bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sphingosine kinase 2 deficient tumor xenografts show impaired growth and fail to polarize macrophages towards an anti‐inflammatory phenotype
Authors: Weigert Andreas , Schiffmann Susanne , Sekar Divya , Ley Stephanie , Menrad Heidi , Werno Christian , Grosch Sabine , Geisslinger Gerd , Brüne Bernhard 
Published: May 2009

AbstractA challenging task of the immune system is to fight cancer cells. However, a variety of human cancers educate immune cells to become tumor supportive. This is exemplified for tumor‐associated macrophages (TAMs), which are polarized towards an anti‐inflammatory and cancer promoting phenotype. Mechanistic explanations, how cancer cells influence the macrophage phenotype are urgently needed to address potential anti‐cancer strategies along this line. One potential immune modulating compound, sphingosine‐1‐phosphate (S1P), was recently highlighted in both tumor growth and immune modulation. Using a xenograft model in nude mice, we demonstrate a supportive role of sphingosine kinase 2 (SphK2), one of the S1P‐producing enzymes for tumor progression. The growth of SphK2‐deficient MCF‐7 breast tumor xenografts was markedly delayed when compared with controls. Infiltration of macrophages in SphK2‐deficient and control tumors was comparable. However, TAMs from SphK2‐deficient tumors displayed a pronounced anti‐tumor phenotype, showing an increased expression of pro‐inflammatory markers/mediators such as NO, TNF‐α, IL‐12 and MHCII and a low expression of anti‐inflammatory IL‐10 and CD206. These data suggest a role for S1P, generated by SphK2, in early tumor development by affecting macrophage polarization. © 2009 UICC
Insulin‐like growth factor 1 receptor expression in wild‐type GISTs: A potential novel therapeutic target
Authors: Pantaleo Maria A. , Astolfi Annalisa , Di Battista Monica , Heinrich Michael C. , Paterini Paola , Scotlandi Katia , Santini Donatella , Catena Fausto , Manara Maria C. , Nannini Margherita , Maleddu Alessandra , Saponara Maristella , Lolli Cristian , Formica Serena , Biasco Guido 
Published: May 2009

AbstractAberrations of the Insulin‐like Growth Factor (IGF) system have been found in association with a variety of cancer types. The potential role of IGF1R has been postulated in a small subset of GISTs, but until now the implications of its aberrations have not been defined. The aim of the study was to examine the IGF1R status in patients with gastric GIST in regard to KIT and PDGFRA genotype. Fresh resection specimens were collected from 8 primary tumours [2 wild‐type (WT) and 6 mutant cases]. IGF1R was studied as gene expression profiling with Affymetrix GeneChip HG‐U133Plus 2.0 arrays and as genomic copy number with SNP array analysis Affymetrix Genome Wide Human SNP 6.0 arrays, and at protein level with western blotting (WB) and immunohistochemistry (IHC). The unsupervised analysis of gene expression profiling of our patients merged with a data set from gastric GISTs identified 2 patients out of 8 with different expression of IGF1R. The data were confirmed by WB and IHC. In particular, IGF1R was upregulated in 2 young patients (<30‐years old), who had both WT disease and metastases at diagnosis. The SNP array analysis showed that none of the tumours had IGF1R amplification. GISTs are characterized by abnormalities of the KIT and PDGFRA receptors that affect prognosis and response to tyrosine kinase inhibitors. Both young adult with WT GIST had the over‐expression of IGF1R at mRNA and protein level. These results further confirm the hypothesis that IGF1R may be a potential therapeutic target in GISTs lacking KIT and PDGFRA mutations. © 2009 UICC
No mutations of FGFR3 in normal urothelium in the vicinity of urothelial carcinoma of the bladder harbouring activating FGFR3 mutations in patients with bladder cancer
Authors: Otto Wolfgang , Denzinger Stefan , Bertz Simone , Gaumann Andreas , Wild Peter J. , Hartmann Arndt , Stoehr Robert 
Published: May 2009

AbstractMutations in the fibroblast growth factor receptor 3 (FGFR3) gene causing constitutive oncogenic protein activation have been shown to be frequent in papillary noninvasive bladder tumours and are associated with a low risk of progression and a favourable outcome. FGFR3 alterations have also been found in benign urothelial papilloma and flat urothelial hyperplasia suggesting FGFR3 alterations as an early event in bladder tumorigenesis. To date there is no data available on FGFR3 mutations in normal urothelium from patients with bladder cancer. We therefore analysed 64 samples of histopathological unsuspicious normal urothelium from 38 patients with FGFR3 mutated bladder tumours and 15 samples of urothelium from patients (n = 15) without any urothelial malignancy as a control group. Urothelial cells were microdissected from formalin‐fixed, paraffin‐embedded material. After DNA isolation whole genome amplification was done by I‐PEP‐PCR. FGFR3 mutations were detected using SNaPshot analysis. All samples could successfully be investigated. FGFR3 analyses did not reveal any mutation in the urothelium from neither the control group nor the bladder cancer group. All urothelial samples showed a wildtype sequence for FGFR3. These data suggest that mutations in the FGFR3 gene are not the earliest genetic alterations in bladder carcinogenesis and are associated with a hyperproliferative (hyperplastic) phenotype in the urothelium. Chromosomal alterations like deletions on chromosome 9q or aberrant promoter hypermethylation could play more important roles in early urothelial transformation than mutational FGFR3 activation. © 2009 UICC
Elevated level of 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine in leukocytes of BRCA1 mutation carriers compared to healthy controls
Authors: Dziaman Tomasz , Huzarski Tomasz , Gackowski Daniel , Rozalski Rafal , Siomek Agnieszka , Szpila Anna , Guz Jolanta , Lubinski Jan , Olinski Ryszard 
Published: May 2009

AbstractCarriers of BRCA1 mutation face highly increased risk of breast and ovarian cancer and some studies with cell culture suggest that the encoded protein may be involved in oxidatively damaged DNA repair. However, no studies concerning a possible link between oxidatively damaged DNA and BRCA1 deficiency have been conducted with the mutations carriers. Therefore, to assess an involvement of BRCA in oxidative damage to DNA in the present study a broad spectrum of parameters reflecting oxidative stress/DNA damage were analyzed in 3 subject groups; (i) carriers of BRCA1 mutations without symptoms of the disease; (ii) patients with breast or ovarian cancer with the mutations and (iii) the group of healthy subjects recruited from among close relatives of the group of carriers without symptoms of the disease. We found that the endogenous levels of 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine (8‐oxodG) in leukocytes DNA and excretion rates of urinary 8‐oxodG were significantly higher in the cancer patients than in the healthy carriers. Similarly, to the cancer patient group, 8‐oxodG level in leukocytes DNA is significantly higher in the carriers group in comparison with control group. That the control group comprised close relatives of the carriers gives further credit to our finding. Since we did not observe substantial differences in the analyzed markers of oxidative stress between the controls and the carriers, the observed increase in the level may be a result of a deficiency in the repair of 8‐oxodG. © 2009 UICC
Prostaglandin E2promotes cell proliferationviaprotein kinase C/extracellular signal regulated kinase pathway‐dependent induction of c‐Myc expression in human esophageal squamous cell carcinoma cells
Authors: Yu Le , Wu William Ka Kei , Li Zhi Jie , Li Hai Tao , Wu Ya Chun , Cho Chi Hin 
Published: May 2009

AbstractOverexpression of cyclooxygenase‐2 (COX‐2) and elevation of its derivative prostaglandin E2(PGE2) are implicated in human esophageal squamous cell carcinoma. The expression of c‐Myc, an oncogenic transcription factor, is also upregulated in this malignant disease. This study sought to elucidate whether a functional connection exists between COX‐2/PGE2and c‐Myc in esophageal squamous cell carcinoma. Results showed that PGE2substantially increased the proliferation of cultured esophageal squamous cell carcinoma cells. In this regard, PGE2substantially increased the mRNA and protein expression of c‐Myc and its association with the binding partner Max. Knockdown of c‐Myc by RNA interference also significantly attenuated PGE2‐induced cell proliferation. Further, mechanistic study revealed that PGE2increased the protein stability and nuclear accumulation of c‐Mycviaphosphorylation on serine 62 in an extracellular signal regulated kinase (ERK)‐dependent manner. To this end, ERK activation by PGE2was completely abolished by protein kinase C (PKC) inhibitors. Moreover, the effect of PGE2on c‐Myc expression was mimicked by EP2 receptor agonist. In addition, knockdown of EP2 receptor by EP2 siRNA attenuated PGE2‐induced c‐Myc expression. Collectively, our findings suggest that PGE2upregulates c‐Mycviathe EP2/PKC/ERK pathway. This study sheds new light on the carcinogenic mechanism of PGE2in esophageal squamous cell carcinoma. © 2009 UICC
Regulatory role of Sirt1 on the gene expression of fatty acid‐binding protein 3 in cultured porcine adipocytes
Authors: Shan Ti Z. , Ren Yang , Wu Ting , Liu Chen X. , Wang Yi Z. 
Published: May 2009

AbstractTo investigate whether Sirt1 could modulate fatty acid‐binding protein 3 (FABP3), we treated porcine adipocytes either with the Sirt1 inhibitor nicotinamide (NAM), with the Sirt1 activator resveratrol (RES), or by knockdown of Sirt1 by Sirt1‐siRNA. NAM or knockdown with Sirt1‐siRNA significantly inhibited Sirt1 mRNA expression, while increasing FABP3 mRNA levels. RES or RES + Sirt1‐siRNA treatments further proved that Sirt1 negatively regulated FABP3 gene expression in adipocytes. We also found a similar Sirt1 regulation pattern for PPARγ to that of FABP3 in adipocytes. Furthermore, NAM/RES + PPARγ‐siRNA treatments showed that Sirt1 may regulate the FABP3 gene expression partly through the PPARγ‐mediated signals. In summary, Sirt1 regulates the expression of FABP3 gene in adipocytes, and PPARγ apparently plays an important role in this process. J. Cell. Biochem. 107: 984–991, 2009. © 2009 Wiley‐Liss, Inc.
Runx and ThPOK: A balancing act to regulate thymocyte lineage commitment
Authors: Egawa Takeshi 
Published: May 2009

AbstractCD4‐positive helper T cells and CD8‐positive cytotoxic T cells comprise the majority of T lymphocytes present in secondary lymphoid organs and are essential for acquired immunity. These two populations are derived from common precursors in the thymus and selected through interaction between their clonal T‐cell receptors and major histocompatibility complex molecules. Although intensely studied as a model system for binary cell fate decisions, the mechanisms underlying the helper versus cytotoxic lineage choice in the thymus has been elusive. In the past few years, it has been demonstrated that the Runx family of transcription factors, particularly Runx3, is essential for the generation of cytotoxic lineage T cells, whereas the ThPOK zinc finger transcription factor that plays a crucial role in the differentiation of the helper lineage. Recent works have implied that a cross‐regulation between Runx and ThPOK contributes to appropriate thymocyte lineage commitment. In this article, recent findings on the transcription factor networks governing thymocyte lineage decisions are discussed, focusing on the two factors, and provide insights into mechanisms of lineage‐specific gene regulation in the process of T‐cell commitments. J. Cell. Biochem. 107: 1037–1045, 2009. © 2009 Wiley‐Liss, Inc.
Role of hypoxia in the hallmarks of human cancer
Authors: Ruan Kai , Song Gang , Ouyang Gaoliang 
Published: May 2009

AbstractHypoxia has been recognized as one of the fundamentally important features of solid tumors and plays a critical role in various cellular and physiologic events, including cell proliferation, survival, angiogenesis, immunosurveillance, metabolism, as well as tumor invasion and metastasis. These responses to hypoxia are at least partially orchestrated by activation of the hypoxia‐inducible factors (HIFs). HIF‐1 is a key regulator of the response of mammalian cells to oxygen deprivation and plays critical roles in the adaptation of tumor cells to a hypoxic microenvironment. Hypoxia and overexpression of HIF‐1 have been associated with radiation therapy and chemotherapy resistance, an increased risk of invasion and metastasis, and a poor clinical prognosis of solid tumors. The discovery of HIF‐1 signaling has led to a rapidly increasing understanding of the complex mechanisms involved in tumor hypoxia and has helped greatly in screening novel anticancer agents. In this review, we will first introduce the cellular responses to hypoxia and HIF‐1 signaling pathway in hypoxia, and then summarize the multifaceted role of hypoxia in the hallmarks of human cancers. J. Cell. Biochem. 107: 1053–1062, 2009. © 2009 Wiley‐Liss, Inc.
A stationary‐wave model of enzyme catalysis
Authors: Canepa Carlo 
Published: May 2009

AbstractAn expression for the external force driving a system of two coupled oscillators in the condensed phase was derived in the frame of the Debye theory of solids. The time dependence and amplitude of the force is determined by the size of the cell embedding the coupled oscillators and its Debye temperature (θD). The dynamics of the driven system of oscillators were followed in the two regimes of (a) low θD and cell diameter, as a model of liquid water, and (b) large θD and cell diameter, as a model of the core of a protein. The response in potential energy of the reference oscillator was computed for all possible values of the internal parameters of the system under investigation. For protein cores, the region in the parameter space of high maximum potential energy of the reference oscillator is considerably extended with respect to the corresponding simulation for water. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010
Hydrated germanium (II): Irregular structural and dynamical properties revealed by a quantum mechanical charge field molecular dynamics study
Authors: Azam S. Sikander , Lim Len Herald V. , Hofer Thomas S. , Randolf Bernhard R. , Rode Bernd M. 
Published: May 2009

AbstractStructural and dynamical properties of Ge (II) in aqueous solution have been investigated using the novel ab initio quantum mechanical charge field (QMCF) molecular dynamics (MD) formalism. The first and second hydration shells were treated by ab initio quantum mechanics at restricted Hartree–Fock (RHF) level using the cc‐pVDZ‐PP basis set for Ge (II) and Dunning double‐ζ plus polarization basis sets for O and H. Besides ligand exchange processes and mean ligand residence times to observe dynamics, tilt‐ and theta‐angle distributions along with an advanced structural parameter, namely radial and angular distribution functions (RAD) for different regions were also evaluated. The combined radial and angular distribution depicted through surface plot and contour map is presented to provide a detailed insight into the density distribution of water molecules around the Ge2+ ion. A strongly distorted hydration structure with two trigonal pyramidal substructures within the first hydration shell is observed, which demonstrates the lone‐pair influence and provides a new basis for the interpretation of the catalytic and pharmacological properties of germanium coordination compounds. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010
Non‐Born–Oppenheimer dynamics calculations using the coherent switching with decay of mixing method
Authors: Li Bin , Chu Tian‐Shu , Han Ke‐Li 
Published: May 2009

AbstractA theoretical investigation of the nonadiabatic processes that are involved in the full three‐dimensional D+H2, H+D2, D++H2, and H++D2 reaction systems has been performed using the method of coherence switching with decay of mixing (CSDM) developed by Truhlar and coworkers. The electronic density matrix for each trajectory is fully coherent in the CSDM method, and a switching algorithm different to the original “decay of mixing” method is used to determine the pure state toward which the decoherent force drives the system. By solving the equations for the evolution of the electronic state populations along the semiclassical trajectory, the ensemble can present effective physical insight into nonadiabatic dynamics. The calculations for the D+H2 and H+D2 systems is based on the double many body expansion potential energy surface. The potential energy surface constructed by Kamisaka et al. is employed in the calculation of D++H2 and H++D2 reactions. The cross sections and the reaction probabilities for the total angular momentum J = 0 are calculated for all of these systems. The calculated results from the CSDM method are in good agreement with exact quantum mechanical calculations and experimental measurements. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010
The heparan sulfate proteoglycan (HSPG) glypican‐3 mediates commitment of MC3T3‐E1 cells toward osteogenesis
Authors: Haupt Larisa M. , Murali Sadasivam , Mun Foong Kin , Teplyuk Nadiya , Mei Leong Fong , Stein Gary S. , van Wijnen Andre J. , Nurcombe Victor , Cool Simon M. 
Published: May 2009

AbstractHeparan sulfate (HS) sugar chains attached to core proteoglycans (PGs) termed HSPGs mediate an extensive range of cell–extracellular matrix (ECM) and growth factor interactions based upon their sulfation patterns. When compared with non‐osteogenic (maintenance media) culture conditions, under established osteogenic culture conditions, MC3T3‐E1 cells characteristically increase their osteogenic gene expression profile and switch their dominant fibroblast growth factor receptor (FGFR) from FGFR1 (0.5‐fold decrease) to FGFR3 (1.5‐fold increase). The change in FGFR expression profile of the osteogenic‐committed cultures was reflected by their inability to sustain an FGF‐2 stimulus, but respond to BMP‐2 at day 14 of culture. The osteogenic cultures decreased their chondroitin and dermatan sulfate PGs (biglycan, decorin, and versican), but increased levels of the HS core protein gene expression, in particular glypican‐3. Commitment and progress through osteogenesis is accompanied by changes in FGFR expression, decreased GAG initiation but increased N‐ and O‐sulfation and reduced remodeling of the ECM (decreased heparanase expression) resulting in the production of homogenous (21 kDa) HS chain. With the HSPG glypican‐3 expression strongly upregulated in these processes, siRNA was used to knockdown this gene to examine the effect on osteogenic commitment. Reduced glypican‐3 abrogated the expression of Runx2, and thus differentiation. The reintroduction of this HSPG into Runx2‐null cells allowed osteogenesis to proceed. These results demonstrate the dependence of osteogenesis on specific HS chains, in particular those associated with glypican‐3. J. Cell. Physiol. 220: 780–791, 2009. © 2009 Wiley‐Liss, Inc.
Stepwise up‐regulation of MicroRNA expression levels from replicating to reversible and irreversible growth arrest states in WI‐38 human fibroblasts
Authors: Maes Olivier C. , Sarojini Harshini , Wang Eugenia 
Published: May 2009

AbstractMicroRNAs (miRNAs) are small non‐coding RNAs that regulate diverse genetic expression networks through their control of mRNA stability or translation. Their role in aging mechanisms has been proposed in various model systems. In this report, the expression profiling of 462 human miRNAs in the reversible growth arrest state of quiescence, and irreversible states of replicative senescence and hydrogen peroxide‐induced premature senescence, are compared to young replicating lung fibroblasts. Greater numbers of up‐regulated than down‐regulated miRNAs are observed when cells stop proliferating, particularly in premature senescence, somewhat less in replicative senescence, and less still in quiescence. Several altered miRNA expressions are shared by the three growth arrest states, including the up‐regulation of miR‐34a, ‐624, ‐638 and miR‐377, and the down‐regulation of miR‐365 and miR‐512‐5p. miRNAs up‐regulated in both permanent growth arrest states but not in quiescence include let‐7g, miR‐26a, ‐136, ‐144, ‐195 and miR‐200b. In each of the growth arrest states, miR‐34a and let‐7f have the most robust up‐regulation in H2O2‐induced premature senescence, followed by miR‐638 and miR‐663 in replicative senescence, and finally, miR‐331‐3p and miR‐595 in quiescence. Our comprehensive evaluation of miRNA target correlations with known biomarkers for replicative senescence suggests that miRNAs may repress pathways controlling not only cell cycle traverse and proliferation, but also insulin‐like signaling, DNA repair and apoptosis, all of which are cellular functions deficient in senescent human fibroblasts. J. Cell. Physiol. 221: 109–119, 2009. © 2009 Wiley‐Liss, Inc
Osteopontin increases migration and MMP‐9 up‐regulation via αvβ3 integrin, FAK, ERK, and NF‐κB‐dependent pathway in human chondrosarcoma cells
Authors: Chen Ying‐Ju , Wei Ying‐Ying , Chen Hsien‐Te , Fong Yi‐Chin , Hsu Chin‐Jung , Tsai Chun‐Hao , Hsu Horng‐Chaung , Liu Shing‐Hwa , Tang Chih‐Hsin 
Published: May 2009

AbstractTumor malignancy is associated with several features such as proliferation ability and frequency of metastasis. Osteopontin (OPN), which abundantly expressed in bone matrix, is involved in cell adhesion, migration, invasion and proliferation via interaction with its receptor, that is, αvβ3 integrin. However, the effect of OPN on migration activity in human chondrosarcoma cells is mostly unknown. Here we found that OPN increased the migration and expression of matrix metalloproteinase (MMP)‐9 in human chondrosarcoma cells (JJ012 cells). RGD peptide, αvβ3 monoclonal antibody and MAPK kinase (MEK) inhibitors (PD98059 and U0126) but not RAD peptide inhibited the OPN‐induced increase of the migration and MMP‐9 up‐regulation of chondrosarcoma cells. OPN stimulation increased the phosphorylation of focal adhesion kinase (FAK), MEK and extracellular signal‐regulated kinase (ERK). In addition, treatment of JJ012 cells with NF‐κB inhibitor (PDTC) or IκB protease inhibitor (TPCK) inhibited OPN‐induced cell migration and MMP‐9 up‐regulation. Stimulation of JJ012 cells with OPN also induced IκB kinase α/β (IKK α/β) phosphorylation, IκBα phosphorylation, p65 Ser536 phosphorylation, and κB‐luciferase activity. The OPN‐mediated increases in MMP‐9 and κB‐luciferase activities were inhibited by RGD peptide, PD98059 or FAK and ERK2 mutant. Taken together, our results indicated that OPN enhances the migration of chondrosarcoma cells by increasing MMP‐9 expression through the αvβ3 integrin, FAK, MEK, ERK and NF‐κB signal transduction pathway. J. Cell. Physiol. 221: 98–108, 2009. © 2009 Wiley‐Liss, Inc
First‐trimester prenatal sonographic diagnosis of ectopia cordis in a twin gestation
Authors: Barbee Kristen , Wax Joseph R. , Pinette Michael G. , Cartin Angelina , Blackstone Jacquelyn 
Published: May 2009

AbstractThe 11–14‐week ultrasound examination allows early pregnancy dating, detection of major anomalies and multiple gestations, and accurate chorionicity determination. We describe a rare case of first‐trimester sonographic diagnosis of ectopia cordis in a dichorionic twin pregnancy, illustrating the benefits of early ultrasound in patient counseling and management. © 2009 Wiley Periodicals, Inc. J Clin Ultrasound, 2009