bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involvement of the epidermal growth factor receptor in the modulation of multidrug resistance in human hepatocellular carcinoma cells in vitro
Authors: Hoffmann Katrin , Xiao Zhi , Franz Clemens , Mohr Elvira , Serba Susanne , Büchler Markus W , Schemmer Peter 
Published: December 2011

Abstract

Background
Hepatocellular carcinoma (HCC) is a molecular complex tumor with high intrinsic drug resistance. Recent evidence suggests an involvement of the tyrosine kinase pathway in the regulation of ATP-binding cassette protein (ABC-transport protein) mediated multidrug resistance in cancer cells. The aim of this study was to examine whether EGFR inhibition sensitizes HCCs to chemotherapy and to elucidate its mechanism.

Results
Chemotherapeutic treatment induces multidrug resistance and significantly increases ABC-transport protein expression and function in a time- and dose-dependent manner in HCC cells. Furthermore, cytostatic treatment increases the mRNA expression of tyrosine kinases and induces the phosphorylation of ERK. EGF activation of the tyrosine kinase pathway up-regulated the ABC-transport protein mRNA expression and enhanced the survival of resistant HCC cells. Consistent with these effects, inhibition of the EGFR using siRNA decreased the ABC-transport protein mRNA expression and inhibited the proliferation of resistant cells. Additional treatment with Gefitinib, a clinically approved EGFR inhibitor, caused a dose-dependent reversal of resistance to conventional chemotherapy.

Conclusion
The present study demonstrates that the multidrug resistance of HCC is modulated through the EGF-activated tyrosine kinase cascade. Consequentially, the restoration of chemosensitivity by EGFR inhibition may lead towards new tailored therapies in patients with highly resistant tumors.
Tetradecylthioacetic acid inhibits proliferation of human SW620 colon cancer cells - gene expression profiling implies endoplasmic reticulum stress
Authors: Lundemo Anne G , Pettersen Caroline HH , Berge Kjetil , Berge Rolf K , Schønberg Svanhild A 
Published: December 2011

Abstract

Background
Previous reports have shown an antiproliferative effect of the synthetic, 3-thia fatty acid tetradecylthioacetic acid (TTA) on different cancer cells in vitro and in vivo. The mechanisms behind the observed effects are poorly understood. We therefore wanted to explore the molecular mechanisms involved in TTA-induced growth inhibition of the human colon cancer cell line SW620 by gene expression profiling.

Methods
An antiproliferative effect of TTA on SW620 cells in vitro was displayed in real time using the xCELLigence System (Roche). Affymetrix gene expression profiling was performed to elucidate the molecular mechanisms behind the antiproliferative effect of TTA. Changes in gene expression were verified at protein level by western blotting.

Results
TTA reduced SW620 cell growth, measured as baseline cell index, by 35% and 55% after 48 h and 72 h, respectively. We show for the first time that TTA induces an endoplasmic reticulum (ER) stress response in cancer cells. Gene expression analysis revealed changes related to ER stress and unfolded protein response (UPR). This was verified at protein level by phosphorylation of eukaryote translation initiation factor 2 alpha (eIF2α) and downstream up-regulation of activating transcription factor 4 (ATF4). Transcripts for positive and negative cell cycle regulators were down- and up-regulated, respectively. This, together with a down-regulation of Cyclin D1 at protein level, indicates inhibition of cell cycle progression. TTA also affected transcripts involved in calcium homeostasis. Moreover, mRNA and protein level of the ER stress inducible C/EBP-homologous protein (CHOP), Tribbles homolog 3 (Drosophila) (TRIB3) and CCAAT/enhancer binding protein beta (C/EBPβ) were enhanced, and the C/EBPβ LIP/LAP ratio was significantly increased. These results indicate prolonged ER stress and a possible link to induction of cell death.

Conclusion
We find that TTA-induced growth inhibition of SW620 cells seems to be mediated through induction of ER stress and activation of the UPR pathway.
Microvessel density and heparanase over-expression in clear cell renal cell cancer: correlations and prognostic significances
Authors: Ren Juchao , Liu Hainan , Yan Lei , Tian Sujian , Li Dawei , Xu Zhonghua 
Published: December 2011

Abstract

Background
Tumor angiogenesis is important in the progression of malignancies, and heparanase plays an important role in sustaining the pathology of clear cell renal cell cancer (ccRCC). The study was carried out to investigate the correlations between microvessel density (MVD) and heparanase expression containing prognostic significances in the patients with ccRCC.

Methods
Specimens from 128 patients with ccRCC were investigated by immunohistochemistry for MVD. RT-PCR and immunohistochemistry were used to detect heparanase expression. Correlations between MVD, heparanase expression, and various clinico-pathological factors were studied. The prognostic significances of MVD and heparanase expression were also analysed.

Results
We discovered a statistically significant prevalence of higher MVD in ccRCC compared with adjacent normal renal tissues. MVD was positively correlated with TNM stage and distant metastasis in ccRCC patients, and was also correlated with the expression level of heparanase.
Heparanase is over-expressed and correlated with TNM stage, histologic grade, distant metastasis and lymphatic metastasis in ccRCC. High MVD and heparanase over-expression inversely correlate with the survival of ccRCC patients.

Conclusions
Heparanase contributes to angiogenesis of ccRCC and over-expression of heparanase is an independent predictors of prognosis for ccRCC. MVD is correlated with tumor development and metastasis in ccRCC.
IVF/ICSI outcomes after culture of human embryos at low oxygen tension: a meta-analysis
Authors: Gomes Sobrinho David B , Oliveira Joao Batista A , Petersen Claudia G , Mauri Ana L , Silva Liliane FI , Massaro Fabiana C , Baruffi Ricardo LR , Cavagna Mario , Franco José G 
Published: December 2011

Abstract

Background
Improved pregnancy, implantation, and birth rates have been reported after the use of reduced O2 concentration during embryo culture, mainly due to a reduction of the cumulative detrimental effects of reactive oxygen species. However, some studies have failed to report any positive effects. The objective of this meta-analysis was to evaluate the effect of a low-O2 environment on IVF/intracytoplasmic sperm injection (ICSI) outcomes.

Methods
All available published and ongoing randomised trials that compared the effects of low (~5%; OC~5) and atmospheric (~20%; OC~20) oxygen concentrations on IVF/ICSI outcomes were included. Search strategies included online surveys of databases from 1980 to 2011. The outcomes measured were fertilisation rate, implantation rate and ongoing pregnancy rates. The fixed effects model was used to calculate the odds ratio.

Results
Seven studies were included in this analysis. The pooled fertilisation rate did not differ significantly (P = 0.54) between the group of oocytes cultured at low O2 tension and the group at atmospheric O2 tension. Concerning all cycles, the implantation (P = 0.06) and ongoing pregnancy (P = 0.051) rates were not significantly different between the group receiving transferred sets containing only OC~5 embryos and the group receiving transferred sets with only OC~20 embryos. In a meta-analysis performed for only those trials in which embryos were transferred on day 2/3, implantation (P = 0.63) and ongoing pregnancy (P = 0.19) rates were not significantly different between the groups. In contrast, when a meta-analysis was performed using only trials in which embryos were transferred on days 5 and 6 (at the blastocyst stage), the group with transferred sets of only OC~5 embryos showed a statistically significantly higher implantation rate (P = 0.006) than the group receiving transferred sets with only OC~20 embryos, although the ongoing pregnancy (P = 0.19) rates were not significantly different between the groups.

Conclusions
Despite some promising results, it seems too early to conclude that low O2 culture has an effect on IVF outcome. Additional randomised controlled trials are necessary before evidence-based recommendations can be provided. It should be emphasised that the present meta-analysis does not provide any evidence that low oxygen concentration is unnecessary.
Huh-7 cell line as an alternative cultural model for the production of human like erythropoietin (EPO)
Authors: Kausar Humera , Gull Sana , Ijaz Bushra , Ahmad Waqar , Sarwar Muhammad Tahir , Iqbal Zafar , Nawaz Zafar , Riazuddin Sheikh , Hassan Sajida 
Published: December 2011

Abstract

Background and Aims
Erythropoietin (EPO) is a glycoprotein hormone which is required to regulate the production of red blood cells. Deficiency of EPO is known to cause anemia in chronically infected renal patients and they require regular blood transfusion. Availability of recombinant EPO has eliminated the need for blood transfusion and now it is extensively used for the treatment of anemia. Glycosylation of erythropoietin is essential for its secretion, stability, protein conformation and biological activity. However, maintenance of human like glycosylation pattern during manufacturing of EPO is a major challenge in biotechnology. Currently, Chinese hamster ovary (CHO) cell line is used for the commercial production of erythropoietin but this cell line does not maintain glycosylation resembling human system. With the trend to eliminate non-human constituent from biopharmaceutical products, as a preliminary approach, we have investigated the potential of human hepatoma cell line (Huh-7) to produce recombinant EPO.

Materials and methods
Initially, the secretory signal and Kozak sequences was added before the EPO mature protein sequence using overlap extension PCR technique. PCR-amplified cDNA fragments of EPO was inserted into mammalian expression vector under the control of the cytomegalovirus (CMV) promoter and transiently expressed in CHO and Huh-7 cell lines. After RT-PCR analysis, ELISA and Western blotting was performed to verify the immunochemical properties of secreted EPO.

Results
Addition of secretory signal and Kozak sequence facilitated the extra-cellular secretion and enhanced the expression of EPO protein. Significant expression (P < 0.05) of EPO was observed in the medium from Huh-7 cell line.

Conclusion
Huh-7 cell line has a great potential to produce glycosylated EPO, suggesting the use of this cell line to produce glycoproteins of the therapeutic importance resembling to the natural human system.
Thermal conductivity of carbon nanotubes and graphene in epoxy nanofluids and nanocomposites
Authors: Martin-Gallego Mario , Verdejo Raquel , Khayet Mohamed , de Zarate Jose Maria Ortiz , Essalhi Mohamed , Lopez-Manchado Miguel Angel 
Published: December 2011

AbstractWe employed an easy and direct method to measure the thermal conductivity of epoxy in the liquid (nanofluid) and solid (nanocomposite) states using both rodlike and platelet-like carbon-based nanostructures. Comparing the experimental results with the theoretical model, an anomalous enhancement was obtained with multiwall carbon nanotubes, probably due to their layered structure and lowest surface resistance. Puzzling results for functionalized graphene sheet nanocomposites suggest that phonon coupling of the vibrational modes of the graphene and of the polymeric matrix plays a dominant role on the thermal conductivities of the liquid and solid states.PACS: 74.25.fc; 81.05.Qk; 81.07.Pr.
Improving the emission efficiency of MBE-grown GaN/AlN QDs by strain control
Authors: Niu Lang , Hao Zhibiao , Hu Jiannan , Hu Yibin , Wang Lai , Luo Yi 
Published: December 2011

Abstract
The quantum-confined stark effect induced by polarization has significant effects on the optical properties of nitride heterostructures. In order to improve the emission efficiency of GaN/AlN quantum dots [QDs], a novel epitaxial structure is proposed: a partially relaxed GaN layer followed by an AlN spacer layer is inserted before the growth of GaN QDs. GaN/AlN QD samples with the proposed structure are grown by molecular beam epitaxy. The results show that by choosing a proper AlN spacer thickness to control the strain in GaN QDs, the internal quantum efficiencies have been improved from 30.7% to 66.5% and from 5.8% to 13.5% for QDs emitting violet and green lights, respectively.
A fixed point approach to the hyers-ulam stability of a functional equation in various normed spaces
Authors: Kenary Hassan Azadi , Jang Sun Young , Park Choonkil 
Published: December 2011

AbstractUsing direct method, Kenary (Acta Universitatis Apulensis, to appear) proved the Hyers-Ulam stability of the following functional equation

f

(

m
x
+
n
y

)

=

(

m
+
n

)

f

(

x
+
y

)

2

+

(

m
-
n

)

f

(

x
-
y

)

2

in non-Archimedean normed spaces and in random normed spaces, where m, n are different integers greater than 1. In this article, using fixed point method, we prove the Hyers-Ulam stability of the above functional equation in various normed spaces.2010 Mathematics Subject Classification: 39B52; 47H10; 47S40; 46S40; 30G06; 26E30; 46S10; 37H10; 47H40.
Common fixed point results for three maps in generalized metric space
Authors: Abbas Mujahid , Nazir Talat , Saadati Reza 
Published: December 2011

Abstract
Mustafa and Sims [Fixed Point Theory Appl. 2009, Article ID 917175, 10, (2009)] generalized a concept of a metric space and proved fixed point theorems for mappings satisfying different contractive conditions. In this article, we extend and generalize the results obtained by Mustafa and Sims and prove common fixed point theorems for three maps in these spaces. It is worth mentioning that our results do not rely on continuity and commutativity of any mappings involved therein. We also introduce the notation of a generalized probabilistic metric space and obtain common fixed point theorem in the frame work of such spaces.

2000 Mathematics Subject Classification: 47H10.
Pathogenesis and phylogenetic analyses of canine distemper virus strain ZJ7 isolate from domestic dogs in China
Authors: Tan Bin , Wen Yong-Jun , Wang Feng-Xue , Zhang Shu-Qin , Wang Xiu-Dong , Hu Jia-Xin , Shi Xin-Chuan , Yang Bo-Chao , Chen Li-Zhi , Cheng Shi-Peng , Wu Hua 
Published: December 2011

Abstract
A new isolate of canine distemper virus (CDV), named ZJ7, was isolated from lung tissues of a dog suspected with CDV infection using MDCK cells. The ZJ7 isolate induced cytopathogenic effects of syncytia in MDCK cell after six passages. In order to evaluate pathogenesis of ZJ7 strain, three CDV sero-negative dogs were intranasally inoculated with its virus suspension. All infected dogs developed clinical signs of severe bloody diarrhea, conjunctivitis, ocular discharge, nasal discharge and coughing, fever and weight loss at 21 dpi, whereas the mock group infected with DMEM were normal. The results demonstrated that CDV-ZJ7 strain isolated by MDCK cell was virulent, and the nucleotide and amino acid sequences of strain ZJ7 had no change after isolation by MDCK cell when compared with the original virus from the fresh tissues. Molecular and phylogenetic analyses for the nucleocapsid (N), phosphoprotein (P) and receptor binding haemagglutinin (H) gene of the ZJ7 isolate clearly showed it is joins to the Asia 1 group cluster of CDV strains, the predominant genotype in China.
Intra- and Interfamily Phenotypic Diversity in Pain Syndromes Associated with a Gain-of-Function Variant of NaV1.7
Authors: Estación Mark , Han Chongyang , Choi Jin-Sung , Hoeijmakers Janneke GJ , Lauria Giuseppe , Drenth Joost PH , Gerrits Monique M , Dib-Hajj Sulayman D , Faber Catharina G , Merkies Ingemar SJ , Waxman Stephen G 
Published: December 2011

Background: Sodium channel NaV1.7 is preferentially expressed within dorsal root ganglia (DRG), trigeminal ganglia and sympathetic ganglion neurons and their fine-diamter axons, where it acts as a threshold channel, amplifying stimuli such as generator potentials in nociceptors. Gain-of-function mutations and variants (single amino acid substitutions) of NaV1.7 have been linked to three pain syndromes: Inherited Erythromelalgia (IEM), Paroxysmal Extreme Pain Disorder (PEPD), and Small Fiber Neuropathy (SFN). IEM is characterized clinically by burning pain and redness that is usually focused on the distal extremities, precipitated by mild warmth and relieved by cooling, and is caused by mutations that hyperpolarize activation, slow deactivation, and enhance the channel ramp response. PEPD is characterized by perirectal, periocular or perimandibular pain, often triggered by defecation or lower body stimulation, and is caused by mutations that severely impair fast-inactivation. SFN presents a clinical picture dominated by neuropathic pain and autonomic symptoms; gain-of-function variants have been reported to be present in approximately 30% of patients with biopsy-confirmed idiopathic SFN, and functional testing has shown altered fast-inactivation, slow-inactivation or resurgent current. In this paper we describe three patients who house the NaV1.7/I228M variant. Methods: We have used clinical assessment of patients, quantitative sensory testing and skin biopsy to study these patients, including two siblings in one family, in whom genomic screening demonstrated the I228M NaV1.7 variant. Electrophysiology (voltage-clamp and current-clamp) was used to test functional effects of the variant channel. Results: We report three different clinical presentations of the I228M NaV1.7 variant: presentation with severe facial pain, presentation with distal (feet, hands) pain, and presentation with scalp discomfort in three patients housing this NaV1.7 variant, two of which are from a single family. We also demonstrate that the NaV1.7/I228M variant impairs slow-inactivation, and produces hyperexcitability in both trigeminal ganglion and DRG neurons. Conclusion: Our results demonstrate intra- and interfamily phenotypic diversity in pain syndromes produced by a gain-of-function variant of NaV1.7.
Transcription factor binding sites are highly enriched within microRNA precursor sequences
Authors: Piriyapongsa Jittima , Jordan I King , Conley Andrew B , Ronan Tom , Smalheiser Neil R 
Published: December 2011

Abstract

Background
Transcription factors are thought to regulate the transcription of microRNA genes in a manner similar to that of protein-coding genes; that is, by binding to conventional transcription factor binding site DNA sequences located in or near promoter regions that lie upstream of the microRNA genes. However, in the course of analyzing the genomics of human microRNA genes, we noticed that annotated transcription factor binding sites commonly lie within 70- to 110-nt long microRNA small hairpin precursor sequences.

Results
We report that about 45% of all human small hairpin microRNA (pre-miR) sequences contain at least one predicted transcription factor binding site motif that is conserved across human, mouse and rat, and this rises to over 75% if one excludes primate-specific pre-miRs. The association is robust and has extremely strong statistical significance; it affects both intergenic and intronic pre-miRs and both isolated and clustered microRNA genes. We also confirmed and extended this finding using a separate analysis that examined all human pre-miR sequences regardless of conservation across species.

Conclusions
The transcription factor binding sites localized within small hairpin microRNA precursor sequences may possibly regulate their transcription. Transcription factors may also possibly bind directly to nascent primary microRNA gene transcripts or small hairpin microRNA precursors and regulate their processing.

Reviewers
This article was reviewed by Guillaume Bourque (nominated by Jerzy Jurka), Dmitri Pervouchine (nominated by Mikhail Gelfand), and Yuriy Gusev.
PathCase-SB architecture and database design
Authors: Cakmak Ali , Qi Xinjian , Coskun Sarp A , Das Mitali , Cheng En , Cicek A Ercument , Lai Nicola , Ozsoyoglu Gultekin , Ozsoyoglu Z Meral 
Published: December 2011

Abstract

Background
Integration of metabolic pathways resources and regulatory metabolic network models, and deploying new tools on the integrated platform can help perform more effective and more efficient systems biology research on understanding the regulation in metabolic networks. Therefore, the tasks of (a) integrating under a single database environment regulatory metabolic networks and existing models, and (b) building tools to help with modeling and analysis are desirable and intellectually challenging computational tasks.

Description
PathCase Systems Biology (PathCase-SB) is built and released. The PathCase-SB database provides data and API for multiple user interfaces and software tools. The current PathCase-SB system provides a database-enabled framework and web-based computational tools towards facilitating the development of kinetic models for biological systems. PathCase-SB aims to integrate data of selected biological data sources on the web (currently, BioModels database and KEGG), and to provide more powerful and/or new capabilities via the new web-based integrative framework. This paper describes architecture and database design issues encountered in PathCase-SB's design and implementation, and presents the current design of PathCase-SB's architecture and database.

Conclusions
PathCase-SB architecture and database provide a highly extensible and scalable environment with easy and fast (real-time) access to the data in the database. PathCase-SB itself is already being used by researchers across the world.
miR-15a and miR-16-1 inhibit the proliferation of leukemic cells by down-regulating WT1 protein level
Authors: Gao Shen-meng , Xing Chong-yun , Chen Chi-qi , Lin Si-si , Dong Pei-hong , Yu Fu-jun 
Published: December 2011

Abstract

Background
miR-15a and miR-16-1(miR-15a/16-1) have been implicated as tumor suppressors in chronic lymphocytic leukemia, multiple myeloma, and acute myeloid leukemic cells. However the mechanism of inhibiting the proliferation of leukemic cells is poorly understood.

Methods
K562 and HL-60 cells were transfected with pRS-15/16 or pRS-E, cell growth were measured by CCK-8 assay and direct cell count. Meanwhile WT1 protein and mRNA level were measured by Western blotting and quantitative real-time PCR.

Results
In this study we found that over-expression of miR-15a/16-1 significantly inhibited K562 and HL-60 cells proliferation. Enforced expression of miR-15a/16-1 in K562 and HL-60 cells significantly reduced the protein level of WT1 but not affected the mRNA level. However enforced expression of miR-15a/16-1 can not reduce the activity of a luciferase reporter carrying the 3'-untranslated region(3'UTR) of WT1. Silencing of WT1 by specific siRNA suppressed leukemic cells proliferation resembling that of miR-15a/16-1 over-expression. Anti-miR-15a/16-1 oligonucleotides (AMO) reversed the expression of WT1 in K562 and HL-60 cells. Finally, we found a significant inverse correlation between miR-15a or miR-16-1 expression and WT1 protein levels in primary acute myeloid leukemia (AML) blasts and normal controls.

Conclusions
These data suggest that miR-15a/16-1 may function as a tumor suppressor to regulate leukemic cell proliferation potentially by down-regulating the WT1 oncogene. However WT1 is not directly targeted by miR-15a/16-1 through miRNA-mRNA base pairing, therefore more study are required to understand the mechanism by which miR-15a/16-1 downregulate WT1.