bluuebunny/crossref_metadata_2025_split huggingface dataset:
Up-Regulation of the Fibroblast Growth Factor 8 Subfamily in Human Hepatocellular Carcinoma for Cell Survival and Neoangiogenesis Δσ
Authors: Gauglhofer Christine , Sagmeister Sandra , Schrottmaier Waltraud , Fischer Carina , Rodgarkia-Dara Chantal , Mohr Thomas , Stättner Stefan , Bichler Christoph , Kandioler Daniela , Wrba Fritz , Schulte-Hermann Rolf , Holzmann Klaus , Grusch Michael , Marian Brigitte , Berger Walter , Grasl-Kraupp Bettina 
Published: December 2010

Abstract

Fibroblast growth factors (FGFs) and their high-affinity receptors [fibroblast growth factor receptors (FGFRs)] contribute to autocrine and paracrine growth stimulation in several nonliver cancer entities. Here we report that at least one member of the FGF8 subfamily (FGF8, FGF17, and FGF18) was up-regulated in 59% of 34 human hepatocellular carcinoma (HCC) samples that we investigated. The levels of the corresponding receptors (FGFR2, FGFR3, and FGFR4) were also elevated in the great majority of the HCC cases. Overall, 82% of the HCC cases showed overexpression of at least one FGF and/or FGFR. The functional implications of the deregulated FGF/FGFR system were investigated by the simulation of an insufficient blood supply. When HCC-1.2, HepG2, or Hep3B cells were subjected to serum withdrawal or the hypoxia-mimetic drug deferoxamine mesylate, the expression of FGF8 subfamily members increased dramatically. In the serum-starved cells, the incidence of apoptosis was elevated, whereas the addition of FGF8, FGF17, or FGF18 impaired apoptosis, which was associated with phosphorylation of extracellular signal-regulated kinase 1/2 and ribosomal protein S6. In contrast, down-modulation of FGF18 by small interfering RNA (siRNA) significantly reduced the viability of the hepatocarcinoma cells. siRNA targeting FGF18 also impaired the cells' potential to form clones at a low cell density or in soft agar. With respect to the tumor microenvironment, FGF17 and FGF18 stimulated the growth of HCC-derived myofibroblasts, and FGF8, FGF17, and FGF18 induced the proliferation and tube formation of hepatic endothelial cells.

Conclusion:

FGF8, FGF17, and FGF18 are involved in autocrine and paracrine signaling in HCC and enhance the survival of tumor cells under stress conditions, malignant behavior, and neoangiogenesis. Thus, the FGF8 subfamily supports the development and progression of hepatocellular malignancy. (Hepatology 2011)
Early exercise promotes positive hippocampal plasticity and improves spatial memory in the adult life of rats
Authors: Gomes da Silva Sérgio , Unsain Nicolas , Mascó Daniel Hugo , Toscano‐Silva Michelle , de Amorim Henrique Alves , Silva Araújo Bruno Henrique , Simões Priscila Santos Rodrigues , da Graça Naffah‐Mazzacoratti Maria , Mortara Renato Arruda , Scorza Fulvio Alexandre , Cavalheiro Esper Abrão , Arida Ricardo Mario 
Published: December 2010

AbstractThere is a great deal of evidence showing the capacity of physical exercise to enhance cognitive function, reduce anxiety and depression, and protect the brain against neurodegenerative disorders. Although the effects of exercise are well documented in the mature brain, the influence of exercise in the developing brain has been poorly explored. Therefore, we investigated the morphological and functional hippocampal changes in adult rats submitted to daily treadmill exercise during the adolescent period. Male Wistar rats aged 21 postnatal days old (P21) were divided into two groups: exercise and control. Animals in the exercise group were submitted to daily exercise on the treadmill between P21 and P60. Running time and speed gradually increased over this period, reaching a maximum of 18 m/min for 60 min. After the aerobic exercise program (P60), histological and behavioral (water maze) analyses were performed. The results show that early‐life exercise increased mossy fibers density and hippocampal expression of brain‐derived neurotrophic factor and its receptor tropomyosin‐related kinase B, improved spatial learning and memory, and enhanced capacity to evoke spatial memories in later stages (when measured at P96). It is important to point out that while physical exercise induces hippocampal plasticity, degenerative effects could appear in undue conditions of physical or psychological stress. In this regard, we also showed that the exercise protocol used here did not induce inflammatory response and degenerating neurons in the hippocampal formation of developing rats. Our findings demonstrate that physical exercise during postnatal development results in positive changes for the hippocampal formation, both in structure and function. © 2010 Wiley Periodicals, Inc.
Early life stress stimulates hippocampal reelin gene expression in a sex‐specific manner: Evidence for corticosterone‐mediated action
Authors: Gross Claus M. , Flubacher Armin , Tinnes Stefanie , Heyer Andrea , Scheller Marie , Herpfer Inga , Berger Mathias , Frotscher Michael , Lieb Klaus , Haas Carola A. 
Published: December 2010

AbstractEarly life stress predisposes to the development of psychiatric disorders. In this context the hippocampal formation is of particular interest, because it is affected by stress on the structural and cognitive level. Since little is known how early life stress is translated on the molecular level, we mimicked early life stress in mouse models and analyzed the expression of the glycoprotein Reelin, a master molecule for development and differentiation of the hippocampus. From postnatal day 1 (P1) to P14, mouse pups were subjected to one of the following treatments: nonhandling (NH), handling (H), maternal separation (MS), and early deprivation (ED) followed by immediate (P15) or delayed (P70) real time RT‐PCR analysis of reelin mRNA expression. We show that at P15, reelin mRNA levels were significantly increased in male H and ED groups when compared with the NH group. In contrast, no stress‐induced alterations of reelin mRNA expression were found in female animals. This sex difference in stress‐mediated stimulation of reelin expression was maintained into adulthood, since at P70 intergroup differences were still found in male, but not in female mice. On the cellular level, however, we did not find any significant differences in cell densities of Reelin‐immunolabeled neurons between treatment groups or sexes, but an overall reduction of Reelin‐expressing neurons in the adult hippocampus when compared to P15. To address the question whether corticosterone mediates the stress‐induced up‐regulation of reelin gene expression, we used age‐matched hippocampal slice cultures derived from male and female mouse pups. Quantitative determination of mRNA levels revealed that corticosterone treatment significantly up‐regulated reelin mRNA expression in male, but not in female hippocampi. Taken together, these results show a sex‐specific regulation of reelin gene expression by early life experience, most likely mediated by corticosterone. © 2010 Wiley Periodicals, Inc.
Effect of endothelial cells on bone regeneration using poly(L‐lactide‐co‐1,5‐dioxepan‐2‐one) scaffolds
Authors: Xing Zhe , Xue Ying , Dånmark Staffan , Schander Kerstin , Østvold Siren , Arvidson Kristina , Hellem Sølve , Finne‐Wistrand Anna , Albertsson Ann‐Christine , Mustafa Kamal 
Published: December 2010

AbstractOur recentin vitrostudy demonstrated that endothelial cells (ECs) might influence the differentiation of bone marrow stromal cells (BMSCs). Therefore, the aim of this study was to describe this effectin vivo, using a rat calvarial bone defect model. BMSCs were isolated from femurs of two‐donor Lewis rats and expanded in α‐minimum essential medium containing 10% fetal bovine serum. One fifth of BMSCs were induced and differentiated into ECs in an Endothelial Cell Growth Medium‐2 and then characterized by a flow cytometry. The remaining BMSCs were cultured in freshly prepared osteogenic stimulatory medium, containing dexamethasone, ascorbic acid and β‐glycerophosphate. Either BMSCs alone (BMSC‐group) or co‐cultured ECs/BMSCs (CO‐group) were seeded into poly(L‐lactide‐co‐1,5‐dioxepan‐2‐one) [poly(LLA‐co‐DXO)] scaffolds, cultured in spinner flasks, and then implanted into symmetrical calvarial defects prepared in recipient rats. The animals were sacrificed after 2 months. The formation of new bone was evaluated by radiography and histology and by the expression of osteogenic markers using reverse transcriptase‐polymerized chain reaction (RT–PCR). To investigate vessel formation, histological staining was performed with EC's markers. The radiographical and histological results showed more rapid bone formation in the CO‐ than in the BMSC‐group. However, the expression of EC's marker was similar on both groups by histological analysis after 2 months postoperatively. Furthermore, the CO‐group exhibited greater expression of osteogenic markers as demonstrated by RT–PCR. The results are consistent with the previousin vitrofindings that poly(LLA‐co‐DXO) scaffold might be suitable candidate for bone tissue engineering.In vivo, bone regeneration was enhanced by a construct of the polymer scaffold loaded with co‐cultured cells. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Mineral trioxide aggregate solution inhibits osteoclast differentiation through the maintenance of osteoprotegerin expression in osteoblasts
Authors: Hashiguchi Daisuke , Fukushima Hidefumi , Nakamura Midori , Morikawa Kazumasa , Yasuda Hisataka , Udagawa Nobuyuki , Maki Kenshi , Jimi Eijiro 
Published: December 2010

AbstractMineral trioxide aggregate (MTA) is a therapeutic, endodontic repair material that is reported to exhibit calcified tissue‐conductive activity. The aim of this study was to investigate whether MTA may prevent osteoclast differentiation in vitro. MTA solution, but not other commonly used retrofilling materials, such as Dycal, Super‐EBA, or intermediate restorative material (IRM) solution, dose‐dependently inhibited osteoclastogenesis in cocultures of mouse bone marrow cells (BMCs) with primary osteoblast cells (POBs) induced by 1α,25‐dihydroxyvitamin D3 [1α,25(OH)2D3]. Exogenous CaCl2 medium supplementation did not inhibit osteoclastogenesis in cocultures. Furthermore, MTA solution did not affect receptor activator of NF‐κB ligand (RANKL)‐induced osteoclastogenesis, suggesting that POBs are targets of MTA. MTA solution suppressed the 1α,25(OH)2D3‐induced reduction of osteoprotegerin (OPG) mRNA and protein production without changing RANKL expression in POBs. Consistent with this result, MTA solution did not inhibit osteoclastogenesis in cocultures of BMCs and POBs from OPG‐deficient mice. Therefore, the maintenance of OPG expression in POBs appears to be critical for the inhibitory effect of MTA solution on osteoclast differentiation. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Hematopoietic progenitor cell count, but not immature platelet fraction value, predicts successful harvest of autologous peripheral blood stem cells
Authors: Mitani Noriyuki , Yujiri Toshiaki , Tanaka Yoshinori , Tanaka Mayumi , Fujii Yasuhiko , Hinoda Yuji , Tanizawa Yukio 
Published: December 2010

AbstractMobilized stem cells in the peripheral blood (PB) must be efficiently harvested at the appropriate time before autologous PB stem cell (PBSC) transplantation. Enumeration of CD34+ cells in the PB before apheresis predicts the number of PBSCs that can be collected, but the cytometric techniques used are complex and expensive. Therefore, it is necessary to identify an alternative to the CD34+ cell count in PBSC harvest‐time monitoring. Fully automated flow cytometry using blood cell counters now allows reliable quantification of immature myeloid cells in the PB, referred to as hematopoietic progenitor cells (HPC), and reticulated platelets, expressed as the immature platelet fraction (IPF). Immature or reticulated platelets are thought to correlate with thrombopoietic activity of the marrow. Following a chemotherapy nadir, the recovery of white blood cell and platelet counts has been used to determine the right time for apheresis. Therefore, we examined whether the HPC count and IPF value could be used to predict PBSC mobilization in 20 patients with hematological malignancies. The HPC count was found to be correlated with the CD34+ cell count (r = 0.84, P < 0.01), whereas the IPF value was not (r = 0.37, P = 0.44). Therefore, the HPC count, but not the IPF value, is a possible predictor of the timing of autologous stem cell transplantation. J. Clin. Apheresis, 2011. © 2010 Wiley‐Liss, Inc.
Stem and progenitor cells for neurological repair: Minor issues, major hurdles, and exciting opportunities for paracrine‐based therapeutics
Authors: Shimada Issei S. , Spees Jeffrey L. 
Published: December 2010

AbstractThe transplantation of cultured stem and progenitor cells is a key element in the rapidly growing field of regenerative medicine. Based on their ability to rescue and/or repair injured tissue and partially restore organ function, multiple types of stem/progenitor cells have already entered into clinical trials. However, despite several decades of intense research, the goal to apply culture‐expanded stem/progenitor cells in a manner that can effectively replace cells after injury has yet to be realized. Many sources of potentially useful cells are available, but something is clearly missing. In addition, recent studies suggest that paracrine effects of secreted or released factors are responsible for most of the benefits observed after cell transplantation, rather than direct cell replacement. These data call into question the need for cell transplantation for many types of therapy, in particular for acute injuries such as myocardial infarction and stroke. In this review, we examine current progress in the area of cell transplantation and minor issues and major hurdles regarding the clinical application of different cell types. We discuss the “paracrine hypothesis” for the action of transplanted stem/progenitor cells as an opportunity to identify defined combinations of biomolecules to rescue and/or repair tissues after injury. Although many of the concepts in this review will apply to multiple injury/repair systems, we will focus primarily on stem/progenitor cell‐based treatments for neurological disorders and stroke. J. Cell. Biochem. 112: 374–380, 2011. © 2010 Wiley‐Liss, Inc.
New insights into the inactivation of gastric tumor suppressor RUNX3: The role of H. pylori infection
Authors: Tsang Ying‐Hung Nicole , Lamb Acacia , Chen Lin‐Feng 
Published: December 2010

AbstractRunt‐related transcription factor 3, or RUNX3, is a tumor suppressor in gastric cancer. Inactivation of RUNX3 is causally associated with the genesis of gastric cancer, since RUNX3 is frequently inactivated in gastric cancers by hemizygous deletion, hypermethylation of its promoter, or protein mislocalization. Infection with Helicobacter pylori is the strongest risk factor for the development of gastric cancer. Recent studies have indicated that H. pylori infection plays an important role in the inactivation of RUNX3, and that this inactivation contributes to the pathogenesis of H. pylori. Here we summarize these recent advances and discuss their significances in understanding the initiation and development of gastric cancer. J. Cell. Biochem. 112: 381–386, 2011. © 2010 Wiley‐Liss, Inc.
Phloroglucinol derivative MCPP induces cell apoptosis in human colon cancer
Authors: Huang Ssu‐Ming , Cheung Chi‐Wai , Chang Chih‐Shiang , Tang Chih‐Hsin , Liu Ju‐Fang , Lin Yu‐Hsin , Chen Jia‐Hong , Ko Shihi‐Hsun , Wong Kar‐Lok , Lu Dah‐Yuu 
Published: December 2010

AbstractThis study is the first to investigate the anticancer effects of the new phloroglucinol derivative (3,6‐bis(3‐chlorophenylacetyl)phloroglucinol; MCPP) in human colon cancer cells. MCPP induced cell death and antiproliferation in three human colon cancer, HCT‐116, SW480, and Caco‐2 cells, but not in primary human dermal fibroblast cells. MCPP‐induced concentration‐dependent apoptotic cell death in colon cancer cells was measured by fluorescence‐activated cell sorter (FACS) analysis. Treatment of HCT‐116 human colon cancer cells with MCPP was found to induce a number of signature endoplasmic reticulum (ER) stress markers; and up‐regulation of CCAAT/enhancer‐binding protein homologous protein (CHOP) and glucose‐regulated protein (GRP)‐78, phosphorylation of eukaryotic initiation factor‐2α (eIF‐2α), suggesting the induction of ER stress. MCPP also increased GSK3α/β(Tyr270/216) phosphorylation and reduced GSK3α/β(Ser21/9) phosphorylation time‐dependently. Transfection of cells with GRP78 or CHOP siRNA, or treatment of GSK3 inhibitor SB216163 reduced MCPP‐mediated cell apoptosis. Treatment of MCPP also increased caspase‐7, caspase‐9, and caspase‐3 activity. The inhibition of caspase activity by z‐DEVE‐FMK or z‐VAD‐FMK significantly reduced MCPP‐induced apoptosis. Furthermore, treatment of GSK3 inhibitor SB216763 also dramatically reversed MCPP‐induced GRP and CHOP up‐regulation, and pro‐caspase‐3 and pro‐caspase‐9 degradation. Taken together, the present study provides evidences to support that GRP78 and CHOP expression, and GSK3α/β activation in mediating the MCPP‐induced human colon cancer cell apoptosis. J. Cell. Biochem. 112: 643–652, 2011. © 2010 Wiley‐Liss, Inc.
Direct transcriptional targets of sex steroid hormones in bone
Authors: Krum Susan A. 
Published: December 2010

AbstractThe sex steroid hormones, androgens and estrogens, via their respective nuclear receptors, regulate bone mineral density in humans and mice. Very little is known about the direct targets of the androgen and estrogen receptors in bone cells. First, models of hormone and receptor deficiency in mouse and human bone are discussed. This review then focuses on the direct targets of the receptors in osteoblasts and osteoclasts. A direct target of a NR is defined here as a gene that is regulated by NR binding to the DNA (either through DNA binding or association with a DNA binding protein) at an enhancer or promoter of that gene. The experimental evidence that illustrates androgen and estrogen gene regulation in osteoblasts and osteoclasts will be summarized and compared with the phenotype of the hormones in vivo. J. Cell. Biochem. 112: 401–408, 2011. © 2011 Wiley‐Liss, Inc.
Key roles of histone methyltransferase and demethylase in leukemogenesis
Authors: Yoshimi Akihide , Kurokawa Mineo 
Published: December 2010

AbstractA growing body of evidence has underlined the involvement of histone methyltransferases and demethylases in leukemia development. These findings can be roughly classified into two categories according to their association with leukemia. On the one hand, these histone modifiers are recruited to DNA by specific affinities of aberrantly expressed transcription factors or fusion proteins, and induce chromatin modifications to regulate target gene expression. Epigenetic regulators may function as oncogenes in this context. On the other hand, recent studies have identified inactivating mutations of some key histone modulators in myeloid malignancies and these results suggest that they act as tumor suppressors. Profound understanding of these findings in the two categories will help us consider clinical applications of epigenetic drugs. In this prospect we will review the leukemogenic mechanisms clarified by the epigenetic approach and the current findings on genetic aberrations in each methyltransferase or demethylase, and discuss the potential of medical intervention in leukemia or leukemia stem cells targeting histone modifiers. J. Cell. Biochem. 112: 415–424, 2011. © 2010 Wiley‐Liss, Inc.
Molecular mechanisms underlying the inhibition of IFN‐γ‐induced, STAT1‐mediated gene transcription in human macrophages by simvastatin and agonists of PPARs and LXRs
Authors: Li Na , Salter Rebecca C. , Ramji Dipak P. 
Published: December 2010

AbstractPPARs and LXRs are ligand‐activated transcription factors that are emerging as promising therapeutic targets for limiting atherosclerosis, an inflammatory disorder orchestrated by cytokines. The potent anti‐atherogenic actions of these nuclear receptors involve the regulation of glucose and lipid metabolism along with attenuation of the inflammatory response. Similarly, cholesterol‐lowering drugs, statins, inhibit inflammation. Unfortunately, the mechanisms underlying such inhibitory actions of these agents in human macrophages are poorly understood and were therefore investigated in relation to IFN‐γ, a key pro‐atherogenic cytokine, which mediates its cellular effects mainly through STAT1. Simvastatin and PPAR agonists had no effect on the IFN‐γ‐induced, phosphorylation‐mediated activation of STAT1 and its DNA binding but attenuated its ability to activate gene transcription. On the other hand, LXR activators attenuated both DNA binding and trans‐activation potential of STAT1 induced by IFN‐γ. These studies reveal differences in the mechanism of action of agonists of PPARs (and simvastatin) and LXRs on the IFN‐γ‐induced, STAT1‐mediated gene transcription in human macrophages. J. Cell. Biochem. 112: 675–683, 2011. © 2010 Wiley‐Liss, Inc.
Modulation of oxidative stress responses in the human retinal pigment epithelium following treatment with vitamin C
Authors: Yin Jinggang , Thomas Fridtjof , Lang John C. , Chaum Edward 
Published: December 2010

AbstractOxidative stress (OS) in the retina plays an important role in the development and progression of age‐related macular degeneration (AMD). Our previous work has shown that OS can quantitatively regulate the expression of AP‐1 family genes in the retinal pigment epithelium (RPE). In this study, we sought to determine whether AP‐1 genes can be used as cellular biomarkers of OS to evaluate the efficacy of ascorbate, the major aqueous‐phase antioxidant in the blood, in reducing OS in RPE cells in vitro. Human ARPE19 cells were pretreated with increasing levels of ascorbate (0–500 µM) for 3 days which was then removed from the medium. OS was induced 24 h later by the addition of hydrogen peroxide for 1–4 h, to bring the final media concentration of H2O2 to 500 µM. FosB, c‐Fos, and ATF3 gene expression was examined from 0 to 24 h after OS. Pretreatment with 200 µM ascorbate maximally reduced the transcriptional OS response of AP‐1 genes by up to 87% after 1 and 4 h, compared to controls. One hundred micromolar of ascorbate provided a statistically significant, but far more modest effect. Ascorbate supplementation of 100–200 µM appears to strongly inhibit OS‐induced activation of AP‐1 in vitro, but pretreatment with higher levels of ascorbate conferred no additional advantage. These studies suggest that there are optimal levels of antioxidant supplementation to the RPE in vitro. Laboratory assays based upon transcription factor biomarkers may be useful to define beneficial molecular responses to new antioxidants, alternative dosing regimens, and to explore therapeutic efficacy in OS models in vitro. J. Cell. Physiol. 226: 2025–2032, 2011. © 2010 Wiley‐Liss, Inc.