bluuebunny/crossref_metadata_2025_split huggingface dataset:
Statins potentiate the in vitro anti-hepatitis C virus activity of selective hepatitis C virus inhibitors and delay or prevent resistance development #
Authors: Delang Leen , Paeshuyse Jan , Vliegen Inge , Leyssen Pieter , Obeid Susan , Durantel David , Zoulim Fabien , Op de Beeck Anne , Neyts Johan 
Published: February 2009

Abstract
Statins are 3-hydroxyl-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors used for the treatment of hypercholesterolemia. It was recently reported that statins inhibit in vitro hepatitis C virus (HCV) RNA replication. We here report that, of five statins studied, mevastatin and simvastatin exhibit the strongest in vitro anti-HCV activity, lovastatin and fluvastatin have moderate inhibitory effects, and pravastatin is devoid of an antiviral effect. A combination of statins with interferon-alpha (IFN-α) or HCV nonstructural (NS)5B polymerase or NS3 protease inhibitors results in an additive antiviral activity in short-term (3 days) antiviral assays. Neither statins, at a concentration of five-fold their median effective concentration (EC50) value, nor polymerase, protease inhibitors, or IFN-α, at concentrations 10- or 20-fold their EC50 value, were able to clear cells from their replicon following four or six consecutive passages of antiviral pressure. However, the combination of HCV polymerase or protease inhibitors with mevastatin or simvastatin resulted in an efficient clearance of the cultures from their replicon. In colony formation experiments, mevastatin reduced the frequency or prevented the selection of HCV replicons resistant to the nonnucleoside inhibitor HCV-796. Conclusion: A combination of specific HCV inhibitors with statins may result in a more profound antiviral effect and may delay or prevent the development of resistance to such inhibitors. (Hepatology 2009.)
L-ornithine phenylacetate attenuates increased arterial and extracellular brain ammonia and prevents intracranial hypertension in pigs with acute liver failure # †
Authors: Ytrebφ Lars Marius , Kristiansen Rune Gangsφy , Mæhre Hanne , Fuskevåg Ole Martin , Kalstad Trine , Revhaug Arthur , Cobos María Jover , Jalan Rajiv , Rose Christopher F. 
Published: February 2009

Abstract
Hyperammonemia is a feature of acute liver failure (ALF), which is associated with increased intracranial pressure (ICP) and brain herniation. We hypothesized that a combination of L-ornithine and phenylacetate (OP) would synergistically reduce toxic levels of ammonia by (1) L-ornithine increasing glutamine production (ammonia removal) through muscle glutamine synthetase and (2) phenylacetate conjugating with the ornithine-derived glutamine to form phenylacetylglutamine, which is excreted into the urine. The aims of this study were to determine the effect of OP on arterial and extracellular brain ammonia concentrations as well as ICP in pigs with ALF (induced by liver devascularization). ALF pigs were treated with OP (L-ornithine 0.07 g/kg/hour intravenously; phenylbutyrate, prodrug for phenylacetate; 0.05 g/kg/hour intraduodenally) for 8 hours following ALF induction. ICP was monitored throughout, and arterial and extracellular brain ammonia were measured along with phenylacetylglutamine in the urine. Compared with ALF + saline pigs, treatment with OP significantly attenuated concentrations of arterial ammonia (589.6 ± 56.7 versus 365.2 ± 60.4 μmol/L [mean ± SEM], P= 0.002) and extracellular brain ammonia (P= 0.01). The ALF-induced increase in ICP was prevented in ALF + OP-treated pigs (18.3 ± 1.3 mmHg in ALF + saline versus 10.3 ± 1.1 mmHg in ALF + OP-treated pigs; P= 0.001). The value of ICP significantly correlated with the concentration of extracellular brain ammonia (r
2 = 0.36, P< 0.001). Urine phenylacetylglutamine levels increased to 4.9 ± 0.6 μmol/L in ALF + OP-treated pigs versus 0.5 ± 0.04 μmol/L in ALF + saline-treated pigs (P< 0.001). Conclusion: L-Ornithine and phenylacetate act synergistically to successfully attenuate increases in arterial ammonia, which is accompanied by a significant decrease in extracellular brain ammonia and prevention of intracranial hypertension in pigs with ALF. (Hepatology 2009;50:165–174.)
MicroRNA-195 suppresses tumorigenicity and regulates G1/S transition of human hepatocellular carcinoma cells #
Authors: Xu Teng , Zhu Ying , Xiong Yujuan , Ge Yi-Yuan , Yun Jing-Ping , Zhuang Shi-Mei 
Published: February 2009

Abstract
Growing evidence indicates that deregulation of microRNAs (miRNAs) contributes to tumorigenesis. Down-regulation of miR-195 has been observed in various types of cancers. However, the biological function of miR-195 is still largely unknown. In this study we aimed to elucidate the pathophysiologic role of miR-195. Our results showed that miR-195 expression was significantly reduced in as high as 85.7% of hepatocellular carcinoma (HCC) tissues and in all of the five HCC cell lines examined. Moreover, introduction of miR-195 dramatically suppressed the ability of HCC and colorectal carcinoma cells to form colonies in vitro and to develop tumors in nude mice. Furthermore, ectopic expression of miR-195 blocked G1/S transition, whereas inhibition of miR-195 promoted cell cycle progression. Subsequent investigation characterized multiple G1/S transition-related molecules, including cyclin D1, CDK6, and E2F3, as direct targets of miR-195. Silencing of cyclin D1, CDK6, or E2F3 phenocopied the effect of miR-195, whereas overexpression of these proteins attenuated miR-195-induced G1 arrest. In addition, miR-195 significantly repressed the phosphorylation of Rb as well as the transactivation of downstream target genes of E2F. These results imply that miR-195 may block the G1/S transition by repressing Rb-E2F signaling through targeting multiple molecules, including cyclin D1, CDK6, and E2F3. Conclusion: Our data highlight an important role of miR-195 in cell cycle control and in the molecular etiology of HCC, and implicate the potential application of miR-195 in cancer therapy. (Hepatology 2009.)
Neurocognitive effects of switching from methylphenidate‐IR to OROS‐methylphenidate in children with ADHD
Authors: Kim Yeni , Shin Min‐Sup , Kim Jae‐Won , Yoo Hee‐Jung , Cho Soo‐Churl , Kim Boong‐Nyun 
Published: February 2009

AbstractObjectivesThis study evaluated neurocognitive changes after switching from immediate release forms of methylphenidate (MPH‐IR) to osmotic release oral system methylphenidate (OROS‐MPH).Methods102 children with attention‐deficit/hyperactivity disorder (ADHD) participated in an open label, 28 day trial, performing neurocognitive test at baseline and at 28 days after the switch from MPH‐IR to OROS‐MPH.ResultsThere were significant improvements in the commission error and the reaction time of both visual and auditory continuous performance tests (CPTs) at 28 days after switching from MPH‐IR to OROS‐MPH. A positive correlation was observed between the improvement in parent/caregiver‐rated IOWA Conners total score (Δ IOWA) and the reduction in commission error (r = 0.3, p = 0.001) and reduction in reaction time variability (r = 0.3, p = 0.006) of visual CPT. In a linear regression model, the change in parent/caregiver‐rated IOWA Conners scale total scores were significant predictors of change in commission error (β = 0.3, p = 0.005, CI = 0.4–2.3, adjusted R2 = 0.12) and RT variability (β = 0.3, p = 0.004, CI = 0.5–2.4, adjusted R2 = 0.09) of visual CPT.ConclusionsThese data suggest that MPH‐IR may be successfully switched to OROS‐MPH treatment with associated improvements in neurocognitive performance. Large‐scale controlled trials are needed to replicate these findings. Copyright © 2009 John Wiley & Sons, Ltd.
In vitro induction of apoptosis and in vivo effects of a flavone nitroderivative in murine mammary adenocarcinoma cells
Authors: Cárdenas Mariano G. , Zotta Elsa , Marder Mariel , Roguin Leonor P. 
Published: February 2009

AbstractWe explored thein vitroandin vivomechanism of antitumor action of the synthetic flavonoid 2′‐nitroflavone on LM3 murine mammary adenocarcinoma cells.In vitroassays showed that 2′‐nitroflavone increased the population of LM3 hypodiploid cells and produced a typical ladder of DNA fragmentation. Apoptotic cell death was also characterized by the activation of caspase‐8, ‐9 and ‐3, by an increment in the expression levels of the proapoptotic protein Bax and by the release of cytochromecto cytosol. Thein vivoeffect of 2′‐nitroflavone on tumor growth was studied in BALB/c mice injected subcutaneously with LM3 cells. Results showed that tumor volume and weight were significantly reduced at doses of 10 and 40 mg/kg of 2′‐nitroflavone, respectively. Apoptotic cells were identified by TUNEL assay in tumor slices from mice treated with 10 mg/kg of 2′‐nitroflavone. Western blot analysis of tumor lysate supernatants from treated mice revealed an upregulation of the total levels of Bax and Fas receptor. In addition, administration of 40 mg/kg of 2′‐nitroflavone to nontumor‐bearing mice showed no histopathological effects on different organ tissues. This is the first report of thein vivogrowth inhibitory effect of 2′‐nitroflavone as an apoptotic agent likely useful for mammary adenocarcinoma treatment. © 2009 UICC
Childhood leukemias and other hematopoietic malignancies: Interdependence between an infectious event and chromosomal modifications
Authors: zur Hausen Harald 
Published: February 2009

AbstractA large number of epidemiological observations suggest an infectious origin of hematopoietic malignancies, including various forms of leukemia, nonHodgkin's lymphomas, Hodgkin's lymphomas and multiple myelomas. Incidence of nonHodgkin's lymphomas and Hodgkin's lymphomas, although not of leukemias, is substantially increased under immunosuppression. Specific chromosomal modifications (translocations) resulting in fusion genes frequently emerge as early, but not sufficient, events for malignant progression in most of these conditions. Presently less than 10% of the global incidence of leukemias and lymphomas can be linked to infections (Epstein‐Barr virus, human T‐lymphotropic retrovirus, human herpesvirus type 8 and Helicobacter pylori). For individual tumor types of the remaining more than 90%, several risk factors have been identified. They include occupational hazards, such as engagement in community services and agriculture, as well as time–space clustering. In childhood leukemias, a protective effect was noted for multiple infections during the first year of life and for at least 6 months of breastfeeding. A high socioeconomic state and absence of multiple contacts during the early phase of life have been described as risk factors. A hypothesis is presented here which combines these observations. It postulates a wide‐spread viral infection, nontumorigenic when replication competent, but potentially leukemiogenic or carcinogenic when replication‐incompetent viral genomes infect cells with specific chromosomal modifications. Existing data on polyoma‐like virus types seem to render members of this or structurally related virus families as putative candidates for these malignancies. © 2009 UICC
WT1 IgG antibody for early detection of nonsmall cell lung cancer and as its prognostic factor
Authors: Oji Yusuke , Kitamura Yayoi , Kamino Eriko , Kitano Aiko , Sawabata Noriyoshi , Inoue Masayoshi , Mori Masahide , Nakatsuka Shin‐ichi , Sakaguchi Nao , Miyazaki Kaori , Nakamura Michiyo , Fukuda Ikuyo , Nakamura Junya , Tatsumi Naoya , Takakuwa Tetsuya , Nishida Sumiyuki , Shirakata Toshiaki , Hosen Naoki , Tsuboi Akihiro , Nezu Riichiro , Maeda Hajime , Oka Yoshihiro , Kawase Ichiro , Aozasa Katsuyuki , Okumura Meinoshin , Miyoshi Shinichiro , Sugiyama Haruo 
Published: February 2009

AbstractThere are urgent needs to develop methods for early detection of nonsmall cell lung cancer (NSCLC) because of its increasing incidence and poor prognosis. Here, we analyzed the production of IgG antibody (WT1 Ab) against WT1 (Wilms' tumor gene) protein that was overexpressed in the majority of NSCLC. Enzyme‐linked immuno‐sorbent assay showed that WT1 Ab was produced in all of 91 NSCLC patients and 70 healthy individuals and that WT1 Ab titers were significantly higher in NSCLC patients compared with healthy individuals. When the cut‐off level of WT1 Ab titers were fixed at mean + 3SD of those in healthy individuals, 26.4% of NSCLC patients had WT1 Ab titers over the cut‐off level, and positive rates of WT1 Ab at each clinical stage were 25.0, 30.8 and 38.4% in stage I, II and III NSCLC, respectively. When WT1 Ab was combined with CEA or CYFRA for detection of NSCLC, positive detection rates increased from 25.0 to 34.1 and 31.8%, respectively, in stage I and from 38.4 to 69.2 and 46.1%, respectively, in stage III, but not changed in stage II. Western blot analysis showed that dominant subclass of WT1 Ab was Th1‐type IgG2. Interestingly, elevation of WT1 Ab titers was significantly associated with longer disease‐free survival in patients with stages I–III NSCLC. These results showed that WT1 Ab could be a useful marker for early detection of NSCLC and its prognostic prediction. These results also suggested that WT1‐specific immune responses played an important role in anti‐cancer immunity in NSCLC. © 2009 UICC
IgE, allergy, and risk of glioma: Update from the San Francisco Bay Area Adult Glioma Study in the Temozolomide era
Authors: Wiemels Joseph L. , Wilson David , Patil Chirag , Patoka Joseph , McCoy Lucie , Rice Terri , Schwartzbaum Judith , Heimberger Amy , Sampson John H. , Chang Susan , Prados Michael , Wiencke John K. , Wrensch Margaret 
Published: February 2009

AbstractThe consistently observed inverse relationship of allergic conditions with glioma risk and our previous demonstration that immunoglobulin E (IgE) levels also were lower in glioma patients than controls suggest that atopic allergy may be related to a mechanism that inhibits or prevents glioma. We sought to extend these results with a new and larger series of patients (n = 535 with questionnaire data; 393 with IgE measures) and controls (n = 532 with questionnaire data; 470 with IgE measures). As expected, glioma cases were less likely than controls to report history of allergies [among self‐reported cases, Odds ratios (OR) = 0.59, 95% confidence interval (CI): 0.41–0.85]. IgE levels also were lower in glioma cases versus controls (OR per unit log IgE = 0.89, 95% CI (0.82–0.98). However, this inverse relationship was only apparent among cases receiving temozolomide, a treatment which became part of the “standard of care” for glioblastoma patients during the study period. Among patients receiving temozolomide, IgE levels in cases whose blood samples were obtained within 30 days of diagnosis were slightly higher than controls, whereas IgE levels in cases whose blood sample was obtained >60 days after diagnosis were significantly lower than controls (OR = 0.80; 95% CI: 0.71–0.89). Thus, although our results robustly confirm the inverse association between allergy and glioma, the results for IgE are affected by temozolomide treatments which may have influenced IgE levels. These results have implications for the study of immunologic factors in glioma as well as for immunotherapy protocols for treating glioma. © 2009 UICC
Mass screening for colorectal cancer is not justified in most developing countries
Authors: Lambert René , Sauvaget Catherine , Sankaranarayanan Rengaswamy 
Published: February 2009

AbstractMost developed countries insist on the prevention of colorectal cancer (CRC) and offer screening to the population. Mass screening is proposed to both sexes in the population aged 50 years or more. Colonoscopy is then offered to persons having a positive faecal occult blood test. This recommendation should not be diffused over the world without considering the distinct dimensions of the risk and resources in developed and developing countries. A national screening policy is legitimate in developed countries like Japan, South Korea, and in North America and Europe. On the other hand, a mass screening policy for CRC is not recommended in most developing countries. The limited amount of resources attributed to health care for cancer should concern other indications in the control of common cancers, particularly in the cervix or liver. Indeed the risk of CRC is very low in most regions of Africa, and in some countries of South America and Asia. © 2009 UICC
Estrogen regulation of thrombospondin‐1 in human breast cancer cells
Authors: Hyder Salman M. , Liang Yayun , Wu Jianbo 
Published: February 2009

AbstractExpression of thrombospondin‐1 (TSP‐1), a large extracellular matrix protein, has been associated with modulation of angiogenesis and tumor growth. Both pro and antiangiogenic properties of TSP‐1 have been described, and the role of TSP‐1 expression in the growth and progression of human breast cancer is not clear. Because estrogens cause progression of many breast cancers, and estradiol (E2) downregulates a TSP‐1 receptor, we examined whether TSP‐1 is regulated by estrogen and involved in tumor progression. E2 induced TSP‐1 expression in T47‐D and MCF‐7 breast cancer cells in vitro within 3 to 6 hr; the induction was blocked by the anti‐estrogen ICI 182,780, indicating that estrogen receptors (ER) are necessary for this effect. Furthermore, E2 caused the production of TSP‐1 protein from tumor cells in an ER‐alpha‐dependent manner. The E2‐mediated TSP‐1 RNA induction was dose‐dependent and blocked by actinomycin D, indicating that the response to E2 was at least partly transcriptional. Transfection studies with deletion constructs of the TSP‐1 promoter identified an estrogen‐responsive region in the human TSP‐1 promoter, located between −2,200 and −1,792 bp upstream of the transcription start site. An antibody against TSP‐1 restricted the proliferation of E2‐dependent MCF‐7 cells in vitro and in vivo. A panel of breast cancer cells proliferated in the presence of low concentrations of exogenous TSP‐1, whereas higher concentrations inhibited proliferation. A real‐time PCR analysis showed that E2 also induced TSP‐1 mRNA in the normal mammary glands of immature ovariectomized mice in an ER‐dependent manner. In summary, we report the novel observation that TSP‐1 production is directly controlled by estrogens in ER‐positive breast cancer cells, and the released protein has pro‐growth regulatory functions. Consequently, we propose that TSP‐1 could be a therapeutic target for anti‐tumor therapy in early‐stage tumors. © 2009 UICC
The Akt inhibitor triciribine sensitizes prostate carcinoma cells to TRAIL‐induced apoptosis
Authors: Dieterle Alexandra , Orth Ronald , Daubrawa Merle , Grotemeier Antje , Alers Sebastian , Ullrich Susanne , Lammers Reiner , Wesselborg Sebastian , Stork Björn 
Published: February 2009

AbstractAberrant PI3K/Akt signaling has been implicated in many human cancers, including prostate carcinomas. Currently different therapeutic strategies target the inhibition of this survival pathway. The nucleoside analog triciribine (TCN), which was initially described as a DNA synthesis inhibitor, has recently been shown to function as an inhibitor of Akt. Here, we demonstrate that TCN inhibits Akt phosphorylation at Thr308 and Ser473 and Akt activity in the human prostate cancer cell line PC‐3. In addition, TCN sensitized PC‐3 cells to TRAIL‐ and anti‐CD95‐induced apoptosis, whereas the cells remained resistant to DNA damaging chemotherapeutics. The observed sensitization essentially depended on the phosphorylation status of Akt. Thus, prostate cancer cell lines displaying constitutively active Akt, e.g. PC‐3 or LNCaP, were sensitized to death receptor‐induced apoptosis. Most importantly with respect to therapeutic application, derivatives of both TCN and TRAIL are already tested in current clinical trials. Therefore, this combinatorial treatment might open a promising therapeutic approach for the elimination of hormone‐refractory prostate cancers, which are largely resistant to conventional DNA damaging anticancer drugs or irradiation. © 2009 UICC
Blockade of MEK signaling potentiates 5‐Aza‐2′‐deoxycytidine‐induced apoptosis and upregulation of p21waf1 in acute myelogenous leukemia cells
Authors: Nishioka Chie , Ikezoe Takayuki , Yang Jing , Komatsu Naoki , Koeffler H. Phillip , Yokoyama Akihito 
Published: February 2009

AbstractWe have recently reported that the mitogen‐activated protein kinase/ERK kinase (MEK) inhibitor AZD6244 (ARRY‐142886) strikingly potentiated the effects of histone deacetylase inhibitor to induce growth arrest and apoptosis of acute myelogeneous leukemia (AML) cells in association with enhanced upregulation of p21waf1. This study examined the effects of the MEK inhibitor on the action of DNA methyltransferase inhibitor 5‐Aza‐2′‐deoxycytidine (5‐AzadC), another epigenetic agent in AML cells. AZD6244 significantly potentiated the ability of 5‐AzadC to induce growth arrest and apoptosis of NB4, and freshly isolated AML cells. In parallel, 5‐AzadC induced expression of p21waf1 in AML cells, which was potently enhanced in the presence of AZD6244. Further studies explored the molecular mechanisms by which 5‐AzadC induced expression of p21waf1 and found that a low dose of 5‐AzadC (1 μM) induced acetylation of histone H3 on the p21waf1 gene promoter; however, higher dose of this compound (3 or 5 μM) potently induced DNA damage as assessed by expression of γH2AX, in NB4 cells. These effects were strikingly enhanced by concomitant blockade of MEK signaling. Furthermore, knock‐down of p21waf1 by the siRNA rescued NB4 cells from 5‐AzadC‐mediated growth inhibition. Taken together, combination of 5‐AzadC and the MEK inhibitor may be useful for treatment of individuals with a subset of AML. © 2009 UICC
The impact of client treatment preferences on outcome: a meta‐analysis
Authors: Swift Joshua K. , Callahan Jennifer L. 
Published: February 2009

AbstractAn important part of evidence‐based practice is to include client preferences in the treatment decision‐making process. However, based on previous reviews of the literature there is some question as to whether including client preferences actually has an effect on treatment outcome. This meta‐analytic review summarized data from over 2,300 clients across 26 studies comparing the treatment outcome differences between clients matched to a preferred treatment and clients not matched to a preferred treatment. The findings indicate a small significant effect (r=.15, CI.95: .09 to .21) in favor of clients who received a preferred treatment. The binomial effect size indicated that matched clients have a 58% chance of showing greater improvement, and further analysis indicate that they are about half as likely to drop‐out of treatment when compared with clients not receiving a preferred treatment. Study design was seen to be a moderating variable in that partially randomized preference trials may underestimate the treatment preference effect. Implications for best practice standards are discussed. © 2009 Wiley Periodicals, Inc. J Clin Psychol 65:1–14, 2009.