with phenylalanine, respectively, as well as KD FAK, whose kinase was inactivated, could not restore the MMP-9 production. In addition, small interfering RNA against FAK drastically suppressed the TNF-α–dependent production of MMP-9 and inhibited the TNF-α–dependent invasion of CCKS1. Taken together, our results suggest the pivotal role of FAK in TNF-α–dependent production of MMP-9 and subsequent activation of tumor invasion. (Cancer Res 2006; 66(13): 6778-84)
Antibody Targeting of Long-Circulating Lipidic Nanoparticles Does Not Increase Tumor Localization but Does Increase Internalization in Animal Models
Authors: Kirpotin Dmitri B. , Drummond Daryl C. , Shao Yi , Shalaby M. Refaat , Hong Keelung , Nielsen Ulrik B. , Marks James D. , Benz Christopher C. , Park John W. 
Published: July 2006

AbstractWe describe evidence for a novel mechanism of monoclonal antibody (MAb)–directed nanoparticle (immunoliposome) targeting to solid tumors in vivo. Long-circulating immunoliposomes targeted to HER2 (ErbB2, Neu) were prepared by the conjugation of anti-HER2 MAb fragments (Fab′ or single chain Fv) to liposome-grafted polyethylene glycol chains. MAb fragment conjugation did not affect the biodistribution or long-circulating properties of i.v.-administered liposomes. However, antibody-directed targeting also did not increase the tumor localization of immunoliposomes, as both targeted and nontargeted liposomes achieved similarly high levels (7-8% injected dose/g tumor tissue) of tumor tissue accumulation in HER2-overexpressing breast cancer xenografts (BT-474). Studies using colloidal gold-labeled liposomes showed the accumulation of anti-HER2 immunoliposomes within cancer cells, whereas matched nontargeted liposomes were located predominantly in extracellular stroma or within macrophages. A similar pattern of stromal accumulation without cancer cell internalization was observed for anti-HER2 immunoliposomes in non–HER2-overexpressing breast cancer xenografts (MCF-7). Flow cytometry of disaggregated tumors posttreatment with either liposomes or immunoliposomes showed up to 6-fold greater intracellular uptake in cancer cells due to targeting. Thus, in contrast to nontargeted liposomes, anti-HER2 immunoliposomes achieved intracellular drug delivery via MAb-mediated endocytosis, and this, rather than increased uptake in tumor tissue, was correlated with superior antitumor activity. Immunoliposomes capable of selective internalization in cancer cells in vivo may provide new opportunities for drug delivery. (Cancer Res 2006; 66(13): 6732-40)
HDJ-2 as a Target for Radiosensitization of Glioblastoma Multiforme Cells by the Farnesyltransferase Inhibitor R115777 and the Role of the p53/p21 Pathway
Authors: Wang Chun-Chieh , Liao Yu-Pei , Mischel Paul S. , Iwamoto Keisuke S. , Cacalano Nicholas A. , McBride William H. 
Published: July 2006

Abstract
Resistance of glioblastoma multiforme to radiotherapy poses a major clinical challenge. Farnesyltransferase inhibitors (FTI), such as R115777, have potential to increase radiotherapeutic benefit in this disease, although their mechanism of action is unclear. In our study with eight glioblastoma multiforme cell lines, the most sensitive ones underwent cell cycle arrest in response to FTI treatment. Radiosensitization by FTIs, however, seemed to involve other pathways. If R115777 treatment was initiated &lt;6 hours before irradiation, all eight glioblastoma multiforme lines were radiosensitized. However, if the time between drug and radiation was extended to 24 hours, cells harboring wild type but not mutated p53 were able to counteract drug-induced radiosensitization. The involvement of the p53/p21 pathway in the development of resistance was confirmed by showing that U87 cells transfected with human papillomavirus E6 to block p53 or interfering RNA to inhibit p21 stayed radiosensitive for 24 hours after drug treatment. The time dependency of R115777-induced radiosensitization suggested that the initial FTI target for early radiosensitization was short-lived, and that a p21-directed pathway restored resistance. Consideration of prenylated molecules that could potentially be involved led us to consider HDJ-2, a co-chaperone of heat shock protein 70. This hypothesis was strengthened by finding that cellular radiosensitivity was increased by genetic inhibition of HDJ-2, whereas overexpression conferred radioresistance. Importantly, irradiation of cells caused HDJ-2 to migrate from the cytoplasm to the nucleus, and this migration was inhibited by prior FTI treatment. These results have clinical relevance in that they help explain the variability in responses to FTIs that occurs following radiotherapy and elucidate some of the reasons for the complexity underlying FTI-induced radiosensitization. (Cancer Res 2006; 66(13): 6756-62)
Conditional Activation of RET/PTC3 and BRAFV600E in Thyroid Cells Is Associated with Gene Expression Profiles that Predict a Preferential Role of BRAF in Extracellular Matrix Remodeling
Authors: Mesa Cleo , Mirza Mana , Mitsutake Norisato , Sartor Maureen , Medvedovic Mario , Tomlinson Craig , Knauf Jeffrey A , Weber Georg F. , Fagin James A. 
Published: July 2006

Abstract
Papillary thyroid cancers (PTC) are associated with nonoverlapping mutations of genes coding for mitogen-activated protein kinase signaling effectors (i.e., the TK receptors RET or NTRK and the signaling proteins RAS and BRAF). We examined the pattern of gene expression after activation of these oncoproteins in thyroid PCCL3 cells, with the goal of identifying pathways or gene subsets that may account for the phenotypic differences observed in human cancers. We hybridized cDNA from cells treated with or without doxycycline to induce expression of BRAFV600E, RET/PTC3, or RET/PTC3 with small interfering RNA–mediated knockdown of BRAF, respectively, to slides arrayed with a rat 70-mer oligonucleotide library consisting of 27,342 oligos. Among the RET/PTC3-induced genes, 2,552 did not require BRAF as they were similarly regulated by RET/PTC3 with or without BRAF knockdown and not by expression of BRAFV600E. Immune response and IFN-related genes were highly represented in this group. About 24% of RET/PTC3-regulated genes were BRAF dependent, as they were similarly modified by RET/PTC3 and BRAFV600E but not in cells expressing RET/PTC3 with knockdown of BRAF. A gene cluster coding for components of the mitochondrial electron transport chain pathway was down-regulated in this group, potentially altering regulation of cell viability. Metalloproteinases were also preferentially induced by BRAF, particularly matrix metalloproteinase 3 (MMP3), MMP9, and MMP13. Accordingly, conditional expression of BRAF was associated with markedly increased invasion into Matrigel compared with cells expressing RET/PTC3. The preferential induction of MMPs by BRAF could explain in part the more invasive behavior of thyroid cancers with BRAF mutations. (Cancer Res 2006; 66(13): 6521-9)
A Role for the WWOX Gene in Prostate Cancer
Authors: Qin Haiyan R. , Iliopoulos Dimitrios , Semba Shuho , Fabbri Muller , Druck Teresa , Volinia Stefano , Croce Carlo M. , Morrison Carl D. , Klein Russell D. , Huebner Kay 
Published: July 2006

Abstract
Expression of the WWOX gene, encompassing the common chromosome fragile site FRA16D, is altered in a large fraction of cancers of various types, including prostate cancer. We have examined expression and biological functions of WWOX in prostate cancer. WWOX mRNA and protein expression were significantly reduced in prostate cancer-derived cells (LNCaP, DU145, and PC-3) compared with noncancer prostate cells (PWR-1E), and WWOX expression was reduced in 84% of prostate cancers, as assessed by immunohistochemical staining. Down-modulation of WWOX expression in the prostate cancer-derived cells is due to DNA hypermethylation in the WWOX regulatory region. Treatment with 5-aza-2′-deoxycytidine (AZA), a DNA methyltransferase inhibitor, and trichostatin A, a histone deacetylase inhibitor, led to increased WWOX mRNA and protein expression in prostate cancer-derived cells, most strikingly in DU145 cells. Transfection-mediated WWOX overexpression in DU145 cells suppressed colony growth (P = 0.0012), and WWOX overexpression by infection with Ad-WWOX virus induced apoptosis through a caspase-dependent mechanism and suppressed cell growth. Lastly, ectopic expression of WWOX by Ad-WWOX infection suppressed tumorigenicity of xenografts in nude mice, and intratumoral AZA treatment halted tumor growth. The data are consistent with a role for WWOX as a prostate cancer tumor suppressor and suggest that WWOX signal pathways should be further investigated in normal and cancerous prostate cells and tissues. (Cancer Res 2006; 66(13): 6477-81)
First Three Years of the Microwave Radiometer aboard Envisat: In-Flight Calibration, Processing, and Validation of the Geophysical Products
Authors: Obligis E. , Eymard L. , Tran N. , Labroue S. , Femenias P. 
Published: July 2006

AbstractThe Envisat microwave radiometer is designed to correct the satellite altimeter data for the excess path delay resulting from tropospheric humidity. Neural networks have been used to formulate the inversion algorithm to retrieve this quantity from the measured brightness temperatures. The learning database has been built with European Centre for Medium-Range Weather Forecasts (ECMWF) analyses and simulated brightness temperatures by a radiative transfer model. The in-flight calibration has been performed in a consistent way by adjusting measurements on simulated brightness temperatures. Finally, coincident radiosonde measurements are used to validate the Envisat wet-tropospheric correction, and this comparison shows the good performances of the method.
Comparison of Reynolds Stress Estimates Derived from Standard and Fast-Ping ADCPs
Authors: Nidzieko Nicholas J. , Fong Derek A. , Hench James L. 
Published: July 2006

Abstract
A field experiment was conducted to directly compare the effects of different sampling modes on Reynolds stress estimates calculated from acoustic Doppler current profilers (ADCPs). Two 1.2-MHz ADCPs were deployed concurrently over a fortnightly cycle: one collected single-ping measurements using mode 1 and a second ADCP employed the fast-ping rate mode 12 with subping-averaged data recorded at the same sample rate as the first ADCP. While mode 12 clearly has a lower noise floor for the estimate of mean velocities, it has been an open question whether the averaging of subpings leads to a biased estimate of turbulence quantities, due to the temporal averaging inherent in this approach. Using the variance method, Reynolds stresses were estimated from the two ADCP datasets and compared with stresses computed directly from the velocity records obtained with a pair of fast sampling acoustic Doppler velocimeters (ADVs) collocated with the ADCPs. Mode-12 stresses were more accurate than mode 1 in comparison to ADV-derived stresses, and mode 12 exhibited much lower measurement uncertainty than mode 1. Mode 1 appears to overestimate stresses by 20% in this study. The lower noise floor associated with mode 12 suggests that the variance method may be used with mode 12 to resolve smaller stresses than would be possible with mode 1.
Routes to improving the reliability of low level DNA analysis using real-time PCR
Authors: Ellison Stephen LR , English Claire A , Burns Malcolm J , Keer Jacquie T 
Published: July 2006

Abstract

Background
Accurate quantification of DNA using quantitative real-time PCR at low levels is increasingly important for clinical, environmental and forensic applications. At low concentration levels (here referring to under 100 target copies) DNA quantification is sensitive to losses during preparation, and suffers from appreciable valid non-detection rates for sampling reasons. This paper reports studies on a real-time quantitative PCR assay targeting a region of the human SRY gene over a concentration range of 0.5 to 1000 target copies. The effects of different sample preparation and calibration methods on quantitative accuracy were investigated.

Results
At very low target concentrations of 0.5–10 genome equivalents (g.e.) eliminating any replicates within each DNA standard concentration with no measurable signal (non-detects) compromised calibration. Improved calibration could be achieved by eliminating all calibration replicates for any calibration standard concentration with non-detects ('elimination by sample'). Test samples also showed positive bias if non-detects were removed prior to averaging; less biased results were obtained by converting to concentration, including non-detects as zero concentration, and averaging all values.
Tube plastic proved to have a strongly significant effect on DNA quantitation at low levels (p = 1.8 × 10-4). At low concentrations (under 10 g.e.), results for assays prepared in standard plastic were reduced by about 50% compared to the low-retention plastic. Preparation solution (carrier DNA or stabiliser) was not found to have a significant effect in this study.
Detection probabilities were calculated using logistic regression. Logistic regression over large concentration ranges proved sensitive to non-detected replicate reactions due to amplification failure at high concentrations; the effect could be reduced by regression against log (concentration) or, better, by eliminating invalid responses.

Conclusion
Use of low-retention plastic tubes is advised for quantification of DNA solutions at levels below 100 g.e. For low-level calibration using linear least squares, it is better to eliminate the entire replicate group for any standard that shows non-detects reasonably attributable to sampling effects than to either eliminate non-detects or to assign arbitrary high Ct values. In calculating concentrations for low-level test samples with non-detects, concentrations should be calculated for each replicate, zero concentration assigned to non-detects, and all resulting concentration values averaged. Logistic regression is a useful method of estimating detection probability at low DNA concentrations.
Food neophobia and mealtime food consumption in 4–5 year old children
Authors: Cooke Lucy , Carnell Susan , Wardle Jane 
Published: July 2006

Abstract

Background
Previous research has documented a negative association between maternal report of child food neophobia and reported frequency of consumption of fruit, vegetables, and meat. This study aimed to establish whether neophobia is associated with lower intake of these food types in naturalistic mealtime situations.

Methods
One hundred and nine parents of 4–5 year olds completed questionnaires which included a six-item version of the Child Food Neophobia Scale (CFNS). The children took part in a series of 3 test lunch meals at weekly intervals at school at which they were presented with: chicken, cheese, bread, cheese crackers, chocolate biscuits, grapes and tomatoes or carrot sticks. Food items served to each child were weighed before and after the meal to assess total intake of items in four categories: Fruit and vegetables, Protein foods, Starchy foods and Snack foods. Pearson Product Moment Correlations and independent t tests were performed to examine associations between scores on the CFNS and consumption during lunches.

Results
Neophobia was associated with lower consumption of fruit and vegetables, protein foods and total calories, but there was no association with intake of starch or snack foods.

Conclusion
These results support previous research that has suggested that neophobia impacts differentially on consumption of different food types. Specifically it appears that children who score highly on the CFNS eat less fruit, vegetables and protein foods than their less neophobic peers. Attempts to increase intake of fruit, vegetables and protein might usefully incorporate strategies known to reduce the neophobic response.
Adipose tissue of human omentum is a major source of dendritic cells, which lose MHC Class II and stimulatory function in Crohn's disease
Authors: Bedford Penelope A , Todorovic Vesna , Westcott Edward D A , Windsor Alistair C J , English Nicholas R , Al-Hassi Hafid Omar , Raju Kankipati S , Mills Sarah , Knight Stella C 
Published: July 2006

Abstract
Adipose tissue is reported to contain monocyte-like pre-adipocytes, which may mature into macrophages, contributing to local inflammation. Dendritic cells (DC) can be derived from monocytes and initiate and regulate primary immune responses. We hypothesized, therefore, that adipose tissue may provide DC involved in local immune activity. To test this, we studied cells from human omental adipose tissue samples from 17 patients with benign gynecological disease. The hypothesis that adipose tissue DC are involved in inflammatory disease was tested by comparing these cells with those from 18 patients with Crohn's disease, where hypertrophy of adipose tissue suggests involvement in disease. A high proportion of the 1.33 ± 0.12 × 105 CD45-positive cells/mg, obtained from control omenta, expressed CD11c, CD1a, and CD83; costimulatory molecules CD40, CD80, and CD86; and major histocompatibility complex (MHC) Class II but little CD14, CD16, or CD33. Omental cells showing morphological characteristics of DC were also observed. Metrizamide gradient-enriched DC from these populations were potent stimulators of primary proliferation of allogeneic T cells in mixed leukocyte reactions. Increased numbers of CD45+ cells from omentum of Crohn's patients (4.50±1.08×105 CD45+ cells/mg) contained higher percentages of CD11c+ and CD40+ cells (80.8±3.8% vs. 63.4±6, P=0.032; 77.9±4% vs. 58.8±6.5, P=0.029, respectively), but MHC Class II and stimulatory capacity were almost completely lost (P=&lt;0.001), suggesting innate activation but lost capacity to stimulate adaptive immune responses. Granulocytes were also present amongst the omental cells from Crohn's patients. Results indicated that omentum may provide DC, which could “police” local infections and contribute to and/or reflect local inflammatory activity.
The Suppressor of Cytokine Signaling 3 Inhibits Leptin Activation of AMP-Kinase in Cultured Skeletal Muscle of Obese Humans
Authors: Steinberg Gregory R. , McAinch Andrew J. , Chen Michael B. , O’Brien Paul E. , Dixon John B. , Cameron-Smith David , Kemp Bruce E. 
Published: July 2006

Abstract
Context: Leptin is thought to regulate whole-body adiposity and insulin sensitivity, at least in part, by stimulating fatty acid metabolism via activation of AMP-kinase (AMPK) in skeletal muscle. Human obesity is associated with leptin resistance, and recent studies have demonstrated that hypothalamic expression of the suppressors of cytokine signaling 3 (SOCS3) regulates leptin sensitivity in rodents.
Objective: The objective of the study was to investigate the effects of leptin on fatty acid oxidation and AMPK signaling in primary myotubes derived from lean and obese skeletal muscle and evaluate the contribution of SOCS3 to leptin resistance and AMPK signaling in obese humans.
Results: We demonstrate that leptin stimulates AMPK activity and increases AMPK Thr172 and acetyl-CoA carboxylase-β Ser222 phosphorylation and fatty acid oxidation in lean myotubes but that in obese subjects leptin-dependent AMPK signaling and fatty acid oxidation are suppressed. Reduced activation of AMPK was associated with elevated expression of IL-6 (∼3.5-fold) and SOCS3 mRNA (∼2.5-fold) in myotubes of obese subjects. Overexpression of SOCS3 via adenovirus-mediated infection in lean myotubes to a similar degree as observed in obese myotubes prevented leptin but not AICAR (5-amino-imidazole-4-carboxamide-1-β-d-ribofuranoside) activation of AMPK signaling.
Conclusions: These data demonstrate that SOCS3 inhibits leptin activation of AMPK. These data suggest that this impairment of leptin signaling in skeletal muscle may contribute to the aberrant regulation of fatty acid metabolism observed in obesity and that pharmacological activation of AMPK may be an effective therapy to bypass SOCS3-mediated skeletal muscle leptin resistance for the treatment of obesity-related disorders.
Mechanism of Sulfur Inversion in Sulfide Complexes of Gold(I) and Gold(III)
Authors: Toyota Shinji , Oki Michinori 
Published: July 2006

Abstract
Kinetic parameters for the sulfur inversion in various gold chloride complexes of alkyl benzyl sulfides were measured by the dynamic NMR method in order to obtain conclusive evidence for the inversion mechanism. A feature of kinetic data is that entropies of activation are nearly zero both in the gold(III) and gold(I) complexes, this suggesting that the sulfur inversion takes place via pyramidal inversion mechanism without breakage of the Au–S coordination bonds but not the dissociative mechanism. The negligible solvent effect on the inversion rates in the gold(III) and gold(I) complexes supports this mechanism as well. The barrier to sulfur inversion is higher by 2.9 kcal mol−1 in the gold(III) complexes than in the corresponding gold(I) complexes. The formal gold(II) complex exists as 1 : 1 mixture of gold(I) and gold(III) complexes in solution, each of them showing the dynamic behavior independently. The effect of oxidation state of the central gold atom on the sulfur inversion is discussed on the basis of MO calculation.
Reactions of Sulfoxides with Magnesium Amides. Transformation of Sulfoxides into Sulfides, Dithioacetals, and Vinyl Sulfides
Authors: Kobayashi Kazuhiro , Kawakita Masataka , Yokota Kouichi , Mannami Tohru , Yamamoto Koji , Morikawa Osamu , Konishi Hisatoshi 
Published: July 2006

Abstract
The reactions of sulfoxides with magnesium amides generated in situ from the reaction of ethylmagnesium bromide and secondary amines, such as diisopropylamine (DIPA) or 2,2,6,6-tetramethylpiperidine (TMP) in diethyl ether, were examined. Diaryl sulfoxides were heated with the diisopropylaminomagnesium reagent in diethyl ether to give the corresponding diaryl sulfides in 42—52% yields. Sulfoxides bearing hydrogens at the α-positon only (RSOCH2R1) reacted with the tetramethylpiperidinomagnesium reagent at room temperature to produce the corresponding dithioacetals (RSCHR1SR) in 47—86% yields. The treatment of sulfoxides bearing hydrogens both at the α- and β-positions (RSOCHR1CHR2R3) with the magnesium amides at room temperature afforded the corresponding vinyl sulfides (RSCR1=CR2R3) in 52—72% yields accompanying 2.3—27% yields of the corresponding dithioacetals. The pathways leading to the products involving the formation of the sulfur-stabilized carbonium ion intermediates are discussed.