bluuebunny/crossref_metadata_2025_split huggingface dataset:
Small molecule antagonists of Tcf4/β‐catenin complex inhibit the growth of HCC cells in vitro and in vivo
Authors: Wei Wei , Chua Mei‐Sze , Grepper Susan , So Samuel 
Published: August 2009

AbstractHepatocellular carcinoma (HCC) is the 5th most common cancer worldwide. It is intrinsically resistant toward standard chemotherapy, making it imperative to develop novel selective chemotherapeutic agents. The Wnt/β‐catenin pathway plays critical roles in development and oncogenesis, and is dysregulated in HCC. Our study aims to evaluate the activity of 3 small molecule antagonists of the Tcf4/β‐catenin complex (PKF118‐310, PKF115‐584 and CGP049090) on HCC cell lines in vitro and in vivo. All 3 chemicals displayed dose‐dependent cytotoxicity in vitro against all 3 HCC cell lines (HepG2, Hep40 and Huh7), but were at least 10 times less cytotoxic to normal hepatocytes (from 3 donors) by using ATP assay. In HepG2 and Huh7 cells, treatment with the antagonists decreased Tcf4/β‐catenin binding capability and transcriptional activity, associated with downregulation of the endogenous Tcf4/ β‐catenin target genes c‐Myc, cyclin D1 and survivin. In HepG2 and Huh7 cells, treatment with the antagonists induced apoptosis and cell cycle arrest at the G1/S phase. All antagonists suppressed in vivo tumor growth in a HepG2 xenograft model, associated with apoptosis and reduced c‐Myc, cyclin D1 and survivin expressions. Our results suggest that these 3 antagonists of the Tcf4/β‐catenin complex are potential chemotherapeutic agents which may offer a pathway specific option for the clinical management of HCC.
Isolation of circulating epithelial and tumor progenitor cells with an invasive phenotype from breast cancer patients
Authors: Lu Janice , Fan Tina , Zhao Qiang , Zeng Wei , Zaslavsky Eva , Chen John J. , Frohman Michael A. , Golightly Marc G. , Madajewicz Stefan , Chen Wen‐Tien 
Published: August 2009

AbstractRecent research advances show that tumor cell intravasation (entry into the circulation) and metastasis occur very early in breast cancer progression. Clinical studies also illustrate the potential importance of detection of circulating tumor cells (CTCs) in outcomes of patients with metastatic breast cancer. Whether these cells exhibit the invasiveness and express tumor stem or progenitor markers, hallmark of the metastatic phenotype, is less well characterized. To detect CTCs with the invasive phenotype and to explore their molecular features, we applied a functional cell separation method, called collagen adhesion matrix (CAM) assay, as enrichment and identification steps. The CAM‐coated device successfully recovered tumor cells spiked in 1 ml of blood with a 54% ± 9% (n = 18) recovery rate and 0.5–35% purity, and detected invasive tumor cells in 10/10 blood samples (100% yield) from patients with metastatic breast cancer with a range of 18–256 CTCs/ml and average of 126 ± 25 (mean ± SD) CTCs/ml. CTCs were detected in blood samples of 28/54 (52%) Stage I–III breast cancer patients with a mean count of 61 CTCs/ml. Furthermore, the relative frequency of these cells correlated to the staging, lymph node‐status and survival of patients with early stage breast cancer. CAM‐captured cells were capable of propagation in culture. Gene expression and multiplex flow cytometric analyses on CAM‐captured cells demonstrated the existence of distinct populations of CTCs including these of epithelial lineage and stem or progenitor cells. Thus, CAM‐initiated CTC detection provides advantages for examining invasiveness and tumor progenitor phenotypes.
A highly stable whole‐cell biocatalyst for the enantioselective synthesis of optically active alpha‐hydroxy acids
Authors: Guo Jinling , Mu Xiaoqing , Zheng Changge , Xu Yan 
Published: August 2009

AbstractBACKGROUND: Biocatalysts have gained increasing attention because of their inherent advantages over chemical catalysts. However, the poor operational stability has always prevented their broad application. In this study, (R)‐mandelic acid was chosen as a model compound of alpha‐hydroxy acids. The objective was to obtain a new biocatalyst with desired operational stability for the preparation of (R)‐mandelic acid as well as other optically pure alpha‐hydroxy acids of pharmaceutical importance.RESULTS: Using a two‐step screening strategy, Saccharomyces ellipsoideus GIM2.105 was selected as an effective biocatalyst with high enantioselectivity and remarkable operational stability. After 20 cycles of reuse, whole cells of S. ellipsoideus GIM2.105 maintained its activity, and no obvious decrease in conversion or enantiomeric excess (ee) was observed. Furthermore, effects of various reaction parameters, including pH, temperature, co‐substrate (type, concentration), substrate concentration and reaction time, on the bioreduction were studied. Under optimal conditions, (R)‐mandelic acid and four substituted aromatic (R)‐alpha‐hydroxy acids were prepared in high ee (95–>99%) and good conversion (>90%).CONCLUSION: The high enantioselectivity, remarkable operational stability and mild reaction conditions showed S. ellipsoideus GIM2.105 to be an economical biocatalyst with great industrial application potential for the production of optically active alpha‐hydroxy acids. Copyright © 2009 Society of Chemical Industry
Tip‐induced heating in apertureless near‐field optics
Authors: Malkovskiy A. V. , Malkovsky V. I. , Kisliuk A. M. , Barrios C. A. , Foster M. D. , Sokolov A. P. 
Published: August 2009

AbstractTip‐enhanced Raman spectroscopy is considered a promising technique for imaging with nanoscale lateral resolution. However, its developments and use face many problems. In this paper we provide insight into the level of sample heating by the laser light in the presence of a metal‐coated atomic force microscope (AFM) tip. The heating is attributed to the presence of an optical field enhanced by the tip. Sample temperatures were estimated using measurements of the ratio of the Stokes and anti‐Stokes signals from a thin 50‐nm sample on an Al substrate. A correlation between the heating and optical properties of the tips is established. The results demonstrate significant tip‐induced heating (100 K and more) even at very low laser power. Copyright © 2009 John Wiley & Sons, Ltd.
Global benefit–risk analysis of adjunctive aripiprazole in the treatment of patients with major depressive disorder
Authors: Wisniewski, PhD Stephen R. , Chen, PhD Chi‐Chang , Kim, MD, MBA Edward , Kan, PhD Hong J. , Guo, PhD Zhenchao , Carlson, PhD Berit X. , Tran, Pharm D, BCPP Quynh‐Van , Pikalov, MD, PhD Andrei 
Published: August 2009

AbstractObjectiveThis study quantified the overall merit of adjunctive aripiprazole in major depressive disorder (MDD).MethodsGlobal benefit–risk (GBR) analysis quantified the benefit and risk differences between adjunctive aripiprazole and antidepressant (ADT) monotherapy. Three hundred and fifty six patients receiving ADT monotherapy and 366 patients receiving ADT and adjunctive aripiprazole (2–20 mg/day) were included. Efficacy measures included the Montgomery–Åsberg depression rating scale (MADRS) Total score response (≥50% reduction) and remission (response plus Total score ≤ 10). Treatment‐emergent adverse events were classified by severity. GBR ratio measures evaluated the relative benefit of adjunctive aripiprazole. Logistic regression models tested the effect of adjunctive aripiprazole on GBR and were used to identify predictors of net benefit and potential factors affecting the adjunctive aripiprazole treatment effect.ResultsFor MADRS‐defined response and remission, the relative gain of adjunctive aripiprazole versus ADT monotherapy was 1.46 (p = 0.044) and 1.43 (p = 0.085), respectively. Gender, current escitalopram, duration of current episode, and baseline body mass index are potential factors affecting the adjunctive aripiprazole treatment effect.ConclusionsCompared with ADT monotherapy, adjunctive aripiprazole was associated with an improved benefit–risk profile in MDD. Copyright © 2009 John Wiley & Sons, Ltd.
Temporal trends in anti‐diabetes drug use in tricare following safety warnings in 2007 about rosiglitazone
Authors: Stewart Kate A. , Natzke Brenda M. , Williams Thomas , Granger Elder , Casscells S. Ward , Croghan Thomas W. 
Published: August 2009

AbstractPurposeTo describe utilization patterns for anti‐diabetes medications among a cohort of diabetes patients in the Military Health System (MHS) before and after warnings about rosiglitazone issued in May 2007.MethodsWe used segmented regression analysis to compare changes in the level and trend of rosiglitazone utilization and use of other anti‐diabetes therapies in the period prior to the drug warnings (between April 2006 and May 2007) and the period after the warnings were issued (between October 2007 and May 2008).ResultsThe level and trend of rosiglitazone use changed after the highly publicized warnings. The number of prescriptions filled fell by almost 7000 after the warning (p < 0.001). The number of prescriptions filled for pioglitazone, sulfonylureas, and other diabetes drugs increased significantly after the warnings (p < 0.05 in all models). Overall, the level and trend of filled prescriptions per month for all anti‐diabetic drugs did not significantly change after the warnings.ConclusionsUtilization patterns changed in response to warnings about rosiglitazone. While overall utilization of anti‐diabetic drugs did not change, further study is needed to determine the associated health outcomes. Copyright © 2009 John Wiley & Sons, Ltd.
Differential expression of cell surface proteins in human bone marrow mesenchymal stem cells cultured with or without basic fibroblast growth factor containing medium
Authors: Lee Sang Kwang , Kim Yongtae , Kim Sung‐Soo , Lee Jeong Hwa , Cho Kun , Lee Sang Sook , Lee Zee‐Won , Kwon Kyung‐Hoon , Kim Young Hye , Suh‐Kim Haeyoung , Yoo Jong Shin , Park Young Mok 
Published: August 2009

AbstractMesenchymal stem cells (MSCs) are multipotent cells, which have the capability to differentiate into various mesenchymal tissues such as bone, cartilage, fat, tendon, muscle, and marrow stroma. However, they lose the capability of multi‐lineage differentiation after several passages. It is known that basic fibroblast growth factor (bFGF) increases growth rate, differentiation potential, and morphological changes of MSCs in vitro. In this report, we have used 2‐DE coupled to MS to identify differentially expressed proteins at the cell membrane level in MSCs growing in bFGF containing medium. The cell surface proteins isolated by the biotin–avidin affinity column were separated by 2‐DE in triplicate experiments. A total of 15 differentially expressed proteins were identified by quadrupole‐time of flight tandem MS. Nine of the proteins were upregulated and six proteins were downregulated in the MSCs cultured with bFGF containing medium. The expression level of three actin‐related proteins, F‐actin‐capping protein subunit alpha‐1, actin‐related protein 2/3 complex subunit 2, and myosin regulatory light chain 2, was confirmed by Western blot analysis. The results indicate that the expression levels of F‐actin‐capping protein subunit alpha‐1, actin‐related protein 2/3 complex subunit 2, and myosin regulatory light chain 2 are important in bFGF‐induced morphological change of MSCs.
Reverse‐phase protein arrays for application‐orientated cancer research
Authors: Korf Ulrike , Löbke Christian , Sahin Özgür , Haller Florian , Sültmann Holger , Arlt Dorit , Poustka Annemarie 
Published: August 2009

AbstractA detailed and quantitative analysis of disease‐relevant signaling will greatly contribute to our understanding of tumorigenesis and cancer progression, and thus open new strategies for drug discovery. However, throughput and sensitivity of currently established methods available for proteome profiling do not comply with the needs of clinical research such as high sample capacity and low sample consumption. Protein microarrays emerged as a promising alternative to analyze the abundance of proteins and their phosphorylation status on a high‐throughput level. Here we summarize recent methodological advancements in the field of reverse‐phase protein arrays and demonstrate their potential for clinical research as well as for in vitro applications.
Fabrication of Flexible Metal‐Nanoparticle Films Using Graphene Oxide Sheets as Substrates
Authors: Xu Chao , Wang Xin 
Published: August 2009

AbstractGraphene‐based sheets that possess a unique nanostructure and a variety of fascinating properties are appealing as promising nanoscale building blocks of new composites. Herein, graphene oxide sheets are used as the nanoscale substrates for the formation of silver‐nanoparticle films. These silver‐nanoparticle films assembled on graphene oxide sheets are flexible and can form stable suspensions in aqueous solutions. They can also be easily processed, forming macroscopic films with high reflectivity. Raman signals of graphene oxide in such hybrid films are increased by the attached silver nanoparticles, displaying surface‐enhanced Raman scattering activity. The degree of enhancement can be adjusted by varying the quantity of silver nanoparticles on the graphene oxide sheets.
Clinical and Pathologic Differences Between BRCA1‐, BRCA2‐, and Non‐BRCA‐Associated Breast Cancers in a Multiracial Developing Country
Authors: Yip Cheng‐Har , Taib N. A. , Choo W. Y. , Rampal S. , Thong M. K. , Teo S. H. 
Published: August 2009

AbstractBackgroundMutations in BRCA1 and BRCA2 confer an increased risk to breast and other cancers, but to date there have only been limited numbers of studies of BRCA1‐ and BRCA2‐associated cancers among Asians. Malaysia is a multiracial country with three main races: Malays, Chinese, Indians. We determined whether tumor pathologic features and clinical features differ in patients with and without BRCA mutations in this Asian population.MethodsWe conducted a retrospective review of the medical records of 152 women with breast cancer who underwent genetic testing for BRCA mutations. The patients self‐reported ethnicity, age at onset, and clinical stage at diagnosis and tumor pathology were reviewed.ResultsA total of 31 patients carried germline deleterious mutations (16 BRCA1, 15 BRCA2). We found that tumors in BRCA1 carriers were more likely to be estrogen receptor (ER)‐negative and progesterone receptor (PR)‐negative. HER2 was more likely to be negative in both BRCA1 and BRCA2 subjects compared with non‐BRCA subjects. We found a strong association between triple‐negative status and BRCA1 carriers. In addition, tumors in BRCA1 carriers were more likely to be higher grade than those in BRCA2 and non‐BRCA carriers; but the difference was not statistically significant.ConclusionsThese results suggest that tumors associated with BRCA1 mutations are distinct from those of BRCA2‐associated and non‐BRCA‐associated breast cancers, and that the tumors associated with BRCA2 mutations are similar to the non‐BRCA‐associated breast cancers. Further studies are required to determine if the prognosis is different in each of these groups and the best management strategy for each group.
Gastric Emptying Function in Patients 5 Years After Pylorus‐Preserving Distal Gastrectomy With or Without Preserving Pyloric and Hepatic Branches of the Vagal Nerve for Early Gastric Cancer
Authors: Tomita Ryouichi 
Published: August 2009

AbstractBackgroundTo clarify the significance of preserving pyloric and hepatic branches of the vagal nerve (PHV) after pylorus preserving distal gastrectomy (PPG) for early gastric cancer, the author investigated the postgastrectomy syndrome and gastric emptying function at 5 years in PPG patients with or without preserving the PHV.MethodsA total of 18 subjects (mucosal cancers) who underwent PPG with D1 lymph node dissection and preserving the PHV; they comprised group A—12 men and 6 women aged 38–68 years (mean 58.9 years). They were interviewed to inquire about gastrointestinal symptom (appetite, weight loss, gastric fullness, reflux esophagitis, early dumping syndrome) and then were compared with 24 PPG patients (submucosal cancers) with D2 lymph node dissection without preserving the PHV (group B—16 men and 8 women aged 33 to 69 years, mean 60.1 years). Esophagogastric endoscopy, abdominal ultrasonography, and gastric emptying function tests (GET) were undertaken, the latter by both radioisotope (solid diet) and acetaminophen (liquid diet) methods.ResultsThere were no differences in the postoperative gastrointestinal symptoms, endoscopic reflux esophagitis, or endoscopic mucosal edema and redness (gastropathy) between groups A and B. However, more cholecystolithiasis (gallbladder stones) was found in group A than in group B, with the difference being significant (P < 0.0391). The GET for solid diet and liquid diet were the almost same among groups A and B.ConclusionsThere were no significant differences in the postoperative QOL and GET between PPG patients with preserving PHV and those without preserving PHV. Cholecystolithiasis was only found in patients without preserving PHV.
A Meta‐Analysis of Randomized, Controlled Trials Assessing the Prophylactic Use of Ceftriaxone. A Study of Wound, Chest, and Urinary Infections
Authors: Woodfield J. C. , Beshay N. , van Rij A. M. 
Published: August 2009

AbstractBackgroundCeftriaxone is an effective prophylactic antibiotic. However, there is no consensus about whether ceftriaxone should be used as a first‐line antibiotic for the prevention of incisional surgical site infection (SSI). Its role in preventing urinary tract infection (UTI) and pneumonia also is controversial.MethodsA meta‐analysis of randomized, controlled trials assessing the prophylactic use of ceftriaxone between 1983 and 2005 was performed. Medline, Embase, and Cochrane registers were reviewed. Additional references, review papers, and proceedings from meetings were searched. The Jadad score was used to assess study quality. A meta‐analysis with sensitivity analyses was performed for SSI, UTI, and pneumonia.ResultsOf 231 reviewed papers, 90 were included. Ceftriaxone prophylaxis was superior to other antibiotics in each category. Sixty‐one studies assessed the prevention of SSI (odds ratio (OR), 0.68; 95% confidence interval (CI), 0.53–0.7, p < 0.001; Cochran’s Q statistic, p = 0.93). The difference was greatest for abdominal surgery. There was no difference for cardiac surgery. Thirty‐five studies assessed the prevention of UTI (OR 0.53; 95% CI 0.43–0.63, p = 0; Cochran’s Q statistic, p = 0.97). The difference was greatest in obstetric and gynecological and colorectal surgery. Thirty‐seven studies assessed the prevention of pneumonia (OR 0.66; 95% CI 0.54–0.81, p = 0; Cochran’s Q statistic, p = 0.65). The difference was greatest in upper abdominal surgery.ConclusionsThe meta‐analysis confirms that prophylactic ceftriaxone is more effective than most other prophylactic antibiotics. This reduces SSI, UTI, and pneumonia in procedures where there is an increased risk of these infections. In such procedures, the data support using ceftriaxone as a first‐line prophylactic antibiotic.
Thick Melanoma: Prognostic Value of Positive Sentinel Nodes
Authors: Vermeeren Lenka , van der Ent Fred W. C. , Sastrowijoto Prapto S. H. , Hulsewé Karel W. E. 
Published: August 2009

AbstractBackgroundSentinel lymph node biopsy (SNB) is a widely accepted procedure used to accurately stage patients with melanoma. Its value in patients with thick melanoma (Breslow thickness >4 mm) is reason for discussion because of the generally poor prognosis of these patients. The purpose of this study was to report on the incidence of SNB positivity in patients with thick melanoma and to analyze the prognostic value of SNB in these patients.MethodsThe prospective database of 248 patients with cutaneous melanoma, who underwent SNB in the Maaslandhospital Sittard between January 1994 and August 2007, was reviewed and completed. In 31 patients, SNB was performed for a thick melanoma. We analyzed survival (Kaplan–Meier) and survival differences (log‐rank) in this group.ResultsIn 64.5% of the patients with a thick melanoma, the SNB was positive. In our patients, SNB result was the only predictor for overall survival in patients with a thick melanoma (P = 0.045).ConclusionsTo be accurately informed about a patient’s prognosis and to decide whether subsequent completion lymph node dissection is indicated, SNB should not be omitted in patients with a primary thick melanoma.
Cardiovascular Risk in Patients with Nonfunctional Adrenal Incidentaloma: Myth or Reality?
Authors: Erbil Yesim , Ozbey Nese , Barbaros Umut , Unalp Haluk Recai , Salmaslıoglu Artur , Özarmagan Selçuk 
Published: August 2009

AbstractBackgroundIt is not clear whether nonfunctional adrenal incidentaloma (NFA) increases the risk of atherosclerosis and metabolic syndrome or whether this type of adrenal tumor has been found more frequently in patients with cardiometabolic risk factors. We aimed to determine the effects of NFA on cardiometabolic risk factors and endothelial function and to compare the patients with a 1:1 cardiometabolic risk factor matched control group.MethodsThirty‐five patients with NFA were studied, and 35 body mass index‐, age‐, and sex‐matched subjects were regarded as group 2 controls. Thirty‐five cardiometabolic risk factors–matched subjects were then regarded as group 3 controls.ResultsPatients with NFA had significantly lower flow‐mediated dilation (FMD)—a parameter for endothelial function—measurements compared with groups 2 and 3 (7.1 ± 2.9% vs. 12.9 ± 3.8% and 13.5 ± 4.5%; P < 0.02). Frequency of metabolic syndrome was also significantly higher in NFA patients than in control groups 2 and 3 (31.4, 5.7, and 20.0%, respectively; P < 0.05). Age (Odds Ratio [OR] = 2.9), total cholesterol (OR = 2.3), and presence of adrenal incidentaloma (OR = 10) were significant independent predictors of lower FMD (P < 0.05 for all).ConclusionsPatients with NFA have increased prevalence of metabolic syndrome and impaired endothelial function compared with 1:1 cardiometabolic risk factor–matched controls.
What ought probably means, and why you can’t detach it
Authors: Finlay Stephen 
Published: August 2009

AbstractSome intuitive normative principles raise vexing ‘detaching problems’ by their failure to license modus ponens. I examine three such principles (a self-reliance principle and two different instrumental principles) and recent stategies employed to resolve their detaching problems. I show that solving these problems necessitates postulating an indefinitely large number of senses for ‘ought’. The semantics for ‘ought’ that is standard in linguistics offers a unifying strategy for solving these problems, but I argue that an alternative approach combining an end-relational theory of normativity with a comparative probabilistic semantics for ‘ought’ provides a more satisfactory solution.
Binary Mixtures of SH- and CH3-Terminated Self-Assembled Monolayers to Control the Average Spacing Between Aligned Gold Nanoparticles
Authors: Rezaee Asad , Pavelka Laura C , Mittler Silvia 
Published: August 2009

Abstract
This paper presents a method to control the average spacing between organometallic chemical vapor deposition (OMCVD) grown gold nanoparticles (Au NPs) in a line. Focused ion beam patterned CH3-terminated self-assembled monolayers are refilled systematically with different mixtures of SH- and CH3-terminated silanes. The average spacing between OMCVD Au NPs is demonstrated systematically to decrease by increasing the v/v% ratio of the thiols in the binary silane mixtures with SH- and CH3-terminated groups.