bluuebunny/crossref_metadata_2025_split huggingface dataset:
CONTRIBUTION TO STUDY OF THE EFFECTS OF ADDITION OF PLASTICIZER AND OF AGEING ON THE VISCOELASTIC PROPERTIES OF POLYAMIDE
Authors: HADJADJ L. 
Published: July 2009

The purpose of this study is to obtain some information about the viscoelastic properties of the material and to see the effect of the addition of plasticizer on these properties. In particular, we try to study the loss of plasticizer, caused by ageing under conditions of utilization, on the properties of material at the neighborhood of vitreous transition. Using a viscoelastimeter, the study of a polyamide-11 (PA11) at the neighborhood of its temperature of vitreous transition Tv has shown that the increase of the plasticizer rate clearly improves the properties of the material by decreasing its Tv temperature. The comparison of the curves giving the modulus of elasticity E' of the various samples showed that the mechanical properties of the material improve with the increase of the concentration of plasticizer, but ageing reduces this improvement by causing the loss of plasticizer, thus, the temperature range of utilization of material is reduced.
Minimal Nielsen Root Classes and Roots of Liftings
Authors: Fenille Marcio Colombo , Neto Oziride Manzoli 
Published: July 2009

AbstractGiven a continuous map "Equation missing" from a 2-dimensional CW complex into a closed surface, the Nielsen root number "Equation missing" and the minimal number of roots "Equation missing" of "Equation missing" satisfy "Equation missing". But, there is a number "Equation missing" associated to each Nielsen root class of "Equation missing" and an important problem is to know when "Equation missing". In addition to investigate this problem, we determine a relationship between "Equation missing" and "Equation missing", when "Equation missing" is a lifting of "Equation missing" through a covering space, and we find a connection between this problems, with which we answer several questions related to them when the range of the maps is the projective plane.
Relaxed Composite Implicit Iteration Process for Common Fixed Points of a Finite Family of Strictly Pseudocontractive Mappings
Authors: Ceng L. C. , Shyu David S. , Yao J. C. 
Published: July 2009

AbstractWe propose a relaxed composite implicit iteration process for finding approximate common fixed points of a finite family of strictly pseudocontractive mappings in Banach spaces. Several convergence results for this process are established.
Nanoparticle-Delivered Suicide Gene Therapy Effectively Reduces Ovarian Tumor Burden in Mice
Authors: Huang Yu-Hung , Zugates Gregory T. , Peng Weidan , Holtz David , Dunton Charles , Green Jordan J. , Hossain Naushad , Chernick Michael R. , Padera Robert F. , Langer Robert , Anderson Daniel G. , Sawicki Janet A. 
Published: July 2009

Abstract
There is currently no effective therapy for patients with advanced ovarian cancer. To address the need for a more effective treatment for this deadly disease, we conducted preclinical tests in ovarian tumor–bearing mice to evaluate the therapeutic efficacy of using a cationic biodegradable poly(β-amino ester) polymer as a vector for nanoparticulate delivery of DNA encoding a diphtheria toxin suicide protein (DT-A). The promoter sequences of two genes that are highly active in ovarian tumor cells, MSLN and HE4, were used to target DT-A expression to tumor cells. Administration of DT-A nanoparticles directly to s.c. xenograft tumors and to the peritoneal cavity of mice bearing primary and metastatic ovarian tumors resulted in a significant reduction in tumor mass and a prolonged life span compared to control mice. Minimal nonspecific tissue and blood chemistry toxicity was observed following extended treatment with nanoparticles. DT-A nanoparticle therapy suppressed tumor growth more effectively than treatment with clinically relevant doses of cisplatin and paclitaxel. Our findings suggest that i.p. administration of polymeric nanoparticles to deliver DT-A encoding DNA, combined with transcriptional regulation to target gene expression to ovarian tumor cells, holds promise as an effective therapy for advanced-stage ovarian cancer. [Cancer Res 2009;69(15):6184–91]
The Development of a Selective Cyclin-Dependent Kinase Inhibitor That Shows Antitumor Activity
Authors: Ali Simak , Heathcote Dean A. , Kroll Sebastian H.B. , Jogalekar Ashutosh S. , Scheiper Bodo , Patel Hetal , Brackow Jan , Siwicka Alekasandra , Fuchter Matthew J. , Periyasamy Manikandan , Tolhurst Robert S. , Kanneganti Seshu K. , Snyder James P. , Liotta Dennis C. , Aboagye Eric O. , Barrett Anthony G.M. , Coombes R. Charles 
Published: July 2009

AbstractNormal progression through the cell cycle requires the sequential action of cyclin-dependent kinases CDK1, CDK2, CDK4, and CDK6. Direct or indirect deregulation of CDK activity is a feature of almost all cancers and has led to the development of CDK inhibitors as anticancer agents. The CDK-activating kinase (CAK) plays a critical role in regulating cell cycle by mediating the activating phosphorylation of CDK1, CDK2, CDK4, and CDK6. As such, CDK7, which also regulates transcription as part of the TFIIH basal transcription factor, is an attractive target for the development of anticancer drugs. Computer modeling of the CDK7 structure was used to design potential potent CDK7 inhibitors. Here, we show that a pyrazolo[1,5-a]pyrimidine–derived compound, BS-181, inhibited CAK activity with an IC50 of 21 nmol/L. Testing of other CDKs as well as another 69 kinases showed that BS-181 only inhibited CDK2 at concentrations lower than 1 μmol/L, with CDK2 being inhibited 35-fold less potently (IC50 880 nmol/L) than CDK7. In MCF-7 cells, BS-181 inhibited the phosphorylation of CDK7 substrates, promoted cell cycle arrest and apoptosis to inhibit the growth of cancer cell lines, and showed antitumor effects in vivo. The drug was stable in vivo with a plasma elimination half-life in mice of 405 minutes after i.p. administration of 10 mg/kg. The same dose of drug inhibited the growth of MCF-7 human xenografts in nude mice. BS-181 therefore provides the first example of a potent and selective CDK7 inhibitor with potential as an anticancer agent. [Cancer Res 2009;69(15):6208–15]
Vascular Endothelial Growth Factor-C Protects Prostate Cancer Cells from Oxidative Stress by the Activation of Mammalian Target of Rapamycin Complex-2 and AKT-1
Authors: Muders Michael H. , Zhang Heyu , Wang Enfeng , Tindall Donald J. , Datta Kaustubh 
Published: July 2009

Abstract
Recurrence and subsequent metastatic transformation of cancer develops from a subset of malignant cells, which show the ability to resist stress and to adopt to a changing microenvironment. These tumor cells have distinctly different growth factor pathways and antiapoptotic responses compared with the vast majority of cancer cells. Long-term therapeutic success can only be achieved by identifying and targeting factors and signaling cascades that help these cells survive during stress. Both microarray and immunohistochemical analysis on human prostate cancer tissue samples have shown an increased expression of vascular endothelial growth factor-C (VEGF-C) in metastatic prostate cancer. We have discovered that VEGF-C acts directly on prostate cancer cells to protect them against oxidative stress. VEGF-C increased the survival of prostate cancer cells during hydrogen peroxide stress by the activation of AKT-1/protein kinase Bα. This activation was mediated by mammalian target of rapamycin complex-2 and was not observed in the absence of oxidative stress. Finally, the transmembrane nontyrosine kinase receptor neuropilin-2 was found to be essential for the VEGF-C–mediated AKT-1 activation. Indeed, our findings suggest a novel and distinct function of VEGF-C in protecting cancer cells from stress-induced cell death, thereby facilitating cancer recurrence and metastasis. This is distinctly different from the known function of VEGF-C in inducing lymphangiogenesis. [Cancer Res 2009;69(15):6042–8]
Prolonged Cell Cycle Response of HeLa Cells to Low-Level Alkylation Exposure
Authors: Schroering Allen G. , Kothandapani Anbarasi , Patrick Steve M. , Kaliyaperumal Saravanan , Sharma Vishal P. , Williams Kandace J. 
Published: July 2009

Abstract
Alkylation chemotherapy has been a long-standing treatment protocol for human neoplasia. N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) is a direct-acting monofunctional alkylator. Temozolomide is a clinical chemotherapeutic equivalent requiring metabolic breakdown to the alkylating agent. Both chemicals have similar mechanistic efficacy against DNA mismatch repair–proficient tumor cells that lack expression of methylguanine methyltransferase. Clinically relevant concentrations of both agents affect replicating cells only after the first cell cycle. This phenomenon has been attributed to replication fork arrest at unrepaired O6-methyldeoxyguanine lesions mispaired with thymine during the first replication cycle. Here, we show, by several different approaches, that MNNG-treated tumor cells do not arrest within the second cell cycle. Instead, the population slowly traverses through mitosis without cytokinesis into a third cell cycle. The peak of both ssDNA and dsDNA breaks occurs at the height of the long mitotic phase. The majority of the population emerges from mitosis as multinucleated cells that subsequently undergo cell death. However, a very small proportion of cells, &lt;1:45,000, survive to form new colonies. Taken together, these results indicate that multinucleation within the third cell cycle, rather than replication fork arrest within the second cell cycle, is the primary trigger for cell death. Importantly, multinucleation and cell death are consistently avoided by a small percentage of the population that continues to divide. This information should prove clinically relevant for the future design of enhanced cancer chemotherapeutics. [Cancer Res 2009;69(15):6307–14]
Suppressor of Cytokine Signaling 3 Sensitizes Anaplastic Thyroid Cancer to Standard Chemotherapy
Authors: Francipane Maria Giovanna , Eterno Vincenzo , Spina Valentina , Bini Miriam , Scerrino Gregorio , Buscemi Giuseppe , Gulotta Gaspare , Todaro Matilde , Dieli Francesco , De Maria Ruggero , Stassi Giorgio 
Published: July 2009

Abstract
We previously showed that cancer cells from papillary, follicular, and anaplastic thyroid carcinomas produce interleukin-4 and interleukin-10, which counteract the cytotoxic activity of conventional chemotherapy through the up-regulation of antiapoptotic molecules. Here, we identify Janus kinase/signal transducers and activators of transcription (STAT) and phosphatidyl inositol 3-kinase (PI3K)/AKT as the down-stream pathways through which these cytokines confer resistance to cell death in thyroid cancer. We found that the absence of suppressors of cytokine signaling (SOCS) molecules allows the propagation of the survival signaling. Exogenous expression of SOCS1, SOCS3, and SOCS5 in the highly aggressive anaplastic thyroid cancer cells reduces or abolishes STAT3 and 6 phosphorylation and PI3K/Akt pathway activation resulting in alteration in the balance of proapoptotic and antiapoptotic molecules and sensitization to chemotherapeutic drugs in vitro. Likewise, exogenous expression of SOCS3 significantly reduces tumor growth and potently enhances the efficacy of chemotherapy in vivo. Our results indicate that SOCS3 regulation of cytokines-prosurvival programs might represent a new strategy to overcome the resistance to chemotherapy-induced cell death of thyroid cancer. [Cancer Res 2009;69(15):6141–8]
Differentiation of Lung Adenocarcinoma, Pleural Mesothelioma, and Nonmalignant Pulmonary Tissues Using DNA Methylation Profiles
Authors: Christensen Brock C. , Marsit Carmen J. , Houseman E. Andres , Godleski John J. , Longacker Jennifer L. , Zheng Shichun , Yeh Ru-Fang , Wrensch Margaret R. , Wiemels Joseph L. , Karagas Margaret R. , Bueno Raphael , Sugarbaker David J. , Nelson Heather H. , Wiencke John K. , Kelsey Karl T. 
Published: July 2009

Abstract
Pathologic differentiation of tissue of origin in tumors found in the lung can be challenging, with differentiation of mesothelioma and lung adenocarcinoma emblematic of this problem. Indeed, proper classification is essential for determination of treatment regimen for these diseases, making accurate and early diagnosis critical. Here, we investigate the potential of epigenetic profiles of lung adenocarcinoma, mesothelioma, and nonmalignant pulmonary tissues (n = 285) as differentiation markers in an analysis of DNA methylation at 1413 autosomal CpG loci associated with 773 cancer-related genes. Using an unsupervised recursively partitioned mixture modeling technique for all samples, the derived methylation profile classes were significantly associated with sample type (P &lt; 0.0001). In a similar analysis restricted to tumors, methylation profile classes significantly predicted tumor type (P &lt; 0.0001). Random forests classification of CpG methylation of tumors—which splits the data into training and test sets—accurately differentiated mesothelioma from lung adenocarcinoma over 99% of the time (P &lt; 0.0001). In a locus-by-locus comparison of CpG methylation between tumor types, 1266 CpG loci had significantly different methylation between tumors following correction for multiple comparisons (Q &lt; 0.05); 61% had higher methylation in adenocarcinoma. Using the CpG loci with significant differential methylation in a pathway analysis revealed significant enrichment of methylated gene-loci in Cell Cycle Regulation, DNA Damage Response, PTEN Signaling, and Apoptosis Signaling pathways in lung adenocarcinoma when compared with mesothelioma. Methylation profile–based differentiation of lung adenocarcinoma and mesothelioma is highly accurate, informs on the distinct etiologies of these diseases, and holds promise for clinical application. [Cancer Res 2009;69(15):6315–21]
Intravesical Immunotherapy of Superficial Bladder Cancer with Chitosan/Interleukin-12
Authors: Zaharoff David A. , Hoffman Benjamin S. , Hooper H. Brooks , Benjamin Compton J. , Khurana Kiranpreet K. , Hance Kenneth W. , Rogers Connie J. , Pinto Peter A. , Schlom Jeffrey , Greiner John W. 
Published: July 2009

AbstractIntravesical BCG has been used successfully to treat superficial bladder cancer for three decades. However, 20% to 30% of patients will fail initial BCG therapy and 30% to 50% of patients will develop recurrent tumors within 5 years. Alternative or complementary strategies for the management of superficial bladder cancer are needed. Interleukin-12 (IL-12) is a potent TH1 cytokine with robust antitumor activity and the ability to potentiate immunologic memory. Unfortunately, intravesical IL-12 did not show antitumor efficacy in a recent clinical study of patients with recurrent superficial bladder cancer. We hypothesized that coformulation of IL-12 with chitosan, a biocompatible, mucoadhesive polysaccharide, could improve intravesical IL-12 delivery and provide an effective and durable alternative for the treatment of superficial bladder cancer. In antitumor studies, 88% to 100% of mice bearing orthotopic bladder tumors were cured after four intravesical treatments with chitosan/IL-12. In contrast, only 38% to 60% of mice treated with IL-12 alone and 0% treated with BCG were cured. Antitumor responses following chitosan/IL-12 treatments were durable and provided complete protection from intravesical tumor rechallenge. Urinary cytokine analysis showed that chitosan/IL-12 induced multiple TH1 cytokines at levels significantly higher than either IL-12 alone or BCG. Immunohistochemistry revealed moderate to intense tumor infiltration by T cells and macrophages following chitosan/IL-12 treatments. Bladder submucosa from cured mice contained residual populations of immune cells that returned to baseline levels after several months. Intravesical chitosan/IL-12 is a well-tolerated, effective immunotherapy that deserves further consideration for testing in humans for the management of superficial bladder cancer. [Cancer Res 2009;69(15):6192–9]
Inhibition of Superoxide Generation upon T-Cell Receptor Engagement Rescues Mart-127-35–Reactive T Cells from Activation-Induced Cell Death
Authors: Norell Håkan , Martins da Palma Telma , Lesher Aaron , Kaur Navtej , Mehrotra Meenal , Naga Osama S. , Spivey Natalie , Olafimihan Seye , Chakraborty Nitya G. , Voelkel-Johnson Christina , Nishimura Michael I. , Mukherji Bijay , Mehrotra Shikhar 
Published: July 2009

AbstractCytotoxic T lymphocytes (CTL) may undergo massive expansion upon appropriate antigenic stimulation. Homeostasis is maintained by a subsequent “contraction” of these cells. Activation-induced cell death (AICD) and programmed cell death prevent the untoward side effects, arising from excessive numbers and prolonged persistence of activated CTL, that occur upon uncontrolled and/or continued expansion. However, effector cell persistence has been identified as a hallmark of successful T-cell–mediated adoptive immunotherapy. Thus, prevention of AICD may be critical to achieve more successful clinical results. We have previously shown that treatment with the c-Jun NH2-terminal kinase (JNK) inhibitor SP600125 protects human melanoma epitope Mart-127-35–reactive CTL from apoptotic death upon their reencounter with cognate antigen. However, inhibition of JNK also interferes with the functional ability of the CTL to secrete IFN-γ. Here, we show that reactive oxygen species (ROS) inhibitors, such as the superoxide dismutase mimetic Mn (III) tetrakis (5, 10, 15, 20-benzoic acid) porphyrin (MnTBAP), efficiently protected Mart-127-35–reactive primary CTL from AICD without impairing their functional capability. MnTBAP prevented the increase in intracellular ROS, mitochondrial membrane collapse, and DNA fragmentation observed in control-treated cells upon cognate antigen encounter. Furthermore, the mechanism of AICD prevention in primary CTL included blockade of JNK activation. Finally, tumor-reactive in vitro expanded tumor infiltrating lymphocytes, which are used clinically in cancer immunotherapy, also benefit from MnTBAP-mediated antioxidant treatment. Thus, modulation of the redox pathway might improve CTL persistence and lead to better clinical results for T cell–based immunotherapies. [Cancer Res 2009;69(15):6282–9]
The Neural Basis of Personal Goal Processing When Envisioning Future Events
Authors: D'Argembeau Arnaud , Stawarczyk David , Majerus Steve , Collette Fabienne , Van der Linden Martial , Feyers Dorothée , Maquet Pierre , Salmon Eric 
Published: July 2009

Abstract
Episodic future thinking allows humans to mentally simulate virtually infinite future possibilities, yet this device is fundamentally goal-directed and should not be equated with fantasizing or wishful thinking. The purpose of this fMRI study was to investigate the neural basis of such goal-directed processing during future-event simulation. Participants were scanned while they imagined future events that were related to their personal goals (personal future events) and future events that were plausible but unrelated to their personal goals (nonpersonal future events). Results showed that imaging personal future events elicited stronger activation in ventral medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC) compared to imaging nonpersonal future events. Moreover, these brain activations overlapped with activations elicited by a second task that assessed semantic self-knowledge (i.e., making judgments on one's own personality traits), suggesting that ventral MPFC and PCC mediate self-referential processing across different functional domains. It is suggested that these brain regions may support a collection of processes that evaluate, code, and contextualize the relevance of mental representations with regard to personal goals. The implications of these findings for the understanding of the function instantiated by the default network of the brain are also discussed.
The Role of Temporo-parietal Cortex in Subcortical Visual Extinction
Authors: Ticini Luca Francesco , de Haan Bianca , Klose Uwe , Nägele Thomas , Karnath Hans-Otto 
Published: July 2009

Abstract
Visual extinction is an intriguing defect of awareness in stroke patients, referring to the unsuccessful perception of contralesional events under conditions of competition. Previous studies have investigated the cortical and subcortical brain structures that, when damaged or inactivated, provoke visual extinction. The present experiment asked how lesions of subcortical structures may contribute to the appearance of visual extinction. We investigated whether lesions centering on right basal ganglia may induce dysfunction in distant, structurally intact cortical structures. Normalized perfusion-weighted MRI was used to identify structurally intact but abnormally perfused brain tissue, that is, zones that are receiving enough blood supply to remain structurally intact but not enough to function normally. We compared patients with right basal ganglia lesions showing versus not showing visual extinction. In the extinction patients, the contrast revealed cortical malperfusion that clustered around the right TPJ. It seems as if malfunction of this area is a critical aspect in visual extinction not only after cortical lesion but also in the case of subcortical basal ganglia damage. Our results support the idea that a normally functioning TPJ area plays a decisive role for the attentional network involved in detecting of visual stimuli under conditions of competition.
Approaching the Bad and Avoiding the Good: Lateral Prefrontal Cortical Asymmetry Distinguishes between Action and Valence
Authors: Berkman Elliot T. , Lieberman Matthew D. 
Published: July 2009

AbstractGoal pursuit in humans sometimes involves approaching unpleasant and avoiding pleasant stimuli, such as when a dieter chooses to eat vegetables (although he does not like them) instead of doughnuts (which he greatly prefers). Previous neuroscience investigations have established a left–right prefrontal asymmetry between approaching pleasant and avoiding unpleasant stimuli, but these investigations typically do not untangle the roles of action motivation (approach vs. avoidance) and stimulus valence (pleasant vs. unpleasant) in this asymmetry. Additionally, studies on asymmetry have been conducted almost exclusively using electroencephalography and have been difficult to replicate using functional magnetic resonance imaging (fMRI). The present fMRI study uses a novel goal pursuit task that separates action motivation from stimulus valence and a region-of-interest analysis approach to address these limitations. Results suggest that prefrontal asymmetry is associated with action motivation and not with stimulus valence. Specifically, there was increased left (vs. right) activation in dorsolateral prefrontal cortex during approach (vs. avoidance) actions regardless of the stimulus valence, but no such effect was observed for pleasant compared to unpleasant stimuli. This asymmetry effect during approach–avoidance action motivations occurred in the dorsolateral but not orbito-frontal aspects of prefrontal cortex. Also, individual differences in approach–avoidance motivation moderated the effect such that increasing trait approach motivation was associated with greater left-sided asymmetry during approach actions (regardless of the stimulus valence). Together, these results support the notion that prefrontal asymmetry is associated with action motivation regardless of stimulus valence and, as such, might be linked with goal pursuit processes more broadly.