bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular transformation by cigarette smoke extract involves alteration of glycolysis and mitochondrial function in esophageal epithelial cells
Authors: Kim Myoung Sook , Huang Yiping , Lee Juna , Zhong Xiaoli , Jiang Wei‐Wen , Ratovitski Edward A. , Sidransky David 
Published: November 2009

AbstractCigarette‐smoking increases the risk of developing various types of human cancers including esophageal cancers. To test the effects of chronic cigarette smoke exposure directly on esophageal epithelium, cellular resistance to mainstream extract (MSE), or sidestream smoke extract (SSE) was developed in chronically exposed nonmalignant Het‐1A cells. Anchorage‐independent growth, in vitro invasion capacity and proliferation of the resistant cells increased compared with the unexposed, sensitive cells. An epithelial marker E‐cadherin was down‐regulated and mesenchymal markers N‐cadherin and vimentin were up‐regulated in the resistant cells. Het‐1A cells resistant to MSE or SSE consumed more glucose, and produced more lactate than the sensitive cells. The increased anchorage‐independent cell growth of the resistant cells was suppressed by a glycolysis inhibitor, 2‐deoxy‐D‐glucose, indicating that these cells are highly dependent on the glycolytic pathway for survival. Decreased mitochondrial membrane potential and ATP production in the resistant cells indicate the presence of mitochondrial dysfunction induced by chronic exposure of cigarette smoke extract. Increased expression of nuclear genes in the glycolytic pathway and decreased levels of mitochondrial genes in the resistant cells support the notion that cigarette smoking significantly contributes to the transformation of nonmalignant esophageal epithelial cells into a tumorigenic phenotype.
NY‐CO‐58/KIF2C is overexpressed in a variety of solid tumors and induces frequent T cell responses in patients with colorectal cancer
Authors: Gnjatic Sacha , Cao Yanran , Reichelt Uta , Yekebas Emre F. , Nölker Christina , Marx Andreas H. , Erbersdobler Andreas , Nishikawa Hiroyoshi , Hildebrandt York , Bartels Katrin , Horn Christiane , Stahl Tanja , Gout Ivan , Filonenko Valeriy , Ling Khoon‐Lin , Cerundolo Vincenzo , Luetkens Tim , Ritter Gerd , Friedrichs Kay , Leuwer Rudolf , Hegewisch‐Becker Susanna , Izbicki Jakob R. , Bokemeyer Carsten , Old Lloyd J. , Atanackovic Djordje 
Published: November 2009

AbstractNY‐CO‐58/KIF2C has been identified as a tumor antigen by screening antibody responses in patients with colorectal cancer. However, expression had not consequently been examined, and nothing was known about its ability to induce spontaneous T cell responses, which have been suggested to play a role in the development of colorectal cancer. We analyzed 5 colorectal cancer cell lines, and tumor samples and adjacent healthy tissues from 176 patients with epithelial cancers for the expression of NY‐CO‐58/KIF2C by RT‐PCR and Western Blot. T cell responses of 43 colorectal cancer patients and 35 healthy donors were evaluated by ELISpot following stimulation with 30mer peptides or full‐length protein. All cell lines and tumor samples from colorectal cancer patients expressed NY‐CO‐58/KIF2C on the protein and RNA level, and expression levels correlated strongly with Ki‐67 expression (r = 0.69; p = 0.0003). Investigating NY‐CO‐58/KIF2C‐specific T cell responses, CD8+ T cells directed against 1 or more peptides were found in less than 10% of patients, whereas specific CD4+ T cells were detected in close to 50% of patients. These T cells were of high avidity, recognized the naturally processed antigen and secreted IFN‐γ and TNF‐α. Depletion of CD4+CD25+ T cells before stimulation significantly increased the intensity of the preexisting response. NY‐CO‐58/KIF2C is significantly overexpressed in colorectal and other epithelial cancers and expression levels correlate with the proliferative activity of the tumor. Importantly, NY‐CO‐58/KIF2C was able to induce spontaneous CD4+ T cell responses of the Th1‐type, which were tightly controlled by peripheral T regulatory cells.
Betulinic acid suppresses STAT3 activation pathway through induction of protein tyrosine phosphatase SHP‐1 in human multiple myeloma cells
Authors: Pandey Manoj K. , Sung Bokyung , Aggarwal Bharat B. 
Published: November 2009

AbstractSTAT3 activation has been associated with survival, proliferation and invasion of various human cancers. Whether betulinic acid, a pentacyclic triterpene, can modulate the STAT3 pathway, was investigated in human multiple myeloma (MM) cells. We found that betulinic acid inhibited constitutive activation of STAT3, Src kinase, JAK1 and JAK2. Pervanadate reversed the betulinic acid‐induced downregulation of STAT3 activation, suggesting the involvement of a protein tyrosine phosphatase (PTP). Furthermore, betulinic acid induced the expression of the PTP SHP‐1 and silencing of the SHP‐1 gene abolished the ability of betulinic acid to inhibit STAT3 activation and rescued betulinic acid‐induced cell death. Betulinic acid also downregulated the expression of STAT3‐regulated gene products such as bcl‐xL, bcl‐2, cyclin D1 and survivin. This correlated with an increase in apoptosis as indicated by an increase in the sub‐G1 cell population and an increase in caspase‐3‐induced PARP cleavage. Consistent with these results, overexpression of constitutive active STAT3 significantly reduced the betulinic acid‐induced apoptosis. Betulinic acid also enhanced the apoptosis induced by thalidomide (from 10 to 55%) and bortezomib (from 5 to 70%) in MM cells. Overall, our results suggest that betulinic acid downregulates STAT3 activation through upregulation of SHP‐1, and this may have potential in sensitization of STAT3 overexpressing tumors to chemotherapeutic agents.
Tumor‐stromal crosstalk in invasion of oral squamous cell carcinoma: a pivotal role of CCL7
Authors: Jung Da‐Woon , Che Zhong Min , Kim Jinmi , Kim Kyungshin , Kim Ki‐Yeol , Williams Darren , Kim Jin 
Published: November 2009

AbstractRecent studies have shown that stromal fibroblasts have a more profound influence on the initiation and progression of carcinoma than was previously appreciated. This study aimed at investigating the reciprocal relationship between cancer cells and their associated fibroblasts at both the molecular and cellular level in oral squamous cell carcinoma (OSCC). To identify key molecular regulators expressed by carcinoma‐associated fibroblasts (CAF) that promote cancer cell invasion, microarrays were performed by comparing cocultured OSCC cells and CAF with monoculture controls. Microarray and real‐time PCR analysis identified marked upregulation of the chemokine (C‐C motif) ligand 7 (CCL7) in cocultured CAF. ELISA showed an elevated level of CCL7 secretion from CAF stimulated by coculture with OSCC cells. CCL7 promoted the invasion and migration of OSCC cells, and the invasiveness was inhibited by treatment with CCL7 neutralizing antibody. OSCC cells were shown to express CCR1, CCR2 and CCR3, receptors for CCL7, by RT‐PCR. In addition, treatment with anti‐CCR1 or anti‐CCR3 antibody inhibited CCL7‐induced OSCC cell migration, implicating that CCL7 promotes cancer cell migration through CCR1 and CCR3 on OSCC cells. Cytokine antibody array analysis of the supernatant from OSCC cell culture revealed that interleukin‐1α was an inducer of CCL7 secretion by CAF. This study confirms the reciprocal relationship of the molecular crosstalk regulating the invasion of OSCC and describes new potential targets for future therapy.
Recombinant single‐chain variable fragment antibodies against extracellular epitopes of human multidrug resistance protein MRP3 for targeting malignant gliomas
Authors: Kuan Chien‐Tsun , Srivastava Nidhi , McLendon Roger E. , Marasco Wayne A. , Zalutsky Michael R. , Bigner Darell D. 
Published: November 2009

AbstractMultidrug resistance protein 3 (MRP3), a multidrug resistance protein identified by serial analysis of gene expression as a glioblastoma multiforme (GBM)‐associated molecule, is highly expressed in GBM, but not in normal brain cells. Thus, MRP3 is a candidate for GBM immunotargeting, but to date, no monoclonal antibody has been isolated that can target an extracellular MRP3 epitope. By phage display, we have isolated 3 recombinant, fully human, single‐chain Fv (scFv) antibodies, M25, M58 and M89, which specifically react with the extracellular N‐terminus of human MRP3. In ELISA, these scFvs reacted only with the peptide used for screening and not with other MRP3‐derived peptides. Flow cytometric analysis revealed that these scFv fragments bind specifically to viable human GBM cells displaying different MRP3 expression levels, but not to MRP3‐null cells. Furthermore, these scFv antibodies failed to react with tumor cells overexpressing other MRP proteins, including MRP1, MRP2, MRP4 and MRP5. M25 and M58 also bound to viable neurospheres. Iodogen‐labeled scFvs demonstrated a yield of 56–76%. The immunoreactive fractions of the radiolabeled M25, M58 and M89 scFvs were 32, 52 and 69%, respectively. M25 exhibited 20% internalization into D2159MG neurospheres, M58, 33% into D54MG cells and M89, 26% into D247MG. Immunohistochemical evaluation of human gliomas to determine the localization of MRP3 antigen using scFvs M25 and M58 showed a dense cytoplasmic and membranous staining pattern. These Fv‐based recombinant antibodies, which possess superior tumor penetration capabilities and selectively target tumor cells that express MRP3, may potentially be used in immunotherapy and diagnosis for brain tumors and other cancers.
Parametric and non‐parametric approaches to exits from fixed exchange rate regimes
Authors: Aşıcı Ahmet Atıl 
Published: November 2009

AbstractFollowing the demise of the Bretton‐Woods, increasing number of countries has been opting for flexible exchange rate regimes. Exiting from fixed regimes however is not without costs. Regime transitions have often been occurred in the midst of a crisis, which has considerable economic costs in terms of output contraction and exchange rate depreciation. Given the big number of countries having still fixed regimes and financial markets that are fairly close and expected to be liberalized sooner or later, issue of exiting a peg without incurring crisis is a real challenge confronting these countries. The aim of this paper is to determine the conditions under which orderly exit is possible. The paper employs Binary Recursive Tree and standard regression frameworks. Analysis shows that countries with higher output gap and overvalued real exchange rate, among others, are doomed to exit in a disorderly way. Following their exit, output collapses and exchange rate depreciates considerably. The ill‐managed financial liberalization and macroeconomic stabilization programs seem to lay the seeds of instability. An interesting finding is that the conventional strengths of parametric regression analysis can be dramatically improved by utilizing findings of non‐parametric BRT technology. Sample contains all countries depending on the data availability, and covers 1975–2004 period. Copyright © 2009 John Wiley & Sons, Ltd.
A comparative analysis of the evolution of a taxonomy for best practices: a case for ‘knowledge efficiency’
Authors: O'Leary Daniel E. 
Published: November 2009

AbstractTaxonomies play an increasingly important role in knowledge management of business best practices, providing a basis by which to index, find and communicate knowledge. However, knowledge continues to evolve over time. As a result, taxonomies must also continue to evolve as organizations innovate and change.Reportedly, firms customize best‐practice taxonomies to meet their unique organization needs. Accordingly, we might expect organizations to generate dissimilar best‐practice taxonomies. However, taxonomies must also reflect the state of knowledge in the area being categorized, and thus are likely to be similar in many ways in different organizations.The purpose of this paper is to study how taxonomies change in different organizations and how they stay the same. In order to explain the parallels in organizational taxonomies, the notion of ‘knowledge artefact efficiency’ (or knowledge efficiency) is suggested to capture the concept that new knowledge is rapidly adopted by many organizations in their knowledge management systems. Copyright © 2009 John Wiley & Sons, Ltd.
The effects of extracellular nucleotides on [Ca2+]isignalling in a human‐derived renal proximal tubular cell line (HKC‐8)
Authors: Turvey Matthew R. , Wang Yanyun , Gu Yuchun 
Published: November 2009

AbstractHKC‐8 cells are a human‐derived renal proximal tubular cell line and provide a useful model system for the study of human renal cell function. In this study, we aimed to determine [Ca2+]isignalling mediated by P2 receptor in HKC‐8. Fura‐2 and a ratio imaging method were employed to measure [Ca2+]iin HKC‐8 cells. Our results showed that activation of P2Y receptors by ATP induced a rise in [Ca2+]ithat was dependent on an intracellular source of Ca2+, while prolonged activation of P2Y receptors induced a rise in [Ca2+]ithat was dependent on intra‐ and extracellular sources of Ca2+. Pharmacological and molecular data in this study suggests that TRPC4 channels mediate Ca2+entry in coupling to activation of P2Y in HKC‐8 cells. U73221, an inhibitor of PI‐PLC, did not inhibit the initial ATP‐induced response; whereas D609, an inhibitor of PC‐PLC, caused a significant decrease in the initial ATP‐induced response, suggesting that P2Y receptors are coupled to PC‐PLC. Although P2X were present in HKC‐8, The P2X agonist, α,β me‐ATP, failed to cause a rise in [Ca2+]i. However, PPADS at a concentration of 100 µM inhibits the ATP‐induced rise in [Ca2+]i. Our results indicate the presence of functional P2Y receptors in HKC‐8 cells. ATP‐induced [Ca2+]ielevation via P2Y is tightly associated with PC‐PLC and TRP channel. J. Cell. Biochem. 109: 132–139, 2010. © 2009 Wiley‐Liss, Inc.
Determinants of pluripotency: From avian, rodents, to primates
Authors: Martins‐Taylor Kristen , Xu Ren‐He 
Published: November 2009

AbstractSince mouse embryonic stem (ES) cells was first derived in 1981, the ability of this unprecedented cell type to self‐renew and differentiate without limit has revolutionized the discovery tools that are used to study gene functions and development. Furthermore, they have inspired others to hunt for similar cells from other species. The derivation of human ES cells in 1998 has accelerated these discoveries and has also widely provoked public interest, due to both the scientific significance of these cells for human tissue regeneration and the ethical disputes over the use of donated early human embryos. However, this is no longer a barrier, with the recent discovery of methods that can convert differentiated somatic cells into ES‐like cells or induced pluripotent stem (iPS) cells, by using defined reprogramming factors. This review attempts to summarize the progresses in the derivation of ES cells (as well as other embryo‐derived pluripotent cells) and iPS cells from various species. We will focus on the molecular and biological features of the cells, as well as the different determinants identified thus far to sustain their pluripotency. J. Cell. Biochem. 109: 16–25, 2010. © 2009 Wiley‐Liss, Inc.
The intermediate filament vimentin regulates chondrogenesis of adult human bone marrow‐derived multipotent progenitor cells
Authors: Bobick Brent E. , Tuan Rocky S. , Chen Faye H. 
Published: November 2009

AbstractCytoskeletal proteins play important regulatory roles in a variety of cellular processes, including proliferation, migration, and differentiation. However, whereas actin and tubulin have established roles regulating developmental chondrogenesis, there is no evidence supporting a function for the intermediate filament vimentin in embryonic cartilage formation. We hypothesized that vimentin may regulate the chondrogenic differentiation of adult multipotent progenitor cells (MPCs), such as those involved in cartilage formation during bone fracture repair. As our model of adult progenitor cell chondrogenesis, we employed high‐density pellet cultures of human bone marrow‐derived MPCs. siRNA‐mediated knockdown of vimentin mRNA and protein triggered a reduction in the extent of MPC cartilage formation, as evidenced by depressed accumulation of mRNAs for the cartilage‐specific marker genes aggrecan and collagen type II, as well as reduced levels of Alcian blue‐stainable proteoglycan and collagen II protein in the extracellular matrix. Moreover, mRNA and protein levels for the chondro‐regulatory transcription factors SOX5, SOX6, and SOX9 were diminished by vimentin knockdown. Depleted cellular vimentin also induced a drastic reduction in PKA phosphorylation levels but did not affect the phosphorylation of multiple other chondro‐regulatory kinases and transcription factors, including ERK1/2, p38, Smad2, and Smad1/5/8. Importantly, siRNA‐mediated knockdown of PKA C‐α mRNA and protein mimicked the reduction in chondrogenesis caused by diminished cellular vimentin. Finally, overexpression of vimentin in MPCs significantly enhanced the activity of a transfected collagen II promoter‐luciferase reporter gene. In conclusion, we describe a novel role for the intermediate filament vimentin as a positive regulator of adult human bone marrow‐derived MPC chondrogenesis. J. Cell. Biochem. 109: 265–276, 2010. Published 2009 Wiley‐Liss, Inc.
Ceramide plays a prominent role in MDA‐7/IL‐24‐induced cancer‐specific apoptosis
Authors: Sauane Moira , Su Zao‐zhong , Dash Rupesh , Liu Xiang , Norris James S. , Sarkar Devanand , Lee Seok‐Geun , Allegood Jeremy C. , Dent Paul , Spiegel Sarah , Fisher Paul B. 
Published: November 2009

AbstractMelanoma differentiation associated gene‐7/interleukin‐24 (mda‐7/IL‐24) uniquely displays broad cancer‐specific apoptosis‐inducing activity through induction of endoplasmic reticulum (ER) stress. We hypothesize that ceramide, a promoter of apoptosis, might contribute to mda‐7/IL‐24 induction of apoptosis. Ad.mda‐7‐infected tumor cells, but not normal cells, showed increased ceramide accumulation. Infection with Ad.mda‐7 induced a marked increase in various ceramides (C16, C24, C24:1) selectively in prostate cancer cells. Inhibiting the enzyme serine palmitoyltransferase (SPT) using the potent SPT inhibitor myriocin (ISP1), impaired mda‐7/IL‐24‐induced apoptosis and ceramide production, suggesting that ceramide formation caused by Ad.mda‐7 occurs through de novo synthesis of ceramide and that ceramide is required for mda‐7/IL‐24‐induced cell death. Fumonisin B1 (FB1) elevated ceramide formation as well as apoptosis induced by Ad.mda‐7, suggesting that ceramide formation may also occur through the salvage pathway. Additionally, Ad.mda‐7 infection enhanced expression of acid sphingomyelinase (ASMase) with a concomitant increase in ASMase activity and decreased sphingomyelin in cancer cells. ASMase silencing by RNA interference inhibited the decreased cell viability and ceramide formation after Ad.mda‐7 infection. Ad.mda‐7 activated protein phosphatase 2A (PP2A) and promoted dephosphorylation of the anti‐apoptotic molecule BCL‐2, a downstream ceramide‐mediated pathway of mda‐7/IL‐24 action. Pretreatment of cells with FB1 or ISP‐1 abolished the induction of ER stress markers (BiP/GRP78, GADD153 and pospho‐eIF2α) triggered by Ad.mda‐7 infection indicating that ceramide mediates ER stress induction by Ad.mda‐7. Additionally, recombinant MDA‐7/IL‐24 protein induced cancer‐specific production of ceramide. These studies define ceramide as a key mediator of an ER stress pathway that may underlie mda‐7/IL‐24 induction of cancer‐specific killing. J. Cell. Physiol. 222: 546–555, 2010. © 2009 Wiley‐Liss, Inc.
2‐methoxyestradiol inhibits atorvastatin‐induced rounding of human vascular smooth muscle cells
Authors: Yin Hao , Gui Yu , Zheng Xi‐Long 
Published: November 2009

AbstractThe cardiovascular benefits of statins, including atorvastatin (ATV), have been reported to be gender‐dependent, but the underlying mechanism is unclear. In this study we examine whether estrogen and its metabolite, 2‐methoxyestradiol (2ME), affect the rounding response of human vascular smooth muscle cells (SMCs) induced by ATV. Twenty‐four hour treatment with ATV (10–100 µM) induced rounding of cultured human SMCs. Addition of 2ME (1–20 µM), but not 17β‐estradiol, for 2 h induced re‐spreading of rounded cells. Our further studies showed that the effects of 2ME were mimicked by microtubule‐disrupting drugs and inhibited by taxol. Inhibition of RhoA and ROCK (Rho‐kinase) by C3‐toxin and H‐1152, respectively, blocked 2ME effects. 2ME effects were also blocked by treatment with either actin‐interfering drugs, such as cytochalasin D and jasplakinolide, or myosin inhibitor blebbistatin. ML‐7 and ‐9, the inhibitors for myosin light chain kinase, inhibited 2ME effect as well. ATV treatment induced a decrease of F‐actin content and Thr18/Ser19 dual phosphorylation of myosin regulatory light chain (MRLC), which was rescued by 2ME or mevalonate. The rescue effects of 2ME on F‐actin content and MRLC dual phosphorylation were abolished by taxol or H‐1152. In addition, kinesin Eg5 inhibitor monastrol and dynein inhibitor erythro‐9‐3‐(2‐hydroxynonyl) adenine (EHNA) significantly blocked 2ME effects. Finally, our results revealed that 2ME inhibited the migration of SMCs induced by ATV (0.1 µM) in wound healing assay and Boyden chamber assay. In summary, our data show that 2ME, but not estrogen, inhibits ATV‐induced rounding of human SMCs through induction of microtubule disassembly and activation of the Rho‐ROCK‐actinomyosin pathway. J. Cell. Physiol. 222: 556–564, 2010. © 2009 Wiley‐Liss, Inc.
7‐ketocholesterol and 5,6‐secosterol modulate differently the stress‐activated mitogen‐activated protein kinases (MAPKs) in liver cells
Authors: Anticoli Simona , Arciello Mario , Mancinetti Adriano , De Martinis Massimo , Ginaldi Lia , Iuliano Luigi , Balsano Clara 
Published: November 2009

AbstractEnhanced oxidative stress is a common feature of liver diseases and contributes to chronic liver disease (CLD) progression by inducing fibrogenesis during liver regeneration. Peroxidation products of cholesterol metabolism, named oxysterols, are new and reliable markers of oxidative stress in vivo. Patients affected by CLDs present high plasma levels of oxysterols, raising the question of the origin and biological relevance of these compounds in the pathophysiology of chronic liver damage. The aim of this study was to examine the molecular basis of the biological effects of oxysterols on liver‐derived cells, HepG2 and Huh7. Cells were treated with different concentrations (10−9 to 10−5 M) of 7‐ketocholesterol used as a reference, and 5,6‐secosterol, a recently discovered oxysterol. FACS investigations, caspase‐3 activation, and Sytox Green immunofluorescent assay showed that pathological concentrations of oxysterols induced necrosis (30–50%) after 48 h of treatment. The two analyzed compounds displayed a similar, but not identical, behavior. In fact, 5,6‐secosterol, but not 7‐ketocholesterol, induced cell senescence. Notably, low concentrations of 5,6‐secosterol caused a sustained activation of ERK1/2, inducing cell proliferation, this unexpected behavior should be better characterized by further studies. Since enhanced oxidative stress is known to worsen liver chronic hepatitis and frequently results in overall decreased cellular survival, our data suggest the important and different role oxysterols may have in interfering with physiological liver tissue regeneration in injured human liver. Antioxidant treatment may provide a highly specific and effective mean to counteract the common consequences of oxidative stress on chronic hepatitis, such as fibrosis/cirrhosis and liver failure. J. Cell. Physiol. 222: 586–595, 2010. © 2009 Wiley‐Liss, Inc.