bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic variations of DNA repair genes and their prognostic significance in patients with acute myeloid leukemia
Authors: Shi Jing‐Yi , Ren Zhi‐Hong , Jiao Bo , Xiao Run , Yun Hai‐Yang , Chen Bing , Zhao Wei‐Li , Zhu Qi , Chen Zhu , Chen Sai‐Juan 
Published: March 2010

AbstractCommon genetic variations in genes involved in DNA repair or response to genotoxic stress may influence both cancer susceptibility and treatment response individually or interactively. However, in acute myeloid leukemia (AML), the relevance of these genetic variations remains to be fully established. In this study, we analyzed 42 genetic variations among 15 candidate genes in 307 AML patients and 560 age‐sex matched controls. Their associations with chemotherapy response were further evaluated in combination with other well‐established prognostic factors. An increased risk of AML was found in individuals heterozygous for XPD 2251A>C (rs13181) with an odds ratio (OR) of 1.637 (95% confidence interval [CI]: 1.118–2.395), and the increased risk could be attributed to C allele (OR = 1.505, 95% CI: 1.061–2.134). Postchemotherapy response analysis revealed that AML patients heterozygous for ATM 4138C>T (rs3092856) or GG homozygous for TP53 215C>G (rs1042522) were independently linked to inferior treatment outcomes. These results uncover novel prognostic factors for AML patients treated with chemotherapy and may also indicate an etiological role of XPD in this disease.
Coinfection of hepatitis B and C viruses and risk of hepatocellular carcinoma: Systematic review and meta‐analysis
Authors: Cho Lisa Y. , Yang Jae Jeong , Ko Kwang‐Pil , Park Boyoung , Shin Aesun , Lim Min Kyung , Oh Jin‐Kyoung , Park Sohee , Kim Yoon Jun , Shin Hai‐Rim , Yoo Keun‐Young , Park Sue K. 
Published: March 2010

AbstractA subadditive effect of hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection is possible because superinfection of one virus tends to inhibit infection of the other virus. However, studies have reported inconsistent findings, and two meta‐analyses of studies from various countries (1998) and China (2005) reported a supraadditive effect for hepatocellular carcinoma (HCC) risk. Thus, we reevaluate HBV/HCV monoinfection and coinfection. Of 411 reports, we included 59 studies that assessed the association between HBV/HCV monoinfection and coinfection for HCC risk. HCC risk because of high/detectable HBV DNA and HBeAg infection was higher than HBsAg infection, whereas anti‐HCV vs anti‐HCV/HCV RNA was not different. Geographically, HCC risk was significantly higher in nonendemic than in HBV or HCV endemic areas. Subadditive effect for HCC risk was presented in recently published studies, cohort studies and studies conducted in HBV/HCV nonendemic areas; an additive effect was presented in studies conducted in HBV endemic areas; a supraadditive effect was presented in previously published studies, case‐control studies and studies conducted in HCV endemic areas. Our results suggest HBV/HCV coinfection for HCC risk is not significantly greater than HBV/HCV monoinfection, and HCC risk due to HBV or HCV is higher in nonendemic than endemic areas. The p‐heterogeneity was significant for most analyses, except HBV(+)/HCV(+) and HBV biomarker analyses. Prevention strategies targeted toward HBV or HCV monoinfected patients are needed. In addition, tailored prevention to reduce infectivity such as HBV markers (HBeAg, HBV DNA) is needed.
Unimpeded skin carcinogenesis in K14‐HPV16 transgenic mice deficient for plasminogen activator inhibitor
Authors: Masset Anne , Maillard Catherine , Sounni Nor Eddine , Jacobs Nathalie , Bruyére Françoise , Delvenne Philippe , Tacke Marlene , Reinheckel Thomas , Foidart Jean‐Michel , Coussens Lisa M. , Noël Agnès 
Published: March 2010

AbstractAngiogenesis, extracellular matrix remodeling and cell migration are associated with cancer progression and involve at least, the plasminogen activating system and its main physiological inhibitor, the plasminogen activator inhibitor‐1 (PAI‐1). Considering the recognized importance of PAI‐1 in the regulation of tumor angiogenesis and invasion in murine models of skin tumor transplantation, we explored the functional significance of PAI‐1 during early stages of neoplastic progression in the transgenic mouse model of multistage epithelial carcinogenesis (K14‐HPV16 mice). We have studied the effect of genetic deletion of PAI‐1 on inflammation, angiogenesis, lymphangiogenesis and tumor progression. In this model, PAI‐1 deficiency neither impaired keratinocyte hyperproliferation or tumor development nor affected the infiltration of inflammatory cells and development of angiogenic or lymphangiogenic vasculature. We are reporting evidence for concomitant lymphangiogenic and angiogenic switches independent to PAI‐1 status. Taken together, these data indicate that PAI‐1 is not rate limiting for neoplastic progression and vascularization during premalignant progression, or that there is a functional redundancy between PAI‐1 and other tumor regulators, masking the effect of PAI‐1 deficiency in this long‐term model of multistage epithelial carcinogenesis.
C‐Myc is a Nrf2‐interacting protein that negatively regulates phase II genes through their electrophile responsive elements
Authors: Levy Smadar , Forman Henry Jay 
Published: March 2010

Abstractc‐Myc is a transcription factor that is implicated in many cellular processes including proliferation, apoptosis and cancers. Recently, c‐Myc was shown to be involved in regulation of glutamate cysteine ligase through E‐box sequences. This investigation examined whether c‐Myc also regulates phase II genes through interaction with the electrophile response element (EpRE). Experiments were conducted in human bronchial epithelial cells using si‐RNA to knock down c‐Myc. RT‐PCR and reporter assays were used to measure transcription and promoter activity. c‐Myc downregulated transcription and promoter activity of phase II genes. Chromatin immunoprecipitation verified binding of c‐Myc to EpRE while coimmunoprecipitation demonstrated interaction of c‐Myc with Nrf2. c‐Myc also forms a ternary complex with Nrf2 and p‐c‐Jun. Finally, c‐Myc decreased Nrf2 stability. Thus, our results suggest regulation of the EpRE/Nrf2 signaling pathway by c‐Myc through both interaction with the EpRE binding complex and increased degradation of Nrf2. © 2010 IUBMB IUBMB Life, 62(3): 237–246, 2010
Arctigenin blocks the unfolded protein response and shows therapeutic antitumor activity
Authors: Kim Ju‐Young , Hwang Ji‐Hwan , Cha Mi‐Ran , Yoon Mi‐Young , Son Eun‐Soon , Tomida Akihiro , Ko Bosung , Song Si‐Whan , Shin‐ya Kazuo , Hwang Yong‐il , Park Hae‐Ryong 
Published: March 2010

AbstractCancer cells in poorly vascularized solid tumors are constantly or intermittently exposed to stressful microenvironments, including glucose deprivation, hypoxia, and other forms of nutrient starvation. These tumor‐specific conditions, especially glucose deprivation, activate a signaling pathway called the unfolded protein response (UPR), which enhances cell survival by induction of the stress proteins. We have established a screening method to discover anticancer agents that could preferentially inhibit tumor cell viability under glucose‐deprived conditions. Here we identify arctigenin (ARC‐G) as an active compound that shows selective cytotoxicity and inhibits the UPR during glucose deprivation. Indeed, ARC‐G blocked expression of UPR target genes such as phosphorylated‐PERK, ATF4, CHOP, and GRP78, which was accompanied by enhanced phosphorylation of eIF2α during glucose deprivation. The UPR inhibition led to apoptosis involving a mitochondrial pathway by activation of caspase‐9 and ‐3. Furthermore, ARC‐G suppressed tumor growth of colon cancer HT‐29 xenografts. Our results demonstrate that ARC‐G can be served as a novel type of antitumor agent targeting the UPR in glucose‐deprived solid tumors. J. Cell. Physiol. 224:33–40, 2010 © 2010 Wiley‐Liss, Inc.
RETRACTED: Sequential loss of cell cycle checkpoint control contributes to malignant transformation of murine embryonic fibroblasts induced by 20‐methylcholanthrene
Authors: Mukherjee Sudeshna , Manna Sugata , Pal Debolina , Mukherjee Pratima , Panda Chinmay K. 
Published: March 2010

AbstractDefinitive information about the number and nature of discrete steps of tumorigenesis is enigmatic. To understand the multistep nature of carcinogenesis, an in vitro model of 20‐Methylcholanthrene‐treated primary fibroblast cells CNCI‐PM‐20, from 20‐day old Swiss mouse embryo was used. Visible neoplastic changes with distinct morphological variations along with specific chromosomal aberrations like Robertsonian metacentrics, double and single‐minute chromosomes and aneuploidy were observed from Passage‐20 onwards. The cell cycle profile showed gradual increase in G2/M population till P‐32, followed by evasion of block from P‐36 onwards. Gradual increase in expression of C‐myc, CyclinD1 and a decrease in expression of P21 was observed from P‐20 onwards. CDC25A expression was significantly increased at P‐27 and remained more or less constant in subsequent passages. Additionally, an increased P16 and P53 expression were seen at P‐20 followed by their significant down‐regulation at P‐32. An increased level of phosphorylated retinoblastoma (ppRb) was observed from P‐27, probably responsible for a compromised G1/S checkpoint. The inactivation of p21 and p16 might be due to their promoter hyper‐methylation as suggested through de‐methylation experiment by 5‐aza‐deoxycytidine at P‐42. G2/M checkpoint abrogation was marked by gradual increase in expression of CyclinB1 and Cdc20, and a significant increase of Mad2 at P‐20. Interestingly, increased expression of phospho‐ATM, ATR and phospho‐Chk1 were also seen at P‐20 followed by their down‐regulation at subsequent passages, indicating a perturbation of DNA damage response pathway at early passages. Our findings therefore dramatize the multiple genetic events that can cooperate to promote tumorigenesis. J. Cell. Physiol. 224:49–58, 2010 © 2010 Wiley‐Liss, Inc.
High glucose regulates cyclin D1/E of human mesenchymal stem cells through TGF‐β1 expression via Ca2+/PKC/MAPKs and PI3K/Akt/mTOR signal pathways
Authors: Ryu Jung Min , Lee Min Young , Yun Seung Pil , Han Ho Jae 
Published: March 2010

AbstractThe elucidation of factors that support human mesenchymal stem cells (hMSCs) growth has remained unresolved partly because of the reliance of many researchers on ill‐defined, proprietary medium formulation. Thus, we investigated the effects of high glucose (D‐glucose, 25 mM) on hMSCs proliferation. High glucose significantly increased [3H]‐thymidine incorporation and cell‐cycle regulatory protein expression levels compared with 5 mM D‐glucose or 25 mM L‐glucose. In addition, high glucose increased transforming growth factor‐β1 (TGF‐β1) mRNA and protein expression levels. High glucose‐induced cell‐cycle regulatory protein expression levels and [3H]‐thymidine incorporation, which were inhibited by TGF‐β1 siRNA transfection and TGF‐β1 neutralizing antibody treatment. High glucose‐induced phosphorylation of protein kinase C (PKC), p44/42 mitogen‐activated protein kinases (MAPKs), p38 MAPK, Akt, and mammalian target of rapamycin (mTOR) in a time‐dependent manner. Pretreatment of PKC inhibitors (staurosporine, 10−6 M; bisindolylmaleimide I, 10−6 M), LY 294002 (PI3 kinase inhibitor, 10−6 M), Akt inhibitor (10−5 M), PD 98059 (p44/42 MAPKs inhibitor, 10−5 M), SB 203580 (p38 MAPK inhibitor, 10−6 M), and rapamycin (mTOR inhibitor, 10−8 M) blocked the high glucose‐induced cellular proliferation and TGF‐β1 protein expression. In conclusion, high glucose stimulated hMSCs proliferation through TGF‐β1 expression via Ca2+/PKC/MAPKs as well as PI3K/Akt/mTOR signal pathways. J. Cell. Physiol. 224:59–70, 2010 © 2010 Wiley‐Liss, Inc.
A role for PKR in hematologic malignancies
Authors: Blalock William L. , Bavelloni Alberto , Piazzi Manuela , Faenza Irene , Cocco Lucio 
Published: March 2010

AbstractThe double‐stranded RNA‐dependent kinase PKR has been described for many years as strictly a pro‐apoptotic kinase. Recent data suggest that the main purpose of this kinase is damage control and repair following stress and, if all else fails, apoptosis. Aberrant activation of PKR has been reported in numerous neurodegenerative diseases and cancer. Although a subset of myelodysplastic syndromes (MDS) and chronic lymphocytic leukemia contain low levels of PKR expression and activity, elevated PKR activity and/or expression have been detected in a wide range of hematologic malignancies, from bone marrow failure disorders to acute leukemia. With the recent findings that cancers containing elevated PKR activity are highly sensitive to PKR inhibition, we explore the role of PKR in hematologic malignancies, signal transduction pathways affected by PKR, and how PKR may contribute to leukemic transformation. J. Cell. Physiol. 223:572–591, 2010. © 2010 Wiley‐Liss, Inc.
Hypoxia induces BMP‐2 expression via ILK, Akt, mTOR, and HIF‐1 pathways in osteoblasts
Authors: Tseng Wen‐Pei , Yang Shu‐Ning , Lai Chih‐Ho , Tang Chih‐Hsin 
Published: March 2010

AbstractIt has been shown that hypoxia stimulation regulates bone formation, maintenance, and repair. Bone morphogenetic protein (BMP) plays important roles in osteoblastic differentiation and bone formation. However, the effects of hypoxia exposure on BMP‐2 expression in cultured osteoblasts are largely unknown. Here we found that hypoxia stimulation increased mRNA and protein levels of BMP‐2 by qPCR, Western blot and ELISA assay in osteoblastic cells MG‐63, hFOB and bone marrow stromal cells M2‐10B4. Integrin‐linked kinase (ILK) inhibitor (KP‐392), Akt inhibitor (1L‐6‐hydroxymethyl‐chiro‐inositol‐2‐[(R)‐2‐O‐methyl‐3‐O‐octadecylcarbonate]) or mammalian target of rapamycin (mTOR) inhibitor (rapamycin) inhibited the potentiating action of hypoxia. Exposure to hypoxia increased the kinase activity of ILK and phosphorylation of Akt and mTOR. Furthermore, hypoxia also increased the stability and activity of HIF‐1 protein. The binding of HIF‐1α to the HRE elements after exposure to hypoxia was measured by EMSA assay. Moreover, the use of pharmacological inhibitors or genetic inhibition revealed that both ILK/Akt and mTOR signaling pathway were potentially required for hypoxia‐induced HIF‐1α activation and subsequent BMP‐2 up‐regulation. Taken together, our results provide evidence that hypoxia enhances BMP‐2 expression in osteoblasts by an HIF‐1α‐dependent mechanism involving the activation of ILK/Akt and mTOR pathways. J. Cell. Physiol. 223:810–818, 2010. © 2010 Wiley‐Liss, Inc.
Involvement of Cx43 phosphorylation in 5′‐N‐ethylcarboxamide‐induced migration and proliferation of mouse embryonic stem cells
Authors: Kim Mi Ok , Lee Yu Jin , Han Ho Jae 
Published: March 2010

AbstractDespite a lot of gap junction research, the complex connection between gap junction and cell proliferation remains an exciting area of investigation. Thus, we examined the effect of connexin 43 (Cx43) on the migration and proliferation of embryonic stem (ES) cells and its related signaling pathways following stimulation with the adenosine analogue 5′‐N‐ethylcarboxamide (NECA). NECA increased phosphorylation of Cx43 which was blocked by caffeine, a non‐selective adenosine receptor antagonist. In experiment to measure the gap junctional intercellular communication, NECA blocked transfer of Lucifer yellow to neighboring cells in a scrape loading/dye transfer (SL/DT) assay. In addition, NECA‐induced phosphorylation of phosphoinositide 3‐kinase (PI3K)/Akt, protein kinase C (PKC), mitogen‐activated protein kinases (MAPKs), and nuclear factor‐kappa B (NF‐κB) signal pathways. Inhibition of these signaling pathways reduced NECA‐induced phosphorylation of Cx43. Moreover, NECA‐treated cells demonstrated phosphorylation of Src, which was blocked by caffeine. In this experiment, a disruption of Cx43 using Cx43‐specific small interfering RNA (siRNA) also enhanced Src phosphorylation. In a further study, phosphorylations of integrin β1, focal adhesion kinase (FAK), and paxillin by NECA were restrained by caffeine as well as the Src blocker, PP2. Finally, we identified that NECA‐stimulated cell migration and expressions of cell‐cycle regulatory proteins [cyclin D1, cyclin‐dependent kinase (CDK) 4, cyclin E, and CDK2]; these increases were inhibited by caffeine, or PP2. We conclude that NECA‐stimulated Cx43 phosphorylation mediated by PI3K/Akt, PKC, MAPKs, and NF‐κB, which subsequently stimulated cell migration and proliferation through Src, integrin β1, FAK, and paxillin signal pathways. J. Cell. Physiol. 224:187–194, 2010 © 2010 Wiley‐Liss, Inc.
Regulatory factors and cell populations involved in skeletal muscle regeneration
Authors: Ten Broek Roel W. , Grefte Sander , Von den Hoff Johannes W. 
Published: March 2010

AbstractSkeletal muscle regeneration is a complex process, which is not yet completely understood. Satellite cells, the skeletal muscle stem cells, become activated after trauma, proliferate, and migrate to the site of injury. Depending on the severity of the myotrauma, activated satellite cells form new multinucleated myofibers or fuse to damaged myofibers. The specific microenvironment of the satellite cells, the niche, controls their behavior. The niche contains several components that maintain satellite cells quiescence until they are activated. In addition, a great diversity of stimulatory and inhibitory growth factors such as IGF‐1 and TGF‐β1 regulate their activity. Donor‐derived satellite cells are able to improve muscle regeneration, but their migration through the muscle tissue and across endothelial layers is limited. Less than 1% of their progeny, the myoblasts, survive the first days upon intra‐muscular injection. However, a range of other multipotent muscle‐ and non‐muscle‐derived stem cells are involved in skeletal muscle regeneration. These stem cells can occupy the satellite cell niche and show great potential for the treatment of skeletal muscle injuries and diseases. The aim of this review is to discuss the niche factors, growth factors, and other stem cells, which are involved in skeletal muscle regeneration. Knowledge about the factors regulating satellite cell activity and skeletal muscle regeneration can be used to improve the treatment of muscle injuries and diseases. J. Cell. Physiol. 224:7–16, 2010 © 2010 Wiley‐Liss, Inc.
Cadmium‐induced hormetic effect in differentiated Caco‐2 cells: ERK and p38 activation without cell proliferation stimulation
Authors: Mantha Marc , Jumarie Catherine 
Published: March 2010

AbstractCadmium (Cd) is a toxic metal that enters the food chain. Following oral ingestion, the intestinal epithelium may in part protect against Cd toxicity but is also a target tissue. Using human enterocytic‐like Caco‐2 cells, we have previously shown differences in sensitivity to Cd according to the differentiation status. The present study focuses on Cd effects on differentiated cells. Concentration and time‐dependent increases in MTT (3‐[4,5‐dimethyl‐2‐thiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide assay) activity were observed in post‐confluent cultures exclusively, with a twofold maximal stimulation in 21‐day‐old cells exposed to 10 µM Cd for 24 h. No concomitant increase in [methyl‐3H] thymidine incorporation was noted and Cd did not modify cell distribution in the cell‐cycle phases. However, Cd‐induced increase in MTT activity was inhibited by cycloheximine as well as by inhibitors of ERK1/2 and p38, but not by that of JNK. Consistently, Cd increased the levels of ERK1/2 and p38 phosphorylation. Inhibition of Ras‐GTP or PI3K enhanced the stimulatory effect of Cd, whereas mTOR inhibition had no effect. Inhibition of G protein‐phospholipase and PKC decreased MTT stimulation. These results show a hormesis‐like stimulation of Cd on MTT activity in differentiated intestinal cells exclusively. This effect is not related to cell proliferation but more likely to increased protein synthesis which involves ERK1/2 and p38 cascades and possibly PLC‐β signaling pathways. Because growth‐related differentiation of intestinal cells is linked to the selective and sequential activation of MAPKs, the impacts that these Cd‐induced perturbations in signaling pathways may have on intestinal functions clearly deserve to be investigated. J. Cell. Physiol. 224:250–261, 2010 © 2010 Wiley‐Liss, Inc.
Prolonged blockade of VEGF receptors does not damage retinal photoreceptors or ganglion cells
Authors: Miki Akiko , Miki Katsuaki , Ueno Shinji , Wersinger Delphine M. Bonnet , Berlinicke Cynthia , Shaw Gillian C. , Usui Shinichi , Wang Yuxia , Zack Donald J. , Campochiaro Peter A. 
Published: March 2010

AbstractIt has recently been reported that relatively short‐term inhibition of vascular endothelial growth factor (VEGF) signaling can cause photoreceptor cell death, a potentially clinically important finding since VEGF blockade has become an important modality of treatment of ocular neovascularization and macular edema. However, in a set of studies in which we achieved extended and complete blockage of VEGF‐induced vascular leakage through retinal expression of a VEGF binding protein, we did not observe any toxicity to retinal neurons. To follow‐up on these apparently discrepant findings, we designed a set of experiments with the kinase inhibitor SU4312, which blocks phosphorylation of VEGF receptors, to look directly for evidence of VEGF inhibition‐related retinal toxicity. Using transgenic mice with sustained expression of VEGF in photoreceptors, we determined that periocular injection of 3 µg of SU4312 every 5 days markedly suppressed subretinal neovascularization, indicating effective blockade of VEGF signaling. Wild‐type mice given periocular injections of 5 µg of SU4312 every 5 days for up to 12 weeks showed normal scotopic and photopic electroretinograms (ERGs), no TUNEL stained cells in the retina, and no reduction in outer nuclear layer thickness. Incubation of cultured ganglion cells or retinal cultures containing photoreceptors with high doses of SU4312 did not reduce cell viability. These data suggest that blocking VEGF signaling in the retina for up to 12 weeks does not damage photoreceptors nor alter ERG function and should reassure patients who are receiving frequent injections of VEGF antagonists for choroidal and retinal vascular diseases. J. Cell. Physiol. 224:262–272, 2010 © 2010 Wiley‐Liss, Inc.
Comparison of biological reactors (biofilter, biotrickling filter and modified RBC) for treating dichloromethane vapors
Authors: Ravi R. , Philip Ligy , Swaminathan T. 
Published: March 2010

AbstractBACKGROUND: Bioreactors used for waste gas and odor treatment have gained acceptance in recent years to treat volatile organic compounds (VOCs). Different types of bioreactors (biofilter, biotrickling filter and rotating biological reactor) have been used for waste gas treatment. Most studies reported in the literature have used one of these systems to treat several types of inorganic and organic gases either individually or in mixtures. Each of these reactors has some advantages and some limitations. Though biodegradation is the main process for the removal of pollutants, the mechanisms of removal and the microbial communities may differ among these bioreactors. Consequently their performance or removal efficiency may also be different.RESULTS: At low loading rate (<35 g m−3 h−1), all three bioreactors showed comparable removal efficiencies and elimination capacity, but at higher loading rates, rotating biological contactors (RBC) showed a better performance with higher removal efficiency (40–50%) than both the biofilter and biotrickling filter (20–40%). The biofilter showed a sharp drop in removal efficiency and elimination capacity at high loading rates.CONCLUSIONS: The modified RBC had no clogging problems and no increase in pressure drop when compared with the other bioreactors. It can thus handle pollutant load for a longer period of time. This is the first study attempting to compare the performance of three different bioreactors for removal of the same VOC under different conditions. Copyright © 2010 Society of Chemical Industry