bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Rho-associated coiled-coil containing protein kinase enhances the activation of epidermal growth factor receptor in pancreatic cancer cells
Authors: Nakashima Masanori , Adachi Seiji , Yasuda Ichiro , Yamauchi Takahiro , Kawaguchi Junji , Hanamatsu Toshimasa , Yoshioka Takashi , Okano Yukio , Hirose Yoshinobu , Kozawa Osamu , Moriwaki Hisataka 
Published: July 2011

Abstract

Background
Rho-associated coiled-coil containing protein kinase (Rho-kinase/ROCK) is involved in various cellular functions including cell proliferation, and is generally considered to be oncogenic, while some studies show that ROCK functions as a negative regulator of cancer progression. As a result, the precise role of ROCK remains controversial. We have previously reported that Rho-kinase/ROCK negatively regulates epidermal growth factor (EGF)-induced cell proliferation in SW480 colon cancer cells. In the present study, we investigated the role of ROCK in EGF receptor (EGFR) signaling in the pancreatic cancer cell lines, Panc1, KP3 and AsPc1.

Results
In these cells, Y27632, a specific ROCK inhibitor, enhanced EGF-induced BrdU incorporation. The blockade of EGF stimulation utilizing anti-EGFR-neutralizing antibodies suppressed Panc1 cell proliferation. EGF induced RhoA activity, as well as the phosphorylation of cofilin and myosin light chain (MLC), both targets of ROCK signaling, and Y27632 suppressed both of these processes, indicating that the phosphorylation of cofilin and MLC by EGF occurs through ROCK in Panc1 cells. EGF-induced phosphorylation of EGFR at tyrosine residues was augmented when the cells were pretreated with Y27632 or were subjected to gene silencing using ROCK-siRNA. We also obtained similar results using transforming growth factor-α. In addition, EGF-induced phosphorylation of p44/p42 mitogen-activated protein kinase and Akt were also enhanced by Y27632 or ROCK-siRNA. Moreover, an immunofluorescence microscope study revealed that pretreatment with Y27632 delayed EGF-induced internalization of EGFR. Taken together, these data indicate that ROCK functions to switch off EGFR signaling by promoting the internalization of the EGFR.

Conclusions
While EGF first stimulates the activation of the EGFR and subsequently increases cancer cell proliferation, EGF concurrently induces the activation of ROCK, which then turns off the activated EGFR pathway via a negative feedback system.
Irinotecan induces steroid and xenobiotic receptor (SXR) signaling to detoxification pathway in colon cancer cells
Authors: Basseville Agnes , Preisser Laurence , de Carné Trécesson Sophie , Boisdron-Celle Michèle , Gamelin Erick , Coqueret Olivier , Morel Alain 
Published: July 2011

Abstract

Background
Resistance to chemotherapy remains one of the principle obstacles to the treatment of colon cancer. In order to identify the molecular mechanism of this resistance, we investigated the role of the steroid and xenobiotic receptor (SXR) in the induction of drug resistance. Indeed, this nuclear receptor plays an important role in response to xenobiotics through the upregulation of detoxification genes. Following drug treatments, SXR is activated and interacts with the retinoid X receptor (RXR) to induce expression of some genes involved in drug metabolism such as phase I enzyme (like CYP), phase II enzymes (like UGT) and transporters (e.g. MDR1).

Results
In this study, we have shown that endogenous SXR is activated in response to SN-38, the active metabolite of the anticancer drug irinotecan, in human colon cancer cell lines. We have found that endogenous SXR translocates into the nucleus and associates with RXR upon SN-38 treatment. Using ChIP, we have demonstrated that endogenous SXR, following its activation, binds to the native promoter of the CYP3A4 gene to induce its expression. RNA interference experiments confirmed SXR involvement in CYP3A4 overexpression and permitted us to identify CYP3A5 and MRP2 transporter as SXR target genes. As a consequence, cells overexpressing SXR were found to be less sensitive to irinotecan treatment.

Conclusions
Altogether, these results suggest that the SXR pathway is involved in colon cancer irinotecan resistance in colon cancer cell line via the upregulation of select detoxification genes.
Effects of simvastatin on apolipoprotein M in vivo and in vitro
Authors: Zhang Xiaoying , Mao Shubing , Luo Guanghua , Wei Jiang , Berggren-Söderlund Maria , Nilsson-Ehle Peter , Xu Ning 
Published: July 2011

Abstract

Objective
To investigate effects of lipid lowering drug, simvastatin, on apolipoprotein M expression in the hyperlipidemic mice and in hepatic cell line, HepG2 cells.

Methods
Swiss male mice were randomly divided into the high fat group and control group, and were intragastrically fed with 0.9% saline (control group) or lipid emulsion (high fat group) at the daily dosage of 15 ml/kg body weight, respectively. After 8 weeks feeding, the hyperlipidemic model was successfully induced and these hyperlipidemic mice were then randomly divided into three experimental groups: vehicle control group, high-dose simvastatin-treated group (100 mg/kg body weight), and low-dose simvastatin-treated group (10 mg/kg body weight). Mice were dosed daily for 6 weeks of simvastatin before mice were sacrificed for determining serum lipid profile and apoM protein levels that was determined by using dot blotting analysis. Effects of simvastatin on apoM mRNA expression in the HepG2 cells were determined by real-time RT-PCR.

Results
Comparing to high fat model mice without simvastatin treatment, 100 mg/kg simvastatin could significantly increase serum total cholesterol (P < 0.05). Serum apoM levels, in all mice, were significantly lower in the mice at the age of 26 weeks than the mice at 12 weeks old (P < 0.05), which indicated that serum apoM levels were significantly correlated to the mice age. It demonstrated also that treatment of simvastatin did not influence serum apoM levels in these mouse model, although serum apoM levels were increased by about 13% in the 10 mg/kg simvastatin group than in the vehicle control group without simvastatin. In HepG2 cell cultures, simvastatin could significantly decrease apoM mRNA levels with dose- and time-dependent manners. At 10 μM simvastatin treatment, apoM mRNA decreased by 52% compared to the controls.

Conclusion
The present study suggested that simvastatin, in vivo, had no effect on apoM levels in the hyperlipidemic mouse model. ApoM serum levels in mice were significantly correlated to the animal's age, whereas in cell cultures simvastatin does inhibit apoM expression in the HepG2 cells. The mechanism behind it is not known yet.
Human MMP28 expression is unresponsive to inflammatory stimuli and does not correlate to the grade of intervertebral disc degeneration
Authors: Klawitter Marina , Quero Lilian , Bertolo Alessando , Mehr Marco , Stoyanov Jivko , Nerlich Andreas G , Klasen Juergen , Aebli Nikolaus , Boos Norbert , Wuertz Karin 
Published: July 2011

Abstract

Background
MMP28 (epilysin) is a recently discovered member of the MMP (matrix metalloproteinase) family that is, amongst others, expressed in osteoarthritic cartilage and intervertebral disc (IVD) tissue. In this study the hypothesis that increased expression of MMP28 correlates with higher grades of degeneration and is stimulated by the presence of proinflammatory molecules was tested. Gene expression levels of MMP28 were investigated in traumatic and degenerative human IVD tissue and correlated to the type of disease and the degree of degeneration (Thompson grade). Quantification of MMP28 gene expression in human IVD tissue or in isolated cells after stimulation with the inflammatory mediators lipopolysaccharide (LPS), interleukin (IL)-1β, tumor necrosis factor (TNF)-α or the histondeacetylase inhibitor trichostatin A was performed by real-time RT PCR.

Results
While MMP28 expression was increased in individual cases with trauma or disc degeneration, there was no significant correlation between the grade of disease and MMP28 expression. Stimulation with LPS, IL-1β, TNF-α or trichostatin A did not alter MMP28 gene expression at any investigated time point or any concentration.

Conclusions
Our results demonstrate that gene expression of MMP28 in the IVD is not regulated by inflammatory mechanisms, is donor-dependent and cannot be positively or negatively linked to the grade of degeneration and only weakly to the occurrence of trauma. New hypotheses and future studies are needed to find the role of MMP28 in the intervertebral disc.
Multi-Segment Direct Inject nano-ESI-LTQ-FT-ICR-MS/MS For Protein Identification
Authors: Chen Jing , Canales Lorena , Neal Rachel E 
Published: July 2011

AbstractReversed phase high performance liquid chromatography (HPLC) interfaced to electrospray tandem mass spectrometry (MS/MS) is commonly used for the identification of peptides from proteolytically cleaved proteins embedded in a polyacrylamide gel matrix as well as for metabolomics screening. HPLC separations are time consuming (30-60 min average), costly (columns and mobile phase reagents), and carry the risk of column carry over between samples. The use of a chip-based nano-ESI platform (Advion NanoMate) based on replaceable nano-tips for sample introduction eliminates sample cross-contamination, provides unchanging sample matrix, and enhances spray stability with attendant increases in reproducibility. Recent papers have established direct infusion nano-ESI-MS/MS utilizing the NanoMate for protein identification of gel spots based on full range MS scans with data dependent MS/MS. In a full range scan, discontinuous ion suppression due to sample matrix can impair identification of putative mass features of interest in both the proteomic and metabolomic workflows. In the current study, an extension of an established direct inject nano-ESI-MS/MS method is described that utilizes the mass filtering capability of an ion-trap for ion packet separation into four narrow mass ranges (50 amu overlap) with segment specific dynamic data dependent peak inclusion for MS/MS fragmentation (total acquisition time of 3 minutes). Comparison of this method with a more traditional nanoLC-MS/MS based protocol utilizing solvent/sample stream splitting to achieve nanoflow demonstrated comparable results for protein identification from polyacrylamide gel matrices. The advantages of this method include full automation, lack of cross-contamination, low cost, and high throughput.
A proteomic analysis of Curcuma comosa Roxb. rhizomes
Authors: Boonmee Apaporn , Srisomsap Chantragan , Chokchaichamnankit Daranee , Karnchanatat Aphichart , Sangvanich Polkit 
Published: July 2011

Abstract

Background
The similarly in plant physiology and the difficulty of plant classification, in some medicinal plant species, especially plants of the Zingiberaceae family, are a major problem for pharmacologists, leading to mistaken use. To overcome this problem, the proteomic base method was used to study protein profiles of the plant model, Curcuma comosa Roxb., which is a member of the Zingiberaceae and has been used in traditional Thai medicine as an anti-inflammatory agent for the treatment of postpartum uterine bleeding.

Results
Due to the complexity of protein extraction from this plant, microscale solution-phase isoelectric focusing (MicroSol-IEF) was used to enrich and improve the separation of Curcuma comosa rhizomes phenol-soluble proteins, prior to resolving and analyzing by two-dimensional polyacrylamide gel electrophoresis and identification by tandem mass spectrometry. The protein patterns showed a high abundance of protein spots in the acidic range, including three lectin proteins. The metabolic and defense enzymes, such as superoxide dismutase (SOD) and ascorbate peroxidase, that are associated with antioxidant activity, were mainly found in the basic region. Furthermore, cysteine protease was found in this plant, as had been previously reported in other Zingiberaceae plants.

Conclusion
This report presents the protein profiles of the ginger plant, Curcuma comosa. Several interesting proteins were identified in this plant that may be used as a protein marker and aid in identifying plants of the Zingiberaceae family.
The impact of burning mouth syndrome on health-related quality of life
Authors: Souza Fabrício TA , Santos Tálita PM , Bernardes Vanessa F , Teixeira Antônio L , Kümmer Arthur M , Silva Tarcília A , Abreu Mauro HNG 
Published: July 2011

Abstract

Background
Burning mouth syndrome is a chronic disorder that is characterized by a burning sensation and a normal clinical appearance of the oral mucosa. This condition often affects the health-related quality of life in patients. As such, the aim of this study was to compare the health-related quality of life of patients with BMS and healthy controls, using the validated Portuguese versions of the SF-36 and OHIP-49 questionnaires.

Methods
A calculated sample of Brazilian patients with BMS (n = 26) was compared with a control group (n = 27), paired for gender and age. Sociodemographic information and clinical characteristics were obtained, and interviews were conducted using the SF-36 and OHIP-49. To evaluate the normality of the variables, we used the Kolmogorov-Smirnov test. The chi-square test, Fisher exact test and Mann-Whitney U-Test were used to compare sociodemographic and clinical characteristics of individuals with BMS and controls Mann-Whitney U-test were carried out to compare SF-36 and OHIP-49 between BMS patients and controls. The significance level was set at 0.05. To compare the dimensions of the SF-36 and OHIP-49 between BMS patients and controls, we considered Bonferroni correction. So for comparison of the dimensions, the significance level was set at 0.00625 for SF-36 and at 0.00714 for OHIP-49.

Results
The clinical and demographic data were similar in both groups (P > 0.05). SF-36 scores were significantly lower in all domains for patients with BMS (P < 0.00625). OHIP-49 scores were higher for individuals with BMS (P < 0.00714).

Conclusions
BMS has a negative impact on the health-related quality of life of individuals, as can be shown by instruments such as the SF-36 and OHIP-49. So, the evaluation of quality of life might be useful for more information about the nature and severity of BMS, to evaluate the effects of treatment protocols, in order to improve their outcomes by means a humanized clinical practice.
Expression, immunolocalization and processing of fertilins ADAM-1 and ADAM-2 in the boar (sus domesticus) spermatozoa during epididymal maturation
Authors: Fàbrega Anna , Guyonnet Benoît , Dacheux Jean-Louis , Gatti Jean-Luc , Puigmulé Marta , Bonet Sergi , Pinart Elisabeth 
Published: July 2011

Abstract
Fertilin alpha (ADAM-1) and beta (ADAM-2) are integral membrane proteins of the ADAM family that form a fertilin complex involved in key steps of the sperm-oocyte membrane interaction. In the present work, we analyzed the presence of ADAM-1 and ADAM-2 mRNAs, the spermatozoa proteins' processing and their sub-cellular localization in epididymal samples from adult boars. ADAM-1 and ADAM-2 mRNAs were highly produced in the testis, but also in the vas efferens and the epididymis. On immunoblots of sperm extracts, ADAM-1 subunit appeared as a main reactive band of ~50-55 kDa corresponding to occurrence of different isoforms throughout the epididymal duct, especially in the corpus region where isoforms ranged from acidic to basic pI. In contrast, ADAM-2 was detected as several bands of ~90 kDa, ~75 kDa, ~50-55 kDa and ~40 kDa. The intensity of high molecular mass bands decreased progressively in the distal corpus where lower bands were also transiently observed, and only the ~40 kDa was observed in the cauda. The presence of bands of different molecular weights likely results from a proteolytic processing occurring mainly in the testis for ADAM-1, and also throughout the caput epididymis for ADAM-2. Immunolocalization showed that fertilin migrates from the acrosomal region to the acrosomal ridge during the sperm transit from the distal corpus to the proximal cauda. This migration is accompanied by an important change in the extractability of a part of ADAM-1 from the sperm membrane. This suggests that the fertilin surface migration may be triggered by the biochemical changes induced by the epididymal post-translational processing of both ADAM1 and ADAM-2. Different patterns of fertilin immunolocalization then define several populations of spermatozoa in the cauda epididymis. Characterization of such fertilin complex maturation patterns is an important step to develop fertility markers based on epididymal maturation of surface membrane proteins in domestic mammals.
Spectratyping analysis of the islet-reactive T cell repertoire in diabetic NOD Igμnull mice after polyclonal B cell reconstitution
Authors: Vong Allen M , Daneshjou Nazila , Norori Patricia Y , Sheng Huiming , Braciak Todd A , Sercarz Eli E , Gabaglia Claudia Raja 
Published: July 2011

AbstractBackgroundNon Obese Diabetic mice lacking B cells (NOD.Igμnullmice) do not develop diabetes despite their susceptible background. Upon reconstitution of B cells using a chimera approach, animals start developing diabetes at 20 weeks of age.MethodsWe have used the spectratyping technique to follow the T cell receptor (TCR) V beta repertoire of NOD.Igμnullmice following B cell reconstitution. This technique provides an unbiased approach to understand the kinetics of TCR expansion. We have also analyzed the TCR repertoire of reconstituted animals receiving cyclophosphamide treatment and following tissue transplants to identify common aggressive clonotypes.ResultsWe found that B cell reconstitution of NOD.Igμnullmice induces a polyclonal TCR repertoire in the pancreas 10 weeks later, gradually diversifying to encompass most BV families. Interestingly, these clonotypic BV expansions are mainly confined to the pancreas and are absent from pancreatic lymph nodes or spleens. Cyclophosphamide-induced diabetes at 10 weeks post-B cell reconstitution reorganized the predominant TCR repertoires by removing potential regulatory clonotypes (BV1, BV8 and BV11) and increasing the frequency of others (BV4, BV5S2, BV9, BV16-20). These same clonotypes are more frequently present in neonatal pancreatic transplants under the kidney capsule of B-cell reconstituted diabetic NOD.Igμnullmice, suggesting their higher invasiveness. Phenotypic analysis of the pancreas-infiltrating lymphocytes during diabetes onset in B cell reconstituted animals show a predominance of CD19+B cells with a B:T lymphocyte ratio of 4:1. In contrast, in other lymphoid organs (pancreatic lymph nodes and spleens) analyzed by FACS, the B:T ratio was 1:1. Lymphocytes infiltrating the pancreas secrete large amounts of IL-6 and are of Th1 phenotype after CD3-CD28 stimulationin vitro.ConclusionsDiabetes in NOD.Igμnullmice appears to be caused by a polyclonal repertoire of T cell accumulation in pancreas without much lymphoid organ involvement and is dependent on the help by B cells.
Membranous expression of Her3 is associated with a decreased survival in head and neck squamous cell carcinoma
Authors: Takikita Mikiko , Xie Ran , Chung Joon-Yong , Cho Hanbyoul , Ylaya Kris , Hong Seung-Mo , Moskaluk Christopher A , Hewitt Stephen M 
Published: July 2011

Abstract

Background
Head and neck squamous cell carcinoma (HNSCC) still remains a lethal malignancy benefiting from the identification of the new target for early detection and/or development of new therapeutic regimens based on a better understanding of the biological mechanism for treatment. The overexpression of Her2 and Her3 receptors have been identified in various solid tumors, but its prognostic relevance in HNSCC remains controversial.

Methods
Three hundred eighty-seven primary HNSCCs, 20 matching metasis and 17 recurrent HNSCCs were arrayed into tissue microarrays. The relationships between Her2 and Her3 protein expression and clinicopathological parameters/survival of HNSCC patients were analyzed with immunohistochemistry.

Results
Her3 is detected as either a cytoplasmic or a membranous dominant expression pattern whereas Her2 expression showed uniform membranous form. In primary tumor tissues, high membranous Her2 expression level was found in 104 (26.9%) cases while positive membranous and cytoplasmic Her3 expression was observed in 34 (8.8%) and 300 (77.5%) samples, respectively. Membranous Her2 expression was significantly associated with histological grade (P = 0.021), as grade 2 tumors showed the highest positive expression. Membranous Her3 over-expression was significantly prevalent in metastatic tissues compared to primary tumors (P = 0.003). Survival analysis indicates that membranous Her3 expression is significantly associated with worse overall survival (P = 0.027) and is an independent prognostic factor in multivariate analysis (hazard ratio, 1.51; 95% confidence interval, 1.01-2.23; P = 0.040).

Conclusions
These results suggest that membranous Her3 expression is strongly associated with poor prognosis of patients with HNSCC and is a potential candidate molecule for targeted therapy.
Brain cavernomas associated with en coup de sabre linear scleroderma: Two case reports
Authors: Fain Emily T , Mannion Melissa , Pope Elena , Young Daniel W , Laxer Ronald M , Cron Randy Q 
Published: July 2011

Abstract
Linear scleroderma is a form of localized scleroderma that primarily affects the pediatric population. When it occurs on the scalp or forehead, it is termed "en coup de sabre". In the en coup de sabre subtype, many extracutaneous associations, mostly neurological, have been described. A patient with linear scleroderma en coup de sabre was noted to have ipsilateral brain cavernomas by magnetic resonance imaging. Using a worldwide pediatric rheumatology electronic list-serve, another patient with the same 2 conditions was identified. These two patients are reported in this study. Consideration of neuroimaging studies to disclose abnormal findings in patients with linear scleroderma en coup de sabre is important for potentially preventing and treating neurological manifestations associated with this condition.
Atom devices based on single dopants in silicon nanostructures
Authors: Moraru Daniel , Udhiarto Arief , Anwar Miftahul , Nowak Roland , Jablonski Ryszard , Hamid Earfan , Tarido Juli Cha , Mizuno Takeshi , Tabe Michiharu 
Published: July 2011

Abstract
Silicon field-effect transistors have now reached gate lengths of only a few tens of nanometers, containing a countable number of dopants in the channel. Such technological trend brought us to a research stage on devices working with one or a few dopant atoms. In this work, we review our most recent studies on key atom devices with fundamental structures of silicon-on-insulator MOSFETs, such as single-dopant transistors, preliminary memory devices, single-electron turnstile devices and photonic devices, in which electron tunneling mediated by single dopant atoms is the essential transport mechanism. Furthermore, observation of individual dopant potential in the channel by Kelvin probe force microscopy is also presented. These results may pave the way for the development of a new device technology, i.e., single-dopant atom electronics.