bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potent synergy of dual antitumor peptides for growth suppression of human glioblastoma cell lines
Authors: Kondo Eisaku , Tanaka Takehiro , Miyake Takayoshi , Ichikawa Tomotsugu , Hirai Masahiko , Adachi Masaki , Yoshikawa Kazuhiro , Ichimura Koichi , Ohara Nobuya , Moriwaki Akiyoshi , Date Isao , Ueda Ryuzo , Yoshino Tadashi 
Published: June 2008

Abstract
Molecular targeting agents have become formidable anticancer weapons, which show much promise against the refractory tumors. Functional peptides are among the more desirable of these nanobio-tools. Intracellular delivery of multiple functional peptides forms a basis for potent, non-invasive mode of delivery, providing distinctive therapeutic advantages. Here, we examine growth suppression efficiency of human glioblastomas by dual-peptide targeting. We did simultaneous introduction of two tumor suppressor peptides (p14ARF and p16INK4a or p16INK4a and p21CIP1 functional peptides) compared with single-peptide introduction using Wr-T-mediated peptide delivery. Wr-T-mediated transport of both p14ARF and p16INK4a functional peptides (p14-1C and p16-MIS, respectively) into human glioblastoma cell line, U87ΔEGFR, reversed specific loss of p14 and p16 function, thereby drastically inhibiting tumor growth by &gt;95% within the first 72 h, whereas the growth inhibition was ∼40% by p14 or p16 single-peptide introduction. Additionally, the combination of p16 and p21CIP1 (p21-S154A) peptides dramatically suppressed the growth of glioblastoma line Gli36ΔEGFR, which carries a missense mutation in p53, by &gt;97% after 120 h. Significantly, our murine brain tumor model for dual-peptide delivery showed a substantial average survival enhancement (P &lt; 0.0001) for peptide-treated mice. Wr-T-mediated dual molecular targeting using antitumor peptides is highly effective against growth of aggressive glioblastoma cells in comparison with single molecule targeting. Thus, jointly restoring multiple tumor suppressor functions by Wr-T-peptide delivery represents a powerful approach, with mechanistic implications for development of efficacious molecular targeting therapeutics against intractable human malignancies. [Mol Cancer Ther 2008;7(6):1461–71]
DNA vaccination with CD44 variant isoform reduces mammary tumor local growth and lung metastasis
Authors: Wallach-Dayan Shulamit Batya , Rubinstein Ariel M. , Hand Carla , Breuer Raphael , Naor David 
Published: June 2008

AbstractWe have shown recently that cDNA vaccination, using a virtual lymph node, ameliorates experimental allergic encephalomyelitis. Successful cure from mammary tumor requires resolution of local tumor growth and metastases. We have examined whether targeting of CD44 cell surface adhesion molecule by cDNA vaccination plays a role in resolving mammary tumor development. We show here that CD44 cDNA vaccination decreases the tumor mass and metastatic potential in experimental mammary tumor of BALB/c mice. Vaccination of mice, inoculated with the mammary tumors, by cDNA of CD44 variant (CD44v) but not by cDNA of standard CD44, markedly reduced local tumor development and lung metastasis. Concomitantly, transfection of CD44 antisense into a highly metastatic mammary tumor cell line disrupted the CD44 expression of the cells and reduced their ability to establish local tumors as well as metastatic colonies in the lung. Moreover, when CD44v, but not standard CD44 sense cDNA, was transfected into the poorly metastatic cell line, tumor development was markedly enhanced. It is possible therefore that DNA vaccination with a specific CD44v construct could induce an immune resistance to mammary tumor progression. [Mol Cancer Ther 2008;7(6):1615–23]
Insulin-like growth factor-I receptor blockade by a specific tyrosine kinase inhibitor for human gastrointestinal carcinomas
Authors: Piao Wenhua , Wang Yu , Adachi Yasushi , Yamamoto Hiroyuki , Li Rong , Imsumran Arisa , Li Hua , Maehata Tadateru , Li Masanori , Arimura Yoshiaki , Lee Choon-Taek , Shinomura Yasuhisa , Carbone David P. , Imai Kohzoh 
Published: June 2008

Abstract
Insulin-like growth factor-I receptor (IGF-IR) signaling is required for carcinogenicity and proliferation of gastrointestinal (GI) cancers. In this study, we sought to evaluate the effect of a new tyrosine kinase inhibitor of IGF-IR, NVP-AEW541, on the signal transduction and the progression of GI carcinomas. We assessed the effect of NVP-AEW541 on signal transduction, proliferation, survival, and migration in four GI cancer cells: colorectal adenocarcinoma HT29, pancreatic adenocarcinoma BxPC3, esophageal squamous cell carcinoma TE1, and hepatoma PLC/PRF/5. The effects of NVP-AEW541 alone and with chemotherapy were studied in vitro and in nude mouse xenografts. We also analyzed the effects of NVP-AEW541 on insulin signals and hybrid receptor formation between IGF-IR and insulin receptor. NVP-AEW541 blocked autophosphorylation of IGF-IR and both Akt and extracellular signal-regulated kinase activation by IGF but not by insulin. NVP-AEW541 suppressed proliferation and tumorigenicity in vitro in a dose-dependent manner in all cell lines. The drug inhibited tumor as a single agent and, when combined with stressors, up-regulated apoptosis in a dose-dependent fashion and inhibited mobility. NVP-AEW541 augmented the effects of chemotherapy on in vitro growth and induction of apoptosis. Moreover, the combination of NVP-AEW541 and chemotherapy was highly effective against tumors in mice. This compound did not influence hybrid receptor formation. Thus, NVP-AEW541 may have significant therapeutic utility in human GI carcinomas both alone and in combination with chemotherapy. [Mol Cancer Ther 2008;7(6):1483–93]
A novel triple-regulated oncolytic adenovirus carrying p53 gene exerts potent antitumor efficacy on common human solid cancers
Authors: Wang Xinghua , Su Changqing , Cao Hui , Li Kui , Chen Jie , Jiang Lixin , Zhang Qi , Wu Xiaobing , Jia Xiaoyuan , Liu Yongjing , Wang Weiguo , Liu Xinyuan , Wu Mengchao , Qian Qijun 
Published: June 2008

Abstract
Conditionally replicating adenoviruses (CRAd) can replicate specifically in cancer cells and lyse them. The CRAds were widely used in the preclinical and clinical studies of cancer therapy. We hypothesize that more precisely regulated replication of CRAds may further improve the vector safety profile and enhance its antitumor efficacy. Here, a triple-regulated CRAd carrying p53 gene expression cassette, SG600-p53, was engineered. In SG600-p53, the E1a gene with a deletion of 24 nucleotides within CR2 region is controlled under the human telomerase reverse transcriptase (hTERT) promoter, the E1b gene expression is directed by the hypoxia response element (HRE), whereas the p53 gene is controlled by the cytomegalovirus promoter. The precise triple-regulation endows SG600-p53 with enhanced antitumor potential and improved safety profile. The tumor-selective replication of this virus and its antitumor efficacy were characterized in several tumor cell lines in vitro and in xenograft models of human non-small cell lung cancer in nude mice. With the selective replication and oncolysis, it was found by ELISA assay that SG600-p53 expressed p53 efficiently in cancer cells. In NCI-H1299 tumor xenograft models, SG600-p53 displayed a tumor-selective killing capacity. At a dose of 2 × 109 plaque-forming units, SG600-p53 could completely inhibit the tumor growth and more effective than replication-defective Ad-p53. Histopathologic examination revealed that SG600-p53 administration resulted in cancer cell apoptosis. We concluded that the triple-regulated SG600-p53, as a more potent and safer antitumor therapeutic, could provide a new strategy for cancer biotherapy. [Mol Cancer Ther 2008;7(6):1598–603]
Bortezomib induces apoptosis via Bim and Bik up-regulation and synergizes with cisplatin in the killing of head and neck squamous cell carcinoma cells
Authors: Li Changyou , Li Rongxiu , Grandis Jennifer R. , Johnson Daniel E. 
Published: June 2008

Abstract
Head and neck squamous cell carcinomas (HNSCC) are characterized by resistance to chemotherapy and overexpression of antiapoptotic Bcl-2 family members, including Bcl-XL and Bcl-2. Molecular targeting of Bcl-XL and/or Bcl-2 in HNSCC cells has been shown to promote apoptosis signaling and to sensitize cells to chemotherapy drugs, including cisplatin, which is commonly used in the treatment of HNSCC. We report that induction of HNSCC apoptosis by the proteasome inhibitor bortezomib is accompanied by up-regulation of the proapoptotic proteins Bik and Bim, natural cellular inhibitors of Bcl-XL and Bcl-2. Additionally, bortezomib treatment of HNSCC cells caused up-regulation of antiapoptotic Mcl-1L. Inhibition of Bik or Bim up-regulation using small interfering RNA markedly attenuated bortezomib-induced cell death. By contrast, small interfering RNA–mediated inhibition of Mcl-1L expression resulted in enhanced killing by bortezomib. Further investigation showed that the combination of bortezomib and cisplatin led to synergistic killing of HNSCC cells, with calculated combination indexes well below 1.0. Taken together, these results delineate a novel mechanism of HNSCC killing by bortezomib that involves up-regulation of Bik and Bik. Moreover, our findings suggest that the combination of bortezomib plus cisplatin, or bortezomib plus an inhibitor of Mcl-1L, may have therapeutic value in the treatment of HNSCC. [Mol Cancer Ther 2008;7(6):1647–55]
STAT3 inhibition in prostate and pancreatic cancer lines by STAT3 binding sequence oligonucleotides: differential activity between 5′ and 3′ ends
Authors: Lewis H. Dan , Winter Ashley , Murphy Thomas F. , Tripathi Snehlata , Pandey Virendra N. , Barton Beverly E. 
Published: June 2008

Abstract
Signal transducers and activators of transcription (STAT) were originally discovered as components of signal transduction pathways. Persistent aberrant activation of STAT3 is a feature of many malignancies including prostate cancer and pancreatic cancer. One consequence of persistently activated STAT3 in malignant cells is that they depend on it for survival; thus, STAT3 is an excellent molecular target for therapy. Previously, we reported that single-stranded oligonucleotides containing consensus STAT3 binding sequences (13410 and 13411) were more effective for inducing apoptosis in prostate cancer cells than antisense STAT3 oligonucleotides. Control oligonucleotides (scrambled sequences) had no effect. Here, we report that authentic STAT3 binding sequences, identified from published literature, were more effective for inducing apoptosis in prostate cancer cells and pancreatic cancer cells than was oligonucleotide 13410. Moreover, the authentic STAT3 binding sequences showed differing efficacies in the malignant cell lines depending on whether the canonical STAT3 binding sequence was truncated at the 5′ or the 3′ end. Finally, expression of one STAT3-regulated gene was decreased following treatment, suggesting that STAT3 may regulate the same set of genes in the two types of cancer. We conclude that truncating the 5′ end left intact enough of the canonical STAT3 binding site for effective hybridization to the genome, whereas truncation of the 3′ end, which is outside the canonical binding site, may have affected binding of required cofactors essential for STAT3 activity, thereby reducing the capacity of this modified oligonucleotide to induce apoptosis. Additional experiments to answer this hypothesis are under way. [Mol Cancer Ther 2008;7(6):1543–50]
Neural Correlates of Stereotype Application
Authors: Mitchell Jason P. , Ames Daniel L. , Jenkins Adrianna C. , Banaji Mahzarin R. 
Published: June 2008

Abstract
Recent research has focused on the disparate mechanisms that support the human ability to “mentalize” about the thoughts and feelings of others. One such process may rely on precompiled, semantic beliefs about the characteristics common to members of a social group, that is, on stereotypes; for example, judging that a woman may be more likely than a man to have certain interests or opinions. In the current study, we identified a pattern of neural activity associated with the use of stereotypes to judge another person's psychological characteristics. During fMRI scanning, participants mentalized about the likely responses of a female and male target to a series of questions, some of which were related to gender stereotypes (e.g., “enjoys shopping for new clothes”). Trials on which participants applied a stereotype were segregated from those on which participants avoided stereotype use. The BOLD response in an extensive region of the right frontal cortex differentiated stereotype-applied from -unapplied trials. Moreover, this neural difference was correlated with a behavioral index of gender associations—the Implicit Association Test—administered after scanning. Results suggest that stereotype application may draw on cognitive processes that more generally subserve semantic knowledge about categories.
Hemisphere-specific Episodic Memory Networks in the Human Brain: A Correlation Study between Intracarotid Amobarbital Test and [18F]FDG-PET
Authors: Akanuma Nozomi , Reed Laurence J. , Marsden Paul K. , Jarosz Jozeph , Adachi Naoto , Hallett William A. , Alarcón Gonzalo , Morris Robin G. , Koutroumanidis Michael 
Published: June 2008

Abstract
The purpose of the present study was to explore the brain regions involved in human episodic memory by correlating unilateral memory performance estimated by the intracarotid amobarbital test (IAT) and interictal cerebral metabolism measured by [18F]fluorodeoxyglucose positron emission tomography ([18F]FDG-PET). Using this method, regional alterations of cerebral metabolism associated with epilepsy pathophysiology are used to predict hemisphere-specific episodic memory function, hence, investigate the differential distribution of memory in each hemisphere. Sixty-two patients with unilateral temporal lobe epilepsy (35 left and 27 right) were studied using [18F]FDG-PET with complementary voxel-based statistical parametric mapping (SPM) and region-of-interest (ROI) methods of analysis. Positive regression was analyzed in SPM with a series of different thresholds (p = .001, .01 or .05) with a correction to 100 voxels. IAT memory performance in which left hemisphere was tested by right-sided injection of amobarbital correlated with [18F]FDG uptake in left lateral and medial temporal regions, and in the left ventrolateral frontal cortex. Right IAT memory performance correlated with [18F]FDG uptake in the right inferior parietal lobule, right dorsolateral frontal cortex, right precentral gyrus, and caudal portion of the right anterior cingulate cortex. ROI analysis corroborated these results. Analyses carried out separately in patients with left (n = 50) and nonleft (n = 12) dominance for language showed that in the nonleft dominant group, right IAT scores correlated with right fronto-temporal regions, whereas left total memory scores correlated with left lateral and medial temporal regions. The findings indicate that (i) episodic memory is subserved by more widespread cortical regions beyond the core mesiotemporal lobe memory structures; (ii) there are different networks functional in the two hemispheres; and (iii) areas involved in memory may be different between patients with left and nonleft dominance for language, particularly in the right hemisphere.
The Attentional Blink Reveals Serial Working Memory Encoding: Evidence from Virtual and Human Event-related Potentials
Authors: Craston Patrick , Wyble Brad , Chennu Srivas , Bowman Howard 
Published: June 2008

Abstract
Observers often miss a second target (T2) if it follows an identified first target item (T1) within half a second in rapid serial visual presentation (RSVP), a finding termed the attentional blink. If two targets are presented in immediate succession, however, accuracy is excellent (Lag 1 sparing). The resource sharing hypothesis proposes a dynamic distribution of resources over a time span of up to 600 msec during the attentional blink. In contrast, the ST2 model argues that working memory encoding is serial during the attentional blink and that, due to joint consolidation, Lag 1 is the only case where resources are shared. Experiment 1 investigates the P3 ERP component evoked by targets in RSVP. The results suggest that, in this context, P3 amplitude is an indication of bottom–up strength rather than a measure of cognitive resource allocation. Experiment 2, employing a two-target paradigm, suggests that T1 consolidation is not affected by the presentation of T2 during the attentional blink. However, if targets are presented in immediate succession (Lag 1 sparing), they are jointly encoded into working memory. We use the ST2 model's neural network implementation, which replicates a range of behavioral results related to the attentional blink, to generate “virtual ERPs” by summing across activation traces. We compare virtual to human ERPs and show how the results suggest a serial nature of working memory encoding as implied by the ST2 model.
Retrieval from Episodic Memory: Neural Mechanisms of Interference Resolution
Authors: Wimber Maria , Rutschmann Roland Marcus , Greenlee Mark W. , Bäuml Karl-Heinz 
Published: June 2008

Abstract
Selectively retrieving a target memory among related memories requires some degree of inhibitory control over interfering and competing memories, a process assumed to be supported by inhibitory mechanisms. Evidence from behavioral studies suggests that such inhibitory control can lead to subsequent forgetting of the interfering information, a finding called retrieval-induced forgetting [Anderson, M. C., Bjork, R. A., & Bjork, E. L. Remembering can cause forgetting: Retrieval dynamics in long-term memory. Journal of Experimental Psychology: Learning, Memory & Cognition, 20, 1063–1087, 1994]. In the present functional magnetic resonance imaging study, we investigated the neural processes underlying retrieval-induced forgetting and, in particular, examined the extent to which these processes are retrieval (i.e., selection) specific. Participants actively retrieved a subset of previously studied material (selection condition), or were re-exposed to the same material for relearning (nonselection condition). Replicating prior behavioral work, selective retrieval caused significant forgetting of the nonretrieved items on a delayed recall test, relative to the re-exposure condition. Selective retrieval was associated with increased BOLD responses in the posterior temporal and parietal association cortices, in the bilateral hippocampus, and in the dorsolateral prefrontal cortex. Medial and lateral prefrontal areas showed a strong negative linear relationship between selection-related neural activity and subsequent forgetting of competitors. These findings suggest reduced demands on inhibitory control processes when interference is successfully resolved during early selective retrieval from episodic memory.
Cerebral White Matter Integrity Mediates Adult Age Differences in Cognitive Performance
Authors: Madden David J. , Spaniol Julia , Costello Matthew C. , Bucur Barbara , White Leonard E. , Cabeza Roberto , Davis Simon W. , Dennis Nancy A. , Provenzale James M. , Huettel Scott A. 
Published: June 2008

Abstract
Previous research has established that age-related decline occurs in measures of cerebral white matter integrity, but the role of this decline in age-related cognitive changes is not clear. To conclude that white matter integrity has a mediating (causal) contribution, it is necessary to demonstrate that statistical control of the white matter–cognition relation reduces the magnitude of age–cognition relation. In this research, we tested the mediating role of white matter integrity, in the context of a task-switching paradigm involving word categorization. Participants were 20 healthy, community-dwelling older adults (60–85 years), and 20 younger adults (18–27 years). From diffusion tensor imaging tractography, we obtained fractional anisotropy (FA) as an index of white matter integrity in the genu and splenium of the corpus callosum and the superior longitudinal fasciculus (SLF). Mean FA values exhibited age-related decline consistent with a decrease in white matter integrity. From a model of reaction time distributions, we obtained independent estimates of the decisional and nondecisional (perceptual–motor) components of task performance. Age-related decline was evident in both components. Critically, age differences in task performance were mediated by FA in two regions: the central portion of the genu, and splenium–parietal fibers in the right hemisphere. This relation held only for the decisional component and was not evident in the nondecisional component. This result is the first demonstration that the integrity of specific white matter tracts is a mediator of age-related changes in cognitive performance.
Grapheme–Color Synesthesia Influences Overt Visual Attention
Authors: Carriere Jonathan S. A. , Eaton Daniel , Reynolds Michael G. , Dixon Mike J. , Smilek Daniel 
Published: June 2008

Abstract
For individuals with grapheme–color synesthesia, achromatic letters and digits elicit vivid perceptual experiences of color. We report two experiments that evaluate whether synesthesia influences overt visual attention. In these experiments, two grapheme–color synesthetes viewed colored letters while their eye movements were monitored. Letters were presented in colors that were either congruent or incongruent with the synesthetes' colors. Eye tracking analysis showed that synesthetes exhibited a color congruity bias—a propensity to fixate congruently colored letters more often and for longer durations than incongruently colored letters—in a naturalistic free-viewing task. In a more structured visual search task, this congruity bias caused synesthetes to rapidly fixate and identify congruently colored target letters, but led to problems in identifying incongruently colored target letters. The results are discussed in terms of their implications for perception in synesthesia.
The Case of Pretense: Observing Actions and Inferring Goals
Authors: Schubotz Ricarda I. , von Cramon D. Yves 
Published: June 2008

AbstractWhen we observe an action, we know almost immediately what goal is pursued by the actor. Strikingly, this applies also to pretend action (pantomime), which provides relevant information about the manipulation itself but not about the manipulated objects. The present fMRI study addressed the issue of goal inference from pretend action as compared with real action. We found differences as well as commonalities for the brain correlates of inferring goals from both types of action. They differed with regard to the weights of the underlying action observation network, indicating the exploitation of object information in the case of real actions and manipulation information in the case of pretense. However, goal inferences from manipulation information resulted in a common network for both real and pretend action. Interestingly, this latter network also comprised areas that are not identified by action observation and that might be due to the processing of scene gist and to the evaluation of fit of putative action goals. These findings suggest that observation of pretense emphasizes the requirement to internally simulate the observed act but rule out fundamental differences of how observers cope with real and pretend action.