bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rlip76 transports sunitinib and sorafenib and mediates drug resistance in kidney cancer
Authors: Singhal Sharad S. , Sehrawat Archana , Sahu Mukesh , Singhal Preeti , Vatsyayan Rit , Rao Lelsani Poorna Chandra , Yadav Sushma , Awasthi Sanjay 
Published: July 2009

AbstractRLIP76 is a stress‐responsive membrane protein implicated in the regulation of multiple cellular signaling pathways. It represents the predominant glutathione‐conjugate (GS‐E) transporter in cells. We have shown that RLIP76 plays a crucial role in defending cancer cells from radiation and chemotherapeutic toxin‐mediated apoptosis, and that its inhibition by antibodies or depletion by siRNA or antisense causes apoptosis in a number of cancer cell types. We demonstrated for the first time that the striking anti‐neoplastic effects with no evident toxicity in terms of either weight loss or metabolic effects are also demonstrable for the antibody, antisense and siRNA in a renal cell xenografts model of Caki‐2 cells (Singhal et al., Cancer Res., 2009, 69: 4244). Present studies were performed to determine if RLIP76 targeting is more broadly applicable in other kidney cancer cell lines, to compare the signaling effects of RLIP76 antisense with kinase inhibitors used in treatment of renal cell carcinoma, and to determine whether kinase inhibitors were substrates for transport by RLIP76. Results of these studies show that sorafenib as well as sunitinib are substrates for transport by RLIP76 thus are competitive inhibitors of GS‐E transport. Furthermore, kinase inhibition in the ERK as well as PI3K pathways by RLIP76 depletion is more profound and consistent and is more widely apparent in a number of renal carcinoma cell lines. These studies offer strong support for our overall hypothesis that RLIP76 is an overarching anti‐apoptosis mechanism that, if inhibited, can be more broadly effective in the treatment of renal cell carcinoma.
Outcome prediction and risk assessment by quantitative pyrosequencing methylation analysis of the SFN gene in advanced stage, high‐risk, neuroblastic tumor patients
Authors: Banelli Barbara , Bonassi Stefano , Casciano Ida , Mazzocco Katia , Di Vinci Angela , Scaruffi Paola , Brigati Claudio , Allemanni Giorgio , Borzì Luana , Tonini Gian Paolo , Romani Massimo 
Published: July 2009

AbstractThe aim of our study was to identify threshold levels of DNA methylation predictive of the outcome to better define the risk group of stage 4 neuroblastic tumor patients. Quantitative pyrosequencing analysis was applied to a training set of 50 stage 4, high risk patients and to a validation cohort of 72 consecutive patients. Stage 4 patients at lower risk and ganglioneuroma patients were included as control groups. Predictive thresholds of methylation were identified by ROC curve analysis. The prognostic end points of the study were the overall and progression‐free survival at 60 months. Data were analyzed with the Cox proportional hazard model. In a multivariate model the methylation threshold identified for the SFN gene (14.3.3σ) distinguished the patients presenting favorable outcome from those with progressing disease, independently from all known predictors (Training set: Overall Survival HR 8.53, p = 0.001; Validation set: HR 4.07, p = 0.008). The level of methylation in the tumors of high‐risk patients surviving more than 60 months was comparable to that of tumors derived from lower risk patients and to that of benign ganglioneuroma. Methylation above the threshold level was associated with reduced SFN expression in comparison with samples below the threshold. Quantitative methylation is a promising tool to predict survival in neuroblastic tumor patients. Our results lead to the hypothesis that a subset of patients considered at high risk—but displaying low levels of methylation—could be assigned at a lower risk group.
Role of ERCC1 promoter hypermethylation in drug resistance to cisplatin in human gliomas
Authors: Chen Hua‐Yun , Shao Cui‐Jie , Chen Fu‐Rong , Kwan Aij‐Lie , Chen Zhong‐Ping 
Published: July 2009

AbstractOverexpression of ERCC1 mRNA is associated with drug resistance to cisplatin in human gliomas, but the role of the ERCC1 promoter in drug resistance has not been demonstrated. We have used sodium bisulfite sequencing to compare ERCC1 promoter methylation patterns in cisplatin‐sensitive and cisplatin‐resistant glioma cells. The levels of ERCC1 DNA methylation, mRNA and protein in 32 human glioma samples were examined by methylation specific PCR, real‐time RT‐PCR and immunohistochemistry, respectively. Meanwhile, cisplatin sensitivities to these human glioma samples were tested by histoculture drug response assay. Hypermethylation was observed in the upstream 5Kb region of the ERCC1 promoter of cisplatin‐sensitive glioma cell lines. ERCC1 DNA methylation levels were highly variable in 32 human glioma samples ranging from 0.1 to 0.87, which have shown significant difference between cisplatin‐sensitive samples and cisplatin‐resistant samples (p < 0.05). The relative expression levels of ERCC1 mRNA in 32 glioma samples were also variable from 0.01 to 5.71. No detectable or low expression of ERCC1 protein was shown in 7 glioma samples. ERCC1 promoter methylation was inversely correlated to mRNA expression (r = −0.903 p = 0.001) as well as protein expression (r = −0.884 p = 0.001). Moreover, ERCC1 mRNA expression was significantly associated with protein levels (r = 0.840 p = 0.001). In summary, the aberrant CpG island methylation in ERCC1 promoter region exists in human glioma cell lines as well as clinical glioma samples. ERCC1 DNA methylation could regulate the expression of downstream mRNA and protein, and was associated with cisplatin chemosensitivity.
Energy dispersive X‐ray analysis of titanium dioxide nanoparticle distribution after intravenous and subcutaneous injection in mice
Authors: Patri Anil , Umbreit Thomas , Zheng J. , Nagashima K. , Goering Peter , Francke‐Carroll Sabine , Gordon Edward , Weaver James , Miller Terry , Sadrieh Nakissa , McNeil Scott , Stratmeyer Mel 
Published: July 2009

AbstractIn an effort to understand the disposition and toxicokinetics of nanoscale materials, we used EDS (energy dispersive X‐ray spectroscopy) to detect and map the distribution of titanium dioxide (TiO2) in tissue sections from mice following either subcutaneous (s.c.) or intravenous (i.v.) injection. TiO2 nanoparticles were administered at a dose of 560 mg/kg (i.v.) or 5600 mg/kg (s.c.) to Balb/c female mice on two consecutive days. Tissues (liver, kidney, lung, heart, spleen, and brain) were examined by light microscopy, TEM (transmission electron microscopy), SEM (scanning electron microscopy), and EDS following necropsy one day after treatment. Particle agglomerates were detected by light microsopy in all tissues examined, EDS microanalysis was used to confirm that these tissues contained elemental titanium and oxygen. The TEM micrographs and EDS spectra of the aggregates were compared with in vitro measurements of TiO2 nanoparticle injection solution (i.e., in water). The nanoparticles were also characterized using dynamic light scattering in water, 10 mM NaCl, and phosphate buffered saline (PBS). In low ionic strength solvents (water and 10 mM NaCl), the TiO2 particles had average hydrodynamic diameters ranging from 114–122 nm. In PBS, however, the average diameter increases to 1–2 μm, likely due to aggregation analogous to that observed in tissue by TEM and EDS. This investigation demonstrates the suitability of energy dispersive X‐ray spectroscopy (EDS) for detection of nanoparticle aggregates in tissues and shows that disposition of TiO2 nanoparticles depends on the route of administration (i.v. or s.c.). Published in 2009 by John Wiley and Sons, Ltd.
Analyzing cell fate control by cytokines through continuous single cell biochemistry
Authors: Rieger Michael A. , Schroeder Timm 
Published: July 2009

AbstractCytokines are important regulators of cell fates with high clinical and commercial relevance. However, despite decades of intense academic and industrial research, it proved surprisingly difficult to describe the biological functions of cytokines in a precise and comprehensive manner. The exact analysis of cytokine biology is complicated by the fact that individual cytokines control many different cell fates and activate a multitude of intracellular signaling pathways. Moreover, although activating different molecular programs, different cytokines can be redundant in their biological effects. In addition, cytokines with different biological effects can activate overlapping signaling pathways. This prospect article will outline the necessity of continuous single cell biochemistry to unravel the biological functions of molecular cytokine signaling. It focuses on potentials and limitations of recent technical developments in fluorescent time‐lapse imaging and single cell tracking allowing constant long‐term observation of molecules and behavior of single cells. J. Cell. Biochem. 108: 343–352, 2009. © 2009 Wiley‐Liss, Inc.
Distribution of TGF‐β isoforms and signaling intermediates in corneal fibrotic wound repair
Authors: Huh Man‐IL , Kim Yeoun‐Hee , Park Jong‐Hyuck , Bae Sung‐Won , Kim Min‐Hee , Chang Yongmin , Kim Song‐Ja , Lee Sun‐Ryung , Lee Young‐Sup , Jin Eun‐Jung , Sonn Jong‐Kyung , Kang Shin‐Sung , Jung Jae‐Chang 
Published: July 2009

AbstractIn this study, temporal and spatial distribution of three TGF‐β isoforms and their downstream signaling pathways including pSmad2 and p38MAPK were examined during fibrotic wound repair. In normal chick corneas, TGF‐β1, ‐2, and ‐3 were weakly detected in Bowman's layer (BL). In healing corneas, TGF‐β1 was primarily deposited in the fibrin clot and the unwounded BL. TGF‐β2 was highly expressed in healing epithelial and endothelial cells, and numerous active fibroblasts/myofibroblasts. TGF‐β3 was mainly detected in the unwound region of basal epithelial cells. α‐Smooth muscle actin (α‐SMA) was initially appeared in the posterior region of repairing stroma at day 3, and was detected in the entire healing stroma by day 7. Notably, α‐SMA was absent in the central region of healing stroma by day 14, and its staining pattern was similar to those of TGF‐β2 and p38MAPK. By contrast, pSmad2 was mainly detected in the fibroblasts. In normal cornea, laminin was mainly detected in both epithelial basement membrane (BM) and Descemet's membrane (DM). By contrast to reconstitution of the BM in the wound region, the DM was not repaired although endothelial layer was regenerated, indicating that high levels of TGF‐β2 were released into the posterior region of healing stroma on day 14. High levels of α‐SMA staining, shown in cultured repair stromal cells from healing corneas on day 14 and in TGF‐β2 treated normal stromal cells, were significantly reduced by p38MAPK inhibition. Collectively, this study suggests that TGF‐β2‐mediated myofibroblast transformation is mediated, at least partly, by the p38MAPK pathway in vivo. J. Cell. Biochem. 108: 476–488, 2009. © 2009 Wiley‐Liss, Inc.
Glucosamine inhibits IL‐1β‐mediated IL‐8 production in prostate cancer cells by MAPK attenuation
Authors: Tsai Cheng‐Yen , Lee Tzong‐Shyuan , Kou Yu Ru , Wu Yuh‐Lin 
Published: July 2009

AbstractInflammation is a complex process involving cytokine production to regulate host defense cascades. In contrast to the therapeutic significance of acute inflammation, a pathogenic impact of chronic inflammation on cancer development has been proposed. Upregulation of inflammatory cytokines, such as IL‐1β and IL‐8, has been noted in prostate cancer patients and IL‐8 has been shown to promote prostate cancer cell proliferation and migration; however, it is not clear whether IL‐1β regulates IL‐8 expression in prostate cancer cells. Glucosamine is widely regarded as an anti‐inflammatory agent and thus we hypothesized that if IL‐1β activated IL‐8 production in prostate cancer cells, then glucosamine ought to blunt such an effect. Three prostate cancer cell lines, DU‐145, PC‐3, and LNCaP, were used to evaluate the effects of IL‐1β and glucosamine on IL‐8 expression using ELISA and RT‐PCR analyses. IL‐1β elevated IL‐8 mRNA expression and subsequent IL‐8 secretion. Glucosamine significantly inhibited IL‐1β‐induced IL‐8 secretion. IL‐8 appeared to induce LNCaP cell proliferation by MTT assay; involvement of IL‐8 in IL‐1β‐dependent PC‐3 cell migration was demonstrated by wound‐healing and transwell migration assays. Inhibitors of MAPKs and NFκB were used to pinpoint MAPKs but not NFκB being involved in IL‐1β‐mediated IL‐8 production. IL‐1β‐provoked phosphorylation of all MAPKs was notably suppressed by glucosamine. We suggest that IL‐1β can activate the MAPK pathways resulting in an induction of IL‐8 production, which promotes prostate cancer cell proliferation and migration. In this context, glucosamine appears to inhibit IL‐1β‐mediated activation of MAPKs and therefore reduces IL‐8 production; this, in turn, attenuates cell proliferation/migration. J. Cell. Biochem. 108: 489–498, 2009. © 2009 Wiley‐Liss, Inc.
Involvement of STIM1 in the proteinase‐activated receptor 1‐mediated Ca2+influx in vascular endothelial cells
Authors: Hirano Katsuya , Hirano Mayumi , Hanada Akiko 
Published: July 2009

AbstractThrombin increases the cytosolic Ca2+concentrations and induces NO production by activating proteinase‐activated receptor 1 (PAR1) in vascular endothelial cells. The store‐operated Ca2+influx is a major Ca2+influx pathway in non‐excitable cells including endothelial cells and it has been reported to play a role in the thrombin‐induced Ca2+signaling in endothelial cells. Recent studies have identified stromal interaction molecule 1 (STIM1) to function as a sensor of the store site Ca2+content, thereby regulating the store‐operated Ca2+influx. However, the functional role of STIM1 in the thrombin‐induced Ca2+influx and NO production in endothelial cells still remains to be elucidated. Fura‐2 and diaminorhodamine‐4M fluorometry was utilized to evaluate the thrombin‐induced changes in cytosolic Ca2+concentrations and NO production, respectively, in porcine aortic endothelial cells transfected with small interfering RNA (siRNA) targeted to STIM1. STIM1‐targeted siRNA suppressed the STIM1 expression and the thapsigargin‐induced Ca2+influx. The degree of suppression of the STIM1 expression correlated well to the degree of suppression of the Ca2+influx. The knockdown of STIM1 was associated with a substantial inhibition of the Ca2+influx and a partial reduction of the NO production induced by thrombin. The thrombin‐induced Ca2+influx exhibited the similar sensitivity toward the Ca2+influx inhibitors to that seen with the thapsigargin‐induced Ca2+influx. The present study provides the first evidence that STIM1 plays a critical role in the PAR1‐mediated Ca2+influx and Ca2+‐dependent component of the NO production in endothelial cells. J. Cell. Biochem. 108: 499–507, 2009. © 2009 Wiley‐Liss, Inc.
Negative regulation of endogenous protein kinase Cα on the dynamic change of carbachol‐induced intracellular calcium response in different melanoma cells
Authors: Wang Huan , Yu Yao‐Qing , Liao Wen‐Jun , Wang Zong‐Ren , Lv Ya‐Jie , Zhang Yan‐Guo , Gao Tian‐Wen 
Published: July 2009

AbstractRegulations of intracellular protein kinase C (PKC) on carbachol (CCh)‐induced intracellular calcium ([Ca2+]i) responses were investigated in different stages of melanoma cells. We found that CCh (1 mM) significantly increased [Ca2+]i with 6‐, 4‐, 4‐, and 25‐folds intensities in WM793B, 451Lu, SK‐MEL‐5, and A2058 melanoma cells, respectively. Pretreatment of phorbol 12, 13‐dibutyrate (PDBu, 2 µM), an activator of intracellular PKC, significantly suppressed CCh‐induced peak reactions in WM793B, SK‐MEL‐5, and A2058 cells. RT‐PCR data showed that mRNA levels of PKCα were 12‐, 4‐, 6‐, and 0.9‐folds higher in above four melanoma cells. Short interfering RNA (siRNA) targeting to PKCα in WM793B cells enhanced CCh‐induced peak calcium reactions. Present data indicated that CCh‐induced [Ca2+]i responses were dynamically changed in different stages of melanoma progression. Moreover, intracellular PKCα activated by exogenous agonist and expressed through endogenous gene transcription negatively regulated CCh‐induced calcium responses. The functional analysis on the relationship between CCh‐induced calcium response and endogenous PKCα expression might be helpful to predict the development of melanoma. J. Cell. Physiol. 221: 276–282, 2009. © 2009 Wiley‐Liss, Inc.
Regulation of HIV‐1 transcription at 3% versus 21% oxygen concentration
Authors: Charles Sharroya , Ammosova Tatyana , Cardenas Jessica , Foster Altreisha , Rotimi Jamie , Jerebtsova Marina , Ayodeji Abisola A. , Niu Xiaomei , Ray Patricio E. , Gordeuk Victor R. , Kashanchi Fatah , Nekhai Sergei 
Published: July 2009

AbstractHIV transcription is induced by the HIV‐1 Tat protein, in concert with cellular co‐factors including CDK9, CDK2, NF‐κB, and others. The cells of most of the body's organs are exposed to ∼3–6% oxygen, but most in vitro studies of HIV replication are conducted at 21% oxygen. We hypothesized that activities of host cell factors involved in HIV‐1 replication may differ at 3% versus 21% O2, and that such differences may affect HIV‐1 replication. Here we show that Tat‐induced HIV‐1 transcription was reduced at 3% O2 compared to 21% O2. HIV‐1 replication was also reduced in acutely or chronically infected cells cultured at 3% O2 compared to 21% O2. This reduction was not due the decreased cell growth or increased cellular toxicity and also not due to the induction of hypoxic response. At 3% O2, the activity of CDK9/cyclin T1 was inhibited and Sp1 activity was reduced, whereas the activity of other host cell factors such as CDK2 or NF‐κB was not affected. CDK9‐specific inhibitor ARC was much less efficient at 3% compared to 21% O2 and also expression of CDK9/cyclin T1‐dependent IκB inhibitor α was repressed. Our results suggest that lower HIV‐1 transcription at 3% O2 compared to 21% O2 may be mediated by lower activity of CDK9/cyclin T1 and Sp1 at 3% O2 and that additional host cell factors such as CDK2 and NF‐κB might be major regulators of HIV‐1 transcription at low O2 concentrations. J. Cell. Physiol. 221: 469–479, 2009. © 2009 Wiley‐Liss, Inc.
293 cells over‐expressing human ADI1 and CD81 are permissive for serum‐derived hepatitis C virus infection
Authors: Cheng Ju‐Chien , Yeh Yung‐Ju , Pai Li‐Mei , Chang Ming‐Ling , Yeh Chau‐Ting 
Published: July 2009

AbstractHuman aci‐reductone dioxygenase 1 (ADI1) is a member of the Cupin superfamily. It binds to and inhibits the activities of membrane‐type 1 matrix metalloproteinase, a protein known to interact with the tight junction protein, claudin‐1. Previously, a variant protein, named submergence‐induced protein‐like factor (Sip‐L), consisting of ADI1 amino acids 64–179, was found to support hepatitis C virus (HCV) infection and replication in 293 cells. In the present study, it was discovered that over‐expression of human ADI1 in 293 cells (293‐ADI1 cells) also supported HCV infection and replication. Using serum‐derived HCV as an infectious source, enhanced cell uptake of HCV to a Northern blot detectable level was found in 293 cells over‐expressing both CD81 and ADI1 (293‐ADI1‐CD81 cells). The enhanced cell entry was confirmed by the use of the vesicular stomatitis virus‐based HCV pseudotype particles. However, transfection of HCV replicon RNA by electroporation into naïve 293 and 293‐ADI1 cells revealed no difference in replication efficiency. Using the infectious J6/JFH chimera as an infectious source, the infectivity was compared between 293‐ADI1‐CD81 and Huh‐7.5 cells. More infection foci were formed in the 293‐ADI1‐CD81 cells in the first round of infection. In conclusion, human ADI1 over‐expression in 293 cells enhances cell entry but not replication of HCV. 293‐ADI1‐CD81 cells are permissive for serum‐derived HCV infection. J. Med. Virol. 81:1560–1568, 2009. © 2009 Wiley‐Liss, Inc.
A serological and molecular survey of hepatitis B in children 15 years after inception of the national hepatitis B vaccination program in eastern China
Authors: Dong Ying , Liu She‐Lan , Zhai Xiang‐Jun , Zhu Feng‐Cai , Pan Hao , Yu Jia‐xi , Chen Yin‐zhong , Xie Yi‐Rui , Zhang Xiao‐Yu , Zhang Hong‐Mei , Li Lan‐Juan , Wang Hua , Ruan Bing 
Published: July 2009

AbstractThe emergence of mutations in the hepatitis B virus (HBV) S gene has threatened the long‐term success of vaccination programs since the worldwide introduction of effective vaccines against hepatitis B. This study was conducted on 5,407 children (0–8 years old) in eastern China in 2007. We analyzed the prevalence of HBsAg, anti‐HBs, and “a”‐determinant mutations in the HBV S gene by microparticle enzyme immunoassays, PCR, and DNASTAR software. The total HBsAg prevalence was 1.52% (82/5,407) in the children and increased with age. In contrast, the positive rate (65.42%, 2,374/3,629) and the titers of anti‐HBs decreased with age. The predominant infection was HBV of genotype C and serotype adr (45/51; 88% of cases). Mutations of I126T, amino acid 137 (nt553T deletion mutation), G145A, G145R, and F158S were found in the children; the mutations of amino acid 137 and F158S have not been reported previously. The total prevalence of mutant strains was 14% (7/51). To investigate whether the infection resulted from maternal transmission, we compared the S gene sequences in 16 mother–child pairs. Fourteen mother–child pairs exhibited the same HBV genotype, with 99.5–100% sequence homology in the S gene, while two pairs exhibited different genotypes. This study suggested that the hepatitis B vaccination strategies in eastern China have been successful. Although the emergence of “a”‐determinant mutations in the HBV S gene have resulted in HBV infection in immunized children, this does not pose a threat to the vaccination strategies. The HBV‐infected children had contracted the infection via vertical transmission. J. Med. Virol. 81:1517–1524, 2009. © 2009 Wiley‐Liss, Inc.
Three cases of paralytic poliomyelitis associated with type 3 vaccine poliovirus strains in Bulgaria
Authors: Korsun Neli , Kojouharova Mira , Vladimirova Nadezhda , Fiore Lucia , Litvinenko Ivan , Buttinelli Gabriele , Fiore Stefano , Voynova‐Georgieva Violeta , Mladenova Zornitsa , Georgieva Daniela 
Published: July 2009

AbstractOral poliovirus vaccine (OPV) can cause, in extremely rare cases vaccine‐associated paralytic poliomyelitis in recipients, or contacts of vaccinees. Three cases of vaccine‐associated paralytic poliomyelitis (two contacts and one recipient) occurred in the Bourgas region of Bulgaria in the spring of 2006. The first two cases, notified as acute flaccid paralysis, were 55 days old unvaccinated twin brothers, having been in contact with vaccinees. The third case concerned a 4‐month‐old infant who had received the first OPV dose 37 days prior to the onset of illness. Complete clinical, epidemiological, virological, serological and molecular investigations of the children with paralysis and their contacts were undertaken. In all the three cases type 3 polioviruses were isolated from fecal samples and characterized as Sabin‐like poliovirus strains. Type 3 polioviruses isolated from the twin brothers demonstrated by sequence analysis U‐to‐C back mutation at nt 472 of the 5′ UTR, known to correlate with neurovirulence, and mutation in the VP1 region. Type 3 poliovirus isolated from the third child demonstrated in the 3D sequenced region a recombination with Sabin type 1 poliovirus. In the latter region, three silent mutations and one, resulting in amino acid substitution, were also observed. The clinical, epidemiological and virological data and the neurological sequelae observed 60 days following the onset of paralysis, confirmed the diagnosis of vaccine‐associated paralytic poliomyelitis in all the three patients. J. Med. Virol. 81:1661–1667, 2009. © 2009 Wiley‐Liss, Inc.