bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishment of Perineural Invasion Models and Analysis of Gene Expression Revealed an Invariant Chain (CD74) as a Possible Molecule Involved in Perineural Invasion in Pancreatic Cancer
Authors: Koide Norimasa , Yamada Taketo , Shibata Rie , Mori Taisuke , Fukuma Mariko , Yamazaki Ken , Aiura Koichi , Shimazu Motohide , Hirohashi Setsuo , Nimura Yuji , Sakamoto Michiie 
Published: April 2006

AbstractPurpose: Perineural invasion causes frequent local recurrence even after resection and a poor prognosis for pancreatic cancer. We established perineural invasion models and analyzed the molecular mechanism of perineural invasion in pancreatic cancer.Experimental Design: Seven pancreatic cancer cell lines with or without human peripheral nerves were s.c. implanted in nonobese diabetes/severe combined immunodeficient mice. We compared expression profiles among high and low perineural invasion cell lines by using an oligonucleotide microarray. We examined up-regulation of the invariant chain (CD74) in high perineural invasion cell lines in mRNA and protein levels and surgical cases immunohistochemically.Results: Four of seven pancreatic cancer cell lines (CaPan1, CaPan2, CFPAC, and MPanc96) showed perineural invasion to s.c. transplanted human peripheral nerves. Moreover, CaPan1 and CaPan2 (high perineural invasion group) also resulted in a high frequency of perineural invasion to mouse s.c. peripheral nerves, whereas three pancreatic cancer cell lines HPAFII, AsPC1, and Panc1 (low perineural invasion group) did not show perineural invasion to either human or mouse nerves. We identified 37 up-regulated genes and 12 down-regulated genes in the high perineural invasion group compared with the low perineural invasion group. Among them, CD74 was up-regulated in the high perineural invasion group in mRNA and protein levels. Furthermore, immunohistochemical expression of CD74 in clinical cases revealed its significant overexpression in pancreatic cancer with perineural invasion (P &lt; 0.008).Conclusions: This is the first report of perineural invasion models using human pancreatic cancer cell lines. In combination with gene expression profiling, it was indicated that CD74 could be a candidate molecule involved in perineural invasion. These models provide new approaches for study of perineural invasion in pancreatic cancer.
The Bisphosphonate Olpadronate Inhibits Skeletal Prostate Cancer Progression in a Green Fluorescent Protein Nude Mouse Model
Authors: Yang Meng , Burton Doug W. , Geller Jack , Hillegonds Darren J. , Hastings Randolph H. , Deftos Leonard J. , Hoffman Robert M. 
Published: April 2006

Abstract
Purpose: Metastatic bone disease is one of the major causes of morbidity and mortality in prostate cancer patients. Bisphosphonates are currently used to inhibit bone resorption and reduce tumor-induced skeletal complications. More effective bisphosphonates would enhance their clinical value.
Experimental Design: We tested several bisphosphonates in a green fluorescent protein (GFP)–expressing human prostate cancer nude mouse model. The in vivo effects of four bisphosphonates, including pamidronate, etidronic acid, and olpadronate, on bone tumor burden in mice intratibially inoculated with PC-3-GFP human prostate cancer cells were visualized by whole-body fluorescence imaging and X-ray.
Results: The PC-3-GFP cells produced extensive bone lesions when injected into the tibia of immunocompromised mice. The skeletal progression of the PC-3-GFP cell growth was monitored by GFP fluorescence and the bone destruction was evaluated by X-ray. We showed that 3,3-dimethylaminopropane-1-hydroxy-1,1-diphosphonic acid (olpadronate) was the most effective bisphosphonate treatment in reducing tumor burden as assessed by GFP imaging and radiography. The GFP tumor area and X-ray score significantly correlated. Reduced tumor growth in the bone was accompanied by reduced serum calcium, parathyroid hormone–related protein, and osteoprotegerin.
Conclusions: The serum calcium, parathyroid hormone–related protein, and osteoprotegerin levels were significantly correlated with GFP area and X-ray scores. Treatment with olpadronate reduced tumor growth in the bone measured by GFP and X-ray imaging procedures. Imaging of GFP expression enables monitoring of tumor growth in the bone and the GFP results complement the X-ray assessment of bone disease. The data in this report suggest that olpadronate has potential as an effective inhibitor of the skeletal progression of clinical prostate cancer.
Coexpression of Actin-Related Protein 2 and Wiskott-Aldrich Syndrome Family Verproline-Homologous Protein 2 in Adenocarcinoma of the Lung
Authors: Semba Seitaro , Iwaya Keiichi , Matsubayashi Jun , Serizawa Hiromi , Kataba Hiroaki , Hirano Takashi , Kato Harubumi , Matsuoka Takeshi , Mukai Kiyoshi 
Published: April 2006

Abstract
Purpose: Highly invasive and metastatic cancer cells, such as adenocarcinoma of the lung cells, form irregular protrusions by assembling a branched network of actin filaments. In mammalian cells, the actin-related protein 2 and 3 (Arp2/3) complex initiates actin assembly to form lamellipodial protrusions by binding to Wiskott-Aldrich syndrome (WASP)/WASP family verproline-homologous protein 2 (WAVE2). In this study, colocalization of Arp2 and WAVE2 in adenocarcinoma of the lung was investigated to elucidate its prognostic value.
Experimental Design: Immunohistochemical staining of Arp2 and WAVE2 was done on mirror sections of 115 adenocarcinomas of the lung from pathologic stage IA to IIIA classes. Kaplan-Meier disease-free survival and overall survival curves were analyzed to determine the prognostic significance of the coexpression of Arp2 and WAVE2.
Results: Immunoreactivity for both Arp2 and WAVE2 was detected in the same cancer cells in 78 (67.8%) of the 115 lung cancer specimens. The proportion of cancer cells expressing both Arp2 and WAVE2 was significantly higher in cases with lymph-node metastasis (P = 0.0046), and significantly lower in bronchioloalveolar carcinomas (P &lt; 0.0001). The patients whose cancer cells coexpressed them had a shorter disease-free survival time (P &lt; 0.0001) and overall survival time (P &lt; 0.0001). Multivariate Cox regression analysis revealed that coexpression of Arp2 and WAVE2 is an independent risk factor for tumor recurrence.
Conclusions: Coexpression of Arp2 and WAVE2 is correlated with poorer patient outcome, and may be involved in the mechanism of cancer metastasis.
Optimization of Patient Selection for Gefitinib in Non–Small Cell Lung Cancer by Combined Analysis of Epidermal Growth Factor Receptor Mutation, K-ras Mutation, and Akt Phosphorylation
Authors: Han Sae-Won , Kim Tae-You , Jeon Yoon Kyung , Hwang Pil Gyu , Im Seock-Ah , Lee Kyung-Hun , Kim Jee Hyun , Kim Dong-Wan , Heo Dae Seog , Kim Noe Kyeong , Chung Doo Hyun , Bang Yung-Jue 
Published: April 2006

Abstract
Purpose: Mutations in epidermal growth factor receptor (EGFR) are strongly predictive of gefitinib efficacy in non–small-cell lung cancer. However, the presence of EGFR mutant nonresponses and nonmutant responses points out the need for more comprehensive analysis.
Patients and Methods: For 69 non–small-cell lung cancer patients treated with gefitinib, we have extended our analysis to EGFR gene copy number by fluorescence in situ hybridization, mutations in K-ras, HER2, and exon 20 of EGFR by direct sequencing, and phosphatase and tensin homologue expression by immunohistochemistry, in addition to EGFR exons 18, 19, and 21, and phosphorylations of Akt and extracellular signal–regulated kinase reported previously.
Results: EGFR mutation and high gene copy number were associated with better objective response in univariate analysis. However, only gefitinib-sensitive EGFR mutation was independently predictive of both response (P = 0.011) and survival (P = 0.002) in multivariate analysis. No patients with K-ras mutation, including two EGFR mutants, showed response. In EGFR nonmutants, patients with either K-ras mutation or p-Akt overexpression exhibited poor response and time-to-progression whereas patients with high gene copy number tended to have better outcomes in univariate analysis. In multivariate analysis of time-to-progression in EGFR nonmutants, K-ras mutation or p-Akt overexpression was associated with shorter time-to-progression (P = 0.017). No patient with HER2 mutation showed response to gefitinib. Reduced phosphatase and tensin homologue expression was not associated with gefitinib sensitivity.
Conclusion: Gefitinib-sensitive EGFR mutation is the single most important predictor of gefitinib sensitivity. In addition to EGFR mutation, K-ras mutation and Akt phosphorylation aid in better prediction of gefitinib responsiveness in non–small-cell lung cancer.
An Observational Study of Mesoscale Convective Systems with Heavy Rainfall over the Korean Peninsula
Authors: Kim Hyung Woo , Lee Dong Kyou 
Published: April 2006

Abstract
A heavy rainfall event induced by mesoscale convective systems (MCSs) occurred over the middle Korean Peninsula from 25 to 27 July 1996. This heavy rainfall caused a large loss of life and property damage as a result of flash floods and landslides. An observational study was conducted using Weather Surveillance Radar-1988 Doppler (WSR-88D) data from 0930 UTC 26 July to 0303 UTC 27 July 1996. Dominant synoptic features in this case had many similarities to those in previous studies, such as the presence of a quasi-stationary frontal system, a weak upper-level trough, sufficient moisture transportation by a low-level jet from a tropical storm landfall, strong potential and convective instability, and strong vertical wind shear. The thermodynamic characteristics and wind shear presented favorable conditions for a heavy rainfall occurrence. The early convective cells in the MCSs initiated over the coastal area, facilitated by the mesoscale boundaries of the land–sea contrast, rain–no rain regions, saturated–unsaturated soils, and steep horizontal pressure and thermal gradients. Two MCSs passed through the heavy rainfall regions during the investigation period. The first MCS initiated at 1000 UTC 26 July and had the characteristics of a supercell storm with small amounts of precipitation, the appearance of a mesocyclone with tilting storm, a rear-inflow jet at the midlevel of the storm, and fast forward propagation. The second MCS initiated over the upstream area of the first MCS at 1800 UTC 26 July and had the characteristics of a multicell storm, such as a broken areal-type squall line, slow or quasi-stationary backward propagation, heavy rainfall in a concentrated area due to the merging of the convective storms, and a stagnated cluster system. These systems merged and stagnated because their movement was blocked by the Taebaek Mountain Range, and they continued to develop because of the vertical wind shear resulting from a low-level easterly inflow.
SSeCKS/Gravin/AKAP12 attenuates expression of proliferative and angiogenic genes during suppression of v-Src-induced oncogenesis
Authors: Liu Yongzhong , Gao Lingqiu , Gelman Irwin H 
Published: April 2006

Abstract

Background
SSeCKS is a major protein kinase C substrate with kinase scaffolding and metastasis-suppressor activity whose expression is severely downregulated in Src- and Ras-transformed fibroblast and epithelial cells and in human prostate, breast, and gastric cancers. We previously used NIH3T3 cells with tetracycline-regulated SSeCKS expression plus a temperature-sensitive v-Src allele to show that SSeCKS re-expression inhibited parameters of v-Src-induced oncogenic growth without attenuating in vivo Src kinase activity.

Methods
We use cDNA microarrays and semi-quantitative RT-PCR analysis to identify changes in gene expression correlating with i) SSeCKS expression in the absence of v-Src activity, ii) activation of v-Src activity alone, and iii) SSeCKS re-expression in the presence of active v-Src.

Results
SSeCKS re-expression resulted in the attenuation of critical Src-induced proliferative and pro-angiogenic gene expression including Afp, Hif-1α, Cdc20a and Pdgfr-β, and conversely, SSeCKS induced several cell cycle regulatory genes such as Ptpn11, Gadd45a, Ptplad1, Cdkn2d (p19), and Rbbp7.

Conclusion
Our data provide further evidence that SSeCKS can suppress Src-induced oncogenesis by modulating gene expression downstream of Src kinase activity.
Predicting inpatient violence using an extended version of the Brøset-Violence-Checklist: instrument development and clinical application
Authors: Abderhalden Christoph , Needham Ian , Dassen Theo , Halfens Ruud , Haug Hans-Joachim , Fischer Joachim 
Published: April 2006

Abstract

Background
Patient aggression is a common problem in acute psychiatric wards and calls for preventive measures. The timely use of preventive measures presupposes a preceded risk assessment. The Norwegian Brøset-Violence-Checklist (BVC) is one of the few instruments suited for short-time prediction of violence of psychiatric inpatients in routine care. Aims of our study were to improve the accuracy of the short-term prediction of violence in acute inpatient settings by combining the Brøset-Violence-Checklist (BVC) with an overall subjective clinical risk-assessment and to test the application of the combined measure in daily practice.

Method
We conducted a prospective cohort study with two samples of newly admitted psychiatric patients for instrument development (219 patients) and clinical application (300 patients). Risk of physical attacks was assessed by combining the 6-item BVC and a 6-point score derived from a Visual Analog Scale. Incidents were registered with the Staff Observation of Aggression Scale-Revised SOAS-R. Test accuracy was described as the area under the receiver operating characteristic curve (AUCROC).

Results
The AUCROC of the new VAS-complemented BVC-version (BVC-VAS) was 0.95 in and 0.89 in the derivation and validation study respectively.

Conclusion
The BVC-VAS is an easy to use and accurate instrument for systematic short-term prediction of violent attacks in acute psychiatric wards. The inclusion of the VAS-derived data did not change the accuracy of the original BVC.
Membrane-associated heparan sulfate is not required for rAAV-2 infection of human respiratory epithelia
Authors: Boyle Michael P , Enke Raymond A , Reynolds Jeffrey B , Mogayzel Peter J , Guggino William B , Zeitlin Pamela L 
Published: April 2006

Abstract

Background
Adeno-associated virus type 2 (AAV-2) attachment and internalization is thought to be mediated by host cell membrane-associated heparan sulfate proteoglycans (HSPG). Lack of HSPG on the apical membrane of respiratory epithelial cells has been identified as a reason for inefficient rAAV-2 infection in pulmonary applications in-vivo. The aim of this investigation was to determine the necessity of cell membrane HSPG for efficient infection by rAAV-2.

Results
Rates of transduction with rAAV2-CMV-EGFP3 in several different immortalized airway epithelial cell lines were determined at different multiplicities of infection (MOI) before and after removal of membrane HSPG by heparinase III. Removal of HSPG decreased the efficacy of infection with rAAV2 by only 30–35% at MOI ≤ 100 for all of respiratory cell lines tested, and had even less effect at an MOI of 1000. Studies in mutant Chinese Hamster Ovary cell lines known to be completely deficient in surface HSPG also demonstrated only moderate effect of absence of HSPG on rAAV-2 infection efficacy. However, mutant CHO cells lacking all membrane proteoglycans demonstrated dramatic reduction in susceptibility to rAAV-2 infection, suggesting a role of membrane glycosaminoglycans other than HSPG in mediating rAAV-2 infection.

Conclusion
Lack of cell membrane HSPG in pulmonary epithelia and other cell lines results in only moderate decrease in susceptibility to rAAV-2 infection, and this decrease may be less important at high MOIs. Other cell membrane glycosaminoglycans can play a role in permitting attachment and subsequent rAAV-2 internalization. Targeting alternative membrane glycosaminoglycans may aid in improving the efficacy of rAAV-2 for pulmonary applications.
Early identification of intensive care unit-acquired infections with daily monitoring of C-reactive protein: a prospective observational study
Authors: Póvoa Pedro , Coelho Luís , Almeida Eduardo , Fernandes Antero , Mealha Rui , Moreira Pedro , Sabino Henrique 
Published: April 2006

Abstract
Introduction
Manifestations of sepsis are sensitive but are poorly specific of infection. Our aim was to assess the value of daily measurements of C-reactive protein (CRP), temperature and white cell count (WCC) in the early identification of intensive care unit (ICU)-acquired infections.

Methods
We undertook a prospective observational cohort study (14 month). All patients admitted for ≥72 hours (n = 181) were divided into an infected (n = 35) and a noninfected group (n = 28). Infected patients had a documented ICU-acquired infection and were not receiving antibiotics for at least 5 days before diagnosis. Noninfected patients never received antibiotics and were discharged alive. The progression of CRP, temperature and WCC from day -5 to day 0 (day of infection diagnosis or of ICU discharge) was analyzed. Patients were divided into four patterns of CRP course according to a cutoff value for infection diagnosis of 8.7 mg/dl: pattern A, day 0 CRP >8.7 mg/dl and, in the previous days, at least once below the cutoff; pattern B, CRP always >8.7 mg/dl; pattern C, day 0 CRP ≤8.7 mg/dl and, in the previous days, at least once above the cutoff; and pattern D, CRP always ≤8.7 mg/dl.

Results
CRP and the temperature time-course showed a significant increase in infected patients, whereas in noninfected it remained almost unchanged (P < 0.001 and P < 0.001, respectively). The area under the curve for the maximum daily CRP variation in infection prediction was 0.86 (95% confidence interval: 0.752–0.933). A maximum daily CRP variation >4.1 mg/dl was a good marker of infection prediction (sensitivity 92.1%, specificity 71.4%), and in combination with a CRP concentration >8.7 mg/dl the discriminative power increased even further (sensitivity 92.1%, specificity 82.1%). Infection was diagnosed in 92% and 90% of patients with patterns A and B, respectively, and in only two patients with patterns C and D (P < 0.001).

Conclusion
Daily CRP monitoring and the recognition of the CRP pattern could be useful in the prediction of ICU-acquired infections. Patients presenting maximum daily CRP variation >4.1 mg/dl plus a CRP level >8.7 mg/dl had an 88% risk of infection.
Hyperbaric Oxygen Reduces Acetaminophen Toxicity and Increases HIF‐1α Expression
Authors: Salhanick Steven D. , Belikoff Bryan , Orlow Daniel , Holt Douglas , Reenstra Wende , Buras Jon A. 
Published: April 2006

Objectives:
To investigate the effect of hyperbaric oxygen (HBO2) on acetaminophen (APAP)‐induced hepatotoxicity. The authors further evaluated the effects of APAP poisoning and HBO2 on the expression and function of hypoxia‐inducible factor 1‐alpha (HIF‐1α) in an effort to further describe the mechanisms of APAP‐induced hepatotoxicity. In vitro assays were performed to better understand the effects of HBO2 on HIF‐1α function.
Methods:
In vivo, four groups of C57BL/6 mice were treated as follows: APAP only, APAP followed by HBO2, HBO2 only, and untreated shams. Plasma alanine aminotransferase activity was measured, and hepatic HIF‐1α induction was determined by Western blot. In vitro, cultured HEP G2 hepatocytes were exposed to HBO2, hypoxia (2.5% O2), or normoxia. HIF‐1α DNA‐binding and transcriptional activity were assessed.
Results:
Alanine aminotransferase activity was reduced in the APAP+HBO2 group (2,606 IU/L ± 4,080; vs. APAP: 6,743 ± 3,397, p = 0.01 at 6 hours). APAP‐only, HBO2‐only, and APAP+HBO2 treatments all increased HIF‐1α expression relative to shams (p = 0.02, p = 0.02, and p < 0.01, respectively). HBO2 increased HIF‐1α DNA binding 5.7 (± 1.2)‐fold relative to controls (p < 0.01); however, a parallel increase in HIF functional transcriptional activity did not occur.
Conclusions:
Hyperbaric oxygen reduced early APAP‐induced hepatocellular injury. APAP poisoning increases HIF‐1α protein levels and functional activity. HBO2 increases HIF‐1α protein levels and DNA binding without a corresponding increase in transcriptional activity.
Genetic Variation in the Visfatin Gene (PBEF1) and Its Relation to Glucose Metabolism and Fat-Depot-Specific Messenger Ribonucleic Acid Expression in Humans
Authors: Böttcher Yvonne , Teupser Daniel , Enigk Beate , Berndt Janin , Klöting Nora , Schön Michael R. , Thiery Joachim , Blüher Matthias , Stumvoll Michael , Kovacs Peter 
Published: April 2006

Abstract
Context and Objective: Visfatin is a peptide suggested to play a role in glucose homeostasis. In the present study, we investigated the role of genetic variation in the visfatin gene in the pathophysiology of obesity/type 2 diabetes mellitus (T2DM).
Design: The visfatin gene (PBEF1) was sequenced in DNA samples from 24 nonrelated Caucasian subjects. Identified genetic variants were used for association analyses of T2DM in a case-control study (503 diabetic subjects and 476 healthy controls) and T2DM-related traits in 626 nondiabetic subjects. The effect of genetic variation in the visfatin gene on its mRNA expression in a subgroup of 157 nondiabetic subjects with measurements of visfatin mRNA expression in visceral and sc fat depots was also analyzed.
Results: Seven single-nucleotide polymorphisms (SNPs) and one insertion/deletion were identified. Three SNPs (rs9770242, −948G→T, rs4730153) that were representatives of their linkage disequilibrium groups were genotyped in Caucasians from Germany with a wide range of body fat distribution and insulin sensitivity for association analyses. No association of T2DM with any of the genotyped SNPs or their haplotypes was found. However, the ratio of visceral/sc visfatin mRNA expression was associated with all three genetic polymorphisms (P &lt; 0.05). Moreover, the −948G→T variant was associated with 2-h plasma glucose and fasting insulin concentrations (P &lt; 0.05) in nondiabetic subjects.
Conclusions: In conclusion, our data suggest that genetic variation in the visfatin gene may have a minor effect on visceral and sc visfatin mRNA expression profiles but does not play a major role in the development of obesity or T2DM.
Electrolysis Using Composite Plated Electrodes. Preparation of a Binary Type Composite Plated Nickel Electrode with Poly(tetrafluoroethylene) and Silica Gel and Its Application in Electroreduction of Aldehydes
Authors: Ono Yasushi , Nishiki Yoshinori , Nonaka Tsutomu 
Published: April 2006

Abstract
A binary type composite plated nickel electrode with poly(tetrafluoroethylene) and silica gel as hydrophobic and hydrophilic components, respectively, was prepared and applied to electroreduction of aldehydes. The electrode gave higher current efficiencies for the reduction and higher selectivities for the corresponding alcohols than unplated and plated electrodes with either poly(tetrafluoroethylene) or silica gel.
Photolysis of Hydrophobic Vitamin B12 Derivatives Covalently Bound to Lipid in Aqueous Media
Authors: Murakami Yukito , Hisaeda Yoshio , Ogawa Akihiro , Ohno Teruhisa 
Published: April 2006

Abstract
An alkyl ligand coordinated to hydrophobic vitamin B12 derivatives covalently bound to N,N-dihexadecyl-Nα-[6-(trimethylammonio)hexanoyl]-l-aspartamide bromide underwent a novel bromination reaction along with its rearrangement in the single-walled vesicle of N,N-dihexadecyl-Nα-[6-(trimethylammonio)hexanoyl]-l-alaninamide bromide under photolysis conditions.