bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medial temporal lobe activity at recognition increases with the duration of mnemonic delay during an object working memory task
Authors: Picchioni Marco , Matthiasson Pall , Broome Matthew , Giampietro Vincent , Brammer Mick , Mathes Birgit , Fletcher Paul , Williams Steven , McGuire Philip 
Published: March 2007

AbstractObject working memory (WM) engages a disseminated neural network, although the extent to which the length of time that data is held in WM influences regional activity within this network is unclear. We used functional magnetic resonance imaging to study a delayed matching to sample task in 14 healthy subjects, manipulating the duration of mnemonic delay. Across all lengths of delay, successful recognition was associated with the bilateral engagement of the inferior and middle frontal gyri and insula, the medial and inferior temporal, dorsal anterior cingulate and the posterior parietal cortices. As the length of time that data was held in WM increased, activation at recognition increased in the medial temporal, medial occipito‐temporal, anterior cingulate and posterior parietal cortices. These results confirm the components of an object WM network required for successful recognition, and suggest that parts of this network, including the medial temporal cortex, are sensitive to the duration of mnemonic delay. Hum Brain Mapp 2007. © 2006 Wiley‐Liss, Inc.
Review: new biological insights in early clinical studies
Authors: Maur Michela , Sessa Cristiana 
Published: March 2007

AbstractFirst in human phase I trials are an unaviodable gateway to the development of new anticancer therapies. The discovery of target therapies have significantly changed the process of clinical drug development.This short review will focus on the main features including knowledge of biological aspects, methodology and adequacy of design and of performance of early clinical studies. Copyright © 2007 John Wiley & Sons, Ltd.
Doxorubicin cardiomyopathy via TLR‐2 stimulation: potential for prevention using current anti‐retroviral inhibitors such as ritonavir and nelfinavir
Authors: Kast R. E. , Foley K. F. , Focosi D. 
Published: March 2007

AbstractDoxorubicin remains a useful anti‐cancer drug but as lifetime dose approaches 500 mg/m2 and particularly when this dose is exceeded, iatrogenic life‐threatening cardiomyopathy becomes progressively more likely. This note reviews evidence indicating that doxorubicin induced cardiomyopathy is partly mediated by stimulation of Toll‐like receptors (TLR) 2 and 4 which are expressed on cardiomyocytes. Indinavir, nelfinavir, ritonavir, and saquinavir are currently marketed protease inhibitors used to suppress human immunodeficiency virus. They have recently been shown to inhibit signalling at TLR 2 and 4 as well as intracellular events downstream from these receptors. It is possible that these FDA‐approved anti‐retroviral protease inhibitors could be used off‐label to diminish likelihood of doxorubicin cardiotoxicity permitting higher doxorubicin doses. We suggest that currently marketed anti‐viral protease inhibitors be investigated in animal models of doxorubicin cardiomyopathy and if such studies do indeed show protection, human studies be initiated. Copyright © 2007 John Wiley & Sons, Ltd.
Involvement of PPARγ and E‐cadherin/β‐catenin pathway in the antiproliferative effect of conjugated linoleic acid in MCF‐7 cells
Authors: Bocca Claudia , Bozzo Francesca , Francica Simona , Colombatto Sebastiano , Miglietta Antonella 
Published: March 2007

AbstractConjugated linoleic acid (CLA) is a naturally occurring fatty acid, which has been shown to exert beneficial effects against breast carcinogenesis. It has been reported that CLA could modulate cellular proliferation and differentiation through the activation of peroxisome proliferator‐activated receptors (PPARs). Among different PPAR isotypes, PPARγ is involved in growth inhibition of transformed cells. Ligands of PPARγ are considered as potential anticancer drugs, so CLA was tested for its ability to induce PPARγ expression in MCF‐7 breast cancer cells. The effects of CLA and of a specific synthetic PPARγ antagonist were evaluated on cell growth as well as on parameters responsible for cell growth regulation. We demonstrated here that CLA stimulated the expression of PPARγ to levels up to control and caused PPARγ translocation into the nucleus. Furthermore, the overexpression of PPARγ positively correlates with the inhibition of cell proliferation and with the modulation of ERK signaling induced by CLA; in all cases the administration of the antagonist reverted CLA effects. The PPAR‐signaling pathway is connected with the β‐catenin/E‐cadherin pathway, thus we evaluated CLA effects on the expression and cellular distribution of these proteins, which are involved in cell adhesion and responsible for invasive behavior. The treatment with CLA determined the up‐regulation and the redistribution of β‐catenin and E‐cadherin and the antagonist reverted only the effect on β‐catenin. These studies indicate that CLA regulates PPARγ expression by selectively acting as an agonist and may influence cell–cell adhesion and invasiveness of MCF‐7 cells. © 2007 Wiley‐Liss, Inc.
Expression of NF‐κB parallels COX‐2 expression in oral precancer and cancer: Association with smokeless tobacco
Authors: Sawhney Meenakshi , Rohatgi Nidhi , Kaur Jatinder , Shishodia Shishir , Sethi Gautam , Gupta Siddhartha D. , Deo Suryanaryana V. S. , Shukla Nootan K. , Aggarwal Bharat B. , Ralhan Ranju 
Published: March 2007

AbstractNuclear Factor‐κB (NF‐κB) activation and COX‐2 overexpression have been reported in head and neck cancer, but the relationship between these proteins remains to be investigated. To determine the relationship between NF‐κB and COX‐2 in Smokeless Tobacco (ST) associated oral tumorigenesis, we performed immunohistochemistry in serial sections from 107 OSCCs, 78 oral precancerous lesions (OPLs) (58 hyperplasias, 20 dysplasias) and 15 histologically normal oral tissues and correlated with clinicopathological data. Significant increase in NF‐κB and COX‐2 immunopositivity was observed from normal oral mucosa to OPLs to OSCCs (p = 0.009 and p = 0.002 respectively). Upregulation of NF‐κB and COX‐2 was observed as early as in hyperplasia [p = 0.006; OR = 6.1 and p = 0.003; OR = 7.6, respectively]. Expression of both proteins was found to be significantly associated in OPLs (p = 0.000; OR = 12.6) and OSCCs (p = 0.001; OR = 4.0). Intriguingly, khaini consumption correlated with NF‐κB immunopositivity in OPLs (p = 0.05, OR = 3.8) and OSCCs (p = 0.01, OR = 3.4) and with COX‐2 expression in OPLs (p = 0.03; OR = 4.3). In vitro experimental system of ST associated oral carcinogenesis was used to demonstrate ST (khaini) and NNK mediated activation of NF‐κB and COX‐2, supporting the clinical data. In conclusion, this study demonstrates correlation between over expression of NF‐κB and COX‐2 in early precancerous stages of development of oral cancer and sustained elevation down the tumorigenic pathway, underscoring their potential as targets for early intervention. In vitro studies demonstrated that NNK may be one of the carcinogenic components of ST (khaini) inducing activation of NF‐κB and COX‐2 in oral precancer and cancer cells, suggesting plausible role in ST‐induced oral carcinogenesis. © 2007 Wiley‐Liss, Inc.
Decreased intraperitoneal disease recurrence in epithelial ovarian cancer patients receiving intraperitoneal consolidation treatment with yttrium‐90‐labeled murine HMFG1 without improvement in overall survival
Authors: Oei Angèle L. , Verheijen René H. , Seiden Michael V. , Benigno Benedict B. , Lopes Alberto , Soper John T. , Epenetos Agamemnon A. , Massuger Leon F. 
Published: March 2007

AbstractThis study analyzes the site of disease recurrence in ovarian cancer patients to assess the influence of a single intraperitoneal (IP) administration of yttrium‐90‐labeled murine monoclonal antibody HMFG1 (90Y‐muHMFG1) on the pattern of disease recurrence. In a large phase III trial ovarian cancer patients in complete clinical remission with FIGO stage Ic‐IV were randomized between standard treatment plus a single IP 90Y‐labeled muHMFG1 versus standard treatment alone after negative second‐look laparoscopy. Case report forms of all patients with disease recurrence were reviewed to determine site and date of recurrent disease. In total 447 patients were included in the study with a median follow‐up of 3.5 years. Relapse was seen in 104/224 in the active and 98/223 in the control arm. Significantly fewer IP (p < 0.05) and more extraperitoneal (p < 0.05) relapses occurred in the active treatment arm. Time to IP recurrence was significantly longer (p = 0.0019) and time to extraperitoneal recurrence was significantly shorter for the active treatment arm (p < 0.001). The impact of IP radioimmunotherapy on IP relapse‐free survival could only be seen in the subgroup of patients with residual disease after primary surgery (HR, 0.31; 95% CI, 0.18 to 0.53; p = 0.002). Although, there is no survival benefit for IP radioimmunotherapy as consolidation treatment for epithelial ovarian cancer, we found an improved control of IP disease, that was offset by increased extraperitoneal recurrences. © 2007 Wiley‐Liss, Inc.
Meat and meat‐mutagen intake, doneness preference and the risk of colorectal polyps: The Tennessee colorectal polyp study
Authors: Shin Aesun , Shrubsole Martha J. , Ness Reid M. , Wu Huiyun , Sinha Rashmi , Smalley Walter E. , Shyr Yu , Zheng Wei 
Published: March 2007

AbstractAlthough meat intake has been fairly consistently linked to the risk of colorectal cancer, only a few studies have evaluated meat intake by doneness level and the heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) produced by high temperature cooking of meat in relation to colorectal adenomatous and hyperplastic polyps. We evaluated these associations in a large colonoscopy‐based case‐control study. Included in this study were participants with adenomatous polyp only (n = 573), hyperplastic polyp only (n = 256), or both adenomatous and hyperplastic polyps (n = 199), and 1,544 polyp‐free controls. In addition to information related to demographic and other lifestyle factors, meat intake by cooking method and doneness preference were obtained through telephone interviews. Polytomous logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals for the association between exposures and colorectal polyp risks. Presence of hyperplastic polyp was found to be positively associated with high consumption of total meat (ptrend = 0.076) or red meat (ptrend = 0.060), with an approximate 50–60% elevated risk observed in the highest vs. the lowest intake group. High intake of 2‐amino‐I‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) and 2‐amino‐3,4,8‐trimethylimidazo [4,5]quinoxaline (DiMeIQx) were associated with increased risk for hyperplastic polyp (ptrend = 0.036 and 0.038, respectively). With a possible exception of the intake of total well‐done meats (ptrend = 0.055) or well‐done red meats (ptrend = 0.074) with the risk of large adenomas, no other positive association was found specifically for the risk of adenomas with any of the exposure variables aforementioned. This study provides additional support for a positive association of high intake of red meat with colorectal adenomas, and suggests that high intake of meats and meat carcinogens may also be associated with hyperplastic polyps. © 2007 Wiley‐Liss, Inc.
Aberrant regulation of argininosuccinate synthetase by TNF‐α in human epithelial ovarian cancer
Authors: Szlosarek Peter W. , Grimshaw Matthew J. , Wilbanks George D. , Hagemann Thorsten , Wilson Julia L. , Burke Frances , Stamp Gordon , Balkwill Frances R. 
Published: March 2007

AbstractThe pro‐inflammatory cytokine, tumour necrosis factor‐α, TNF‐α, is dysregulated in malignant compared with normal ovarian surface epithelium (OSE). Several epidemiological studies have associated inflammation with ovarian tumorigenesis, with TNF‐α playing a key role in modulating invasion, angiogenesis and metastasis. Here, we show that TNF‐α also induces expression of arate‐limiting enzyme in arginine synthesis, argininosuccinate synthetase (AS), thereby linking inflammation with several arginine‐dependent metabolic pathways, implicated in accelerated carcinogenesis and tumour progression. Having identified AS mRNA induction in TNF‐α‐treated IGROV‐1 ovarian cancer cells, using RNA‐arbitrarily primed‐PCR, we then observed differential regulation of AS mRNA and protein in malignant, compared with normal, OSE cells. A cDNA cancer profiling array with matched normal ovarian and ovarian tumour samples revealed increased expression of AS mRNA in the latter. Moreover, AS protein co‐localised with TNF‐α in ovarian cancer cells, with significantly higher levels of AS in malignant compared with normal ovarian tissue. Increased co‐expression of AS and TNF‐α mRNA was also observed in 2 other epithelial tumours, non‐small cell lung and stomach cancer, compared with normal corresponding tissues. In summary, high levels of AS expression, which may be required for several arginine‐dependent processes in cancer, including the production of nitric oxide, proline, pyrimidines and polyamines, is regulated by TNF‐α and may provide an important molecular pathway linking inflammation and metabolism to ovarian tumorigenesis. © 2007 Wiley‐Liss, Inc.
Finite sample evidence of IV estimators under weak instruments
Authors: Flores‐Lagunes Alfonso 
Published: March 2007

AbstractWe present finite sample evidence on different IV estimators available for linear models under weak instruments; explore the application of the bootstrap as a bias reduction technique to attenuate their finite sample bias; and employ three empirical applications to illustrate and provide insights into the relative performance of the estimators in practice. Our evidence indicates that the random‐effects quasi‐maximum likelihood estimator outperforms alternative estimators in terms of median point estimates and coverage rates, followed by the bootstrap bias‐corrected version of LIML and LIML. However, our results also confirm the difficulty of obtaining reliable point estimates in models with weak identification and moderate‐size samples. Copyright © 2007 John Wiley & Sons, Ltd.
Robust optimal monetary policy in a forward‐looking model with parameter and shock uncertainty
Authors: Giannoni Marc P. 
Published: March 2007

AbstractThis paper characterizes a robust optimal policy rule in a simple forward‐looking model, when the policymaker faces uncertainty about model parameters and shock processes. We show that the robust optimal policy rule is likely to involve a stronger response of the interest rate to fluctuations in inflation and the output gap than is the case in the absence of uncertainty. Thus parameter uncertainty alone does not necessarily justify a small response of monetary policy to perturbations. However, uncertainty may amplify the degree of ‘super‐inertia’ required by optimal monetary policy. We finally discuss the sensitivity of the results to alternative assumptions. Copyright © 2007 John Wiley & Sons, Ltd.
Phlegmasia cerulea dolens
Authors: Bhatt Shweta , Wehbe Charles , Dogra Vikram S. 
Published: March 2007

AbstractPhlegmasia dolens is a rare form of massive venous thrombosis of the lower extremities that is associated with a high degree of morbidity, including venous gangrene, compartment type syndrome, and arterial compromise. We report the sonographic findings in a patient who presented with phlegmasia dolens. © 2007 Wiley Periodicals, Inc. J Clin Ultrasound, 2007
Preoperative localization of parathyroid adenoma with sonography and 99mTc‐sestamibi scintigraphy in primary hyperparathyroidism
Authors: Grosso Ilaria , Sargiotto Antonella , D'Amelio Patrizia , Tamone Cristina , Gasparri Guido , De Filippi Pier Giuseppe , Picciotto Giuseppe , Isaia Giancarlo 
Published: March 2007

AbstractPurpose. To evaluate the sensitivity, specificity, and usefulness of dual‐phase 99mTc‐Sestamibi scintigraphy (SS) and sonography (US) of the neck, alone and in combination, as noninvasive adenoma localizing procedures in patients with primary hyperparathyroidism prior to parathyroidectomy.Methods. We retrospectively analyzed the charts of 79 patients with parathyroid (PT) adenomas and confirmed diagnosis of hyperparathyroidism who were evaluated with SS and US prior to successful parathyroidectomy.Results. Ninety‐three adenomas were removed during bilateral neck exploration. SS alone showed a sensitivity of 76% and a specificity of 79% compared with 89% and 75%, respectively, for US performed after SS on the same day. Combination of the 2 procedures yielded a sensitivity of 89% and a specificity of 90%, with 22% discordant results. The differences in sensitivity and specificity between the 2 techniques alone or in combination were not statistically significant.Conclusions. No benefit was gained from using both SS and US for the preoperative localization of PT adenomas in patients with primary hyperparathyroidism. Each technique can be negatively affected by thyroid enlargment and nodularity. US, when performed by a skilled operator, is a reliable tool for PT adenoma localization. If the US findings are inconclusive, SS should be used. © 2007 Wiley Periodicals, Inc. J Clin Ultrasound, 2007
siRNA delivery by a transferrin‐associated lipid‐based vector: a non‐viral strategy to mediate gene silencing
Authors: Cardoso A. L. C. , Simões S. , de Almeida L. P. , Pelisek J. , Culmsee C. , Wagner E. , Pedroso de Lima M. C. 
Published: March 2007

AbstractBackgroundRNA interference provides a powerful technology for specific gene silencing. Therapeutic applications of small interfering RNA (siRNA) however require efficient vehicles for stable complexation, protection, and extra‐ and intracellular delivery of these nucleic acids. Here, we evaluated the potential of transferrin (Tf)‐associated liposomes for siRNA complexation and gene silencing.MethodsCationic liposomes composed of DOTAP : Cholesterol associated with or without transferrin (Tf) were complexed with siRNA at different lipid/siRNA charge ratios. Complexation and protection of siRNA from enzymatic degradation was assessed with the PicoGreen intercalation assay and gel electrophoresis. Cellular internalization of these siRNA Tf‐lipoplexes was detected by confocal microscopy. Luciferase assay, immunoblot and fluorescence‐activated cell sorting (FACS) analysis were used to evaluate reporter gene silencing in Huh‐7 hepatocarcinoma and U‐373 glioma cells. c‐Jun knockdown in HT‐22 cells was evaluated by quantitative real‐time polymerase chain reaction (RT‐PCR). Cytotoxicity of the siRNA complexes was assessed by Alamar blue, lactate dehydrogenase and MTT assays.ResultsComplexation of siRNA with the cationic liposomes in the presence of Tf results in the formation of stable particles and prevents serum‐mediated degradation. Confocal microscopy showed fast cellular internalization of the Tf‐lipoplexes via endocytosis. In the GFP glioma cells Tf‐lipoplexes showed enhanced gene silencing at minimum toxicity in comparison to Tf‐free lipoplexes. Targeting luciferase in the hepatocarcinoma cell line resulted in more than 70% reduction of luciferase activity, while in HT‐22 cells 50% knockdown of endogenous c‐Jun resulted in a significant protection from glutamate‐mediated toxicity.ConclusionsCationic liposomes associated with Tf form stable siRNA lipoplexes with reduced toxicity and enhanced specific gene knockdown activity compared to conventional lipoplexes. Thus, such formulations may constitute efficient delivery systems for therapeutic siRNA applications. Copyright © 2007 John Wiley & Sons, Ltd.
Identification of transfected cell types following non‐viral gene transfer to the murine lung
Authors: Davies Lee A. , Seguela Claire , Varathalingam Anusha , Cheng Seng H. , Hyde Stephen C. , Gill Deborah R. 
Published: March 2007

AbstractBackgroundIdentification of the cell types transfected following gene transfer is an important factor in the selection of appropriate gene transfer agents (GTAs). Due to the relatively low gene expression mediated by non‐viral GTAs, current methodologies for the detection and identification of transfected cells in the lung have proven insensitive and unreliable. We have investigated the use of the green fluorescent protein (GFP) to identify transfected cells in a mouse lung model.MethodsDirect visualisation of GFP fluorescence in frozen histological sections was used in conjunction with a panel of cell type specific antibodies to investigate the distribution and level of gene expression in mouse lungs following instillation of non‐viral GTAs.ResultsDespite considerable tissue autofluorescence, dose‐dependent expression of GFP was detected following instillation of as little as 25 µg naked plasmid DNA (pDNA). Naked pDNA and pDNA complexed with polyethylenimine appeared to transfect mainly ciliated cells and Clara cells of the conducting airway, whereas expression mediated by pDNA complexed with the cationic lipid GL67 was found predominantly in type I pneumocytes.ConclusionsDirect visualisation of GFP expression was used to detect transfected cell types in the mouse lung. In contrast with observations made using ß‐galactosidase as a reporter, gene expression from several non‐viral GTAs was readily demonstrated and no false GFP‐positive cells were ever detected in untreated lung tissues. Lung delivery of different GTAs resulted in GFP expression in different cell types, confirming the importance of identification of transfected cells when screening and selecting GTAs for disease targets. Copyright © 2007 John Wiley & Sons, Ltd.
Fiber‐knob modifications enhance adenoviral tropism and gene transfer in malignant glioma
Authors: Zheng Sophy , Ulasov Ilya V. , Han Yu , Tyler Matthew A. , Zhu Zeng B. , Lesniak Maciej S. 
Published: March 2007

AbstractBackgroundMalignant gliomas remain refractory to Ad5‐mediated gene therapy due to deficiency of the coxsackie adenovirus receptor on tumor cells. The purpose of this study was to evaluate whether changes in adenoviral tropism can enhance gene transfer in the context of malignant glioma.MethodsWe have identified several receptors that are over‐expressed on tumor cells and created a series of pseudotyped Ad5 vectors that recognize these receptors: Ad5‐RGD which binds αvβ3/αvβ5 integrins; Ad5/3 which contains adenovirus serotype 3 knob and binds to CD46; Ad5‐Sigma which incorporates the reovirus sigma knob and binds to junctional adhesion molecule‐1; and Ad5‐pk7 which contains the polylysine motif and binds heparan sulfate proteoglycans. We also investigated the Ad5‐CAV1 vector, which contains the knob of canine adenovirus type 1, a virus previously shown to infect glioma via an unknown mechanism. In this study, we compared these modified vectors for their ability to promote the expression of luciferase transgene both in vitro and in vivo.ResultsOur results indicate that all five modified vectors attained higher mean luciferase activity vs. control. Among them, Ad5‐CAV1 and Ad5‐pk7 attained the highest transduction efficiency independent of different tumor lines or infection time. Ad5‐Sigma and Ad5‐pk7 also demonstrated the least nonspecific infection in normal human astrocytes. Most importantly, Ad5‐pk7 achieved 1000‐fold increased transgene expression in human glioma xenografts in vivo.ConclusionsThese results indicate that modifications of adenoviral tropism can enhance gene transfer in tumors that are poorly susceptible to adenoviral vectors and warrant further development of Ad5‐pk7 for glioma gene therapy. Copyright © 2007 John Wiley & Sons, Ltd.