bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radioimmunotherapy with α-Particle–Emitting 213Bi-C-Functionalized trans-Cyclohexyl-Diethylenetriaminepentaacetic Acid-Humanized 3S193 Is Enhanced by Combination with Paclitaxel Chemotherapy
Authors: Kelly Marcus P. , Lee Fook T. , Tahtis Kiki , Smyth Fiona E. , Brechbiel Martin W. , Scott Andrew M. 
Published: September 2007

Abstract
Purpose: Previous experience in solid tumor radioimmunotherapy studies has indicated that greatest therapeutic efficacy is achieved in the treatment of small-volume disease. α-Particle–emitting radioisotopes possess several physical characteristics ideally suited to the treatment of minimal residual disease. Therefore, we have investigated the efficacy of the α-particle–emitting bismuth-213 (213Bi) radioimmunotherapy using the humanized anti-Lewis Y (Ley) monoclonal antibody humanized 3S193 (hu3S193).
Experimental Design: The intracellular localization of hu3S193 in Ley-positive MCF-7 breast carcinoma cells was assessed by confocal microscopy. Cytotoxicity of 213Bi-hu3S193 and apoptosis was assessed using [3H]thymidine incorporation assay and ELISA, respectively. Immunoblotting for γ-H2AX assessed DNA strand breaks. In vivo efficacy of 213Bi-hu3S193 was assessed using a minimal residual disease model in BALB/c nude mice, with radioconjugate [15, 30, and 60 μCi (9.2 μg)] injected 2 days after s.c. implantation of MCF-7 cells. Radioimmunotherapy was also combined with a single injection of 300 μg paclitaxel to explore improved efficacy. Further, mice with established tumors received 30, 60, or 120 μCi (14.5 μg) of 213Bi-hu3S193 to assess the effect of tumor volume on treatment efficacy.
Results: hu3S193 is internalized via an endosomal and lysosomal trafficking pathway. Treatment with 213Bi-hu3S193 results in &gt;90% cytotoxicity in vitro and induces apoptosis and increased γ-H2AX expression. 213Bi-hu3S193 causes specific and significant retardation of tumor growth even in established tumors, and efficacy was enhanced by paclitaxel to produce defined complete responses.
Conclusions: These studies show the potency of α-particle radioimmunotherapy and warrant its further exploration in the treatment of micrometastatic disease in Ley-positive malignancies.
Toll-like Receptors in Tumor Immunotherapy
Authors: Paulos Chrystal M. , Kaiser Andrew , Wrzesinski Claudia , Hinrichs Christian S. , Cassard Lydie , Boni Andrea , Muranski Pawel , Sanchez-Perez Luis , Palmer Douglas C. , Yu Zhiya , Antony Paul A. , Gattinoni Luca , Rosenberg Steven A. , Restifo Nicholas P. 
Published: September 2007

AbstractLymphodepletion with chemotherapeutic agents or total body irradiation (TBI) before adoptive transfer of tumor-specific T cells is a critical advancement in the treatment of patients with melanoma. More than 50% of patients that are refractory to other treatments experience an objective or curative response with this approach. Emerging data indicate that the key mechanisms underlying how TBI augments the functions of adoptively transferred T cells include (a) the depletion of regulatory T cells (Treg) and myeloid-derived suppressor cells that limit the function and proliferation of adoptively transferred cells; (b) the removal of immune cells that act as “sinks” for homeostatic cytokines, whose levels increase after lymphodepletion; and (c) the activation of the innate immune system via Toll-like receptor 4 signaling, which is engaged by microbial lipopolysaccharide that translocated across the radiation-injured gut. Here, we review these mechanisms and focus on the effect of Toll-like receptor agonists in adoptive immunotherapy. We also discuss alternate regimens to chemotherapy or TBI, which might be used to safely treat patients with advanced disease and promote tumor regression.
Reactive oxygen species mediated apoptosis of esophageal cancer cells induced by marine triprenyl toluquinones and toluhydroquinones
Authors: Whibley Catherine E. , McPhail Kerry L. , Keyzers Robert A. , Maritz Michelle F. , Leaner Virna D. , Birrer Michael J. , Davies-Coleman Michael T. , Hendricks Denver T. 
Published: September 2007

Abstract
Marine invertebrates, algae, and microorganisms are prolific producers of novel secondary metabolites. Some of these secondary metabolites have the potential to be developed as chemotherapeutic agents for the treatment of a wide variety of diseases, including cancer. We describe here the mechanism leading to apoptosis of esophageal cancer cell lines in the presence of triprenylated toluquinones and toluhydroquinones originally isolated from the Arminacean nudibranch Leminda millecra. Triprenylated toluquinone–induced and toluhydroquinone-induced cell death is mediated via apoptosis after a cell cycle block. Molecular events include production of reactive oxygen species (ROS), followed by induction and activation of c-Jun (AP1) via c-Jun-NH2-kinase–mediated and extracellular signal-regulated kinase–mediated pathways. Partial resistance to these compounds could be conferred by the ROS scavengers Trolox and butylated hydroxyanisol, a c-Jun-NH2-kinase inhibitor, and inhibition of c-Jun with a dominant negative mutant (TAM67). Interestingly, the levels of ROS produced varied between compounds, but was proportional to the ability of each compound to kill cells. Because cancer cells are often more susceptible to ROS, these compounds present a plausible lead for new antiesophageal cancer treatments and show the potential of the South African marine environment to provide new chemical entities with potential clinical significance. [Mol Cancer Ther 2007;6(9):2535–43]
Quercetin enhances TRAIL-mediated apoptosis in colon cancer cells by inducing the accumulation of death receptors in lipid rafts
Authors: Psahoulia Faiy H. , Drosopoulos Konstantinos G. , Doubravska Lenka , Andera Ladislav , Pintzas Alexander 
Published: September 2007

Abstract
Cytokines such as tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) can induce apoptosis in colon cancer cells through engagement of death receptors. Nevertheless, evading apoptosis induced by anticancer drugs characterizes many types of cancers. This results in the need for combination therapy. In this study, we have investigated whether the flavonoid quercetin could sensitize human colon adenocarcinoma cell lines to TRAIL-induced apoptosis. We report that quercetin enhanced TRAIL-induced apoptosis by causing the redistribution of DR4 and DR5 into lipid rafts. Nystatin, a cholesterol-sequestering agent, prevented quercetin-induced clustering of death receptors and sensitization to TRAIL-induced apoptosis in colon adenocarcinoma cells. In addition, our experiments show that quercetin, in combination with TRAIL, triggered the mitochondrial-dependent death pathway, as shown by Bid cleavage and the release of cytochrome c to the cytosol. Together, our findings propose that quercetin, through its ability to redistribute death receptors at the cell surface, facilitates death-inducing signaling complex formation and activation of caspases in response to death receptor stimulation. Based on these results, this study provides a challenging approach to enhance the efficiency of TRAIL-based therapies. [Mol Cancer Ther 2007;6(9):2591–9]
Thiothymidine plus low-dose UVA kills hyperproliferative human skin cells independently of their human papilloma virus status
Authors: Reelfs Olivier , Xu Yao-Zhong , Massey Andrew , Karran Peter , Storey Alan 
Published: September 2007

Abstract
The thymidine analogue 4-thiothymidine (S4TdR) is a photosensitizer for UVA radiation. The UV absorbance spectrum of S4TdR and its incorporation into DNA suggests that it might act synergistically with nonlethal doses of UVA to selectively kill hyperproliferative or cancerous skin cells. We show here that nontoxic concentrations of S4TdR combine with nonlethal doses of UVA to kill proliferating cultured skin cells. Established cell lines with a high fraction of proliferating cells were more sensitive than primary keratinocytes or fibroblasts to apoptosis induction by S4TdR/UVA. Although S4TdR plus UVA treatment induces stabilization of p53, cell death, as measured by apoptosis or clonal survival, occurs to a similar extent in both p53 wild-type and p53-null backgrounds. Furthermore, different types of human papilloma virus E6 proteins, which protect against UVB-induced apoptosis, have little effect on killing by S4TdR/UVA. S4TdR/UVA offers a possible therapeutic intervention strategy that seems to be applicable to human papilloma virus–associated skin lesions. [Mol Cancer Ther 2007;6(9):2487–95]
Sox10 Has a Broad Expression Pattern in Gliomas and Enhances Platelet-Derived Growth Factor-B–Induced Gliomagenesis
Authors: Ferletta Maria , Uhrbom Lene , Olofsson Tommie , Pontén Fredrik , Westermark Bengt 
Published: September 2007

Abstract
In a previously published insertional mutagenesis screen for candidate brain tumor genes in the mouse using a Moloney mouse leukemia virus encoding platelet-derived growth factor (PDGF)-B, the Sox10 gene was tagged in five independent tumors. The proviral integrations suggest an enhancer effect on Sox10. All Moloney murine leukemia virus/PDGFB tumors had a high protein expression of Sox10 independently of malignant grade or tumor type. To investigate the role of Sox10 in gliomagenesis, we used the RCAS/tv-a mouse model in which the expression of retroviral-encoded genes can be directed to glial progenitor cells (Ntv-a mice). Both Ntv-a transgenic mice, wild-type, and Ntv-a p19Arf null mice were injected with RCAS-SOX10 alone or in combination with RCAS-PDGFB. Infection with RCAS-SOX10 alone did not induce any gliomas. Combined infection of RCAS-SOX10 and RCAS-PDGFB in wild-type Ntv-a mice yielded a tumor frequency of 12%, and in Ntv-a Arf−/− mice the tumor frequency was 30%. This indicates that Sox10 alone is not sufficient to induce gliomagenesis but acts synergistically with PDGFB in glioma development. All induced tumors displayed characteristics of PNET-like structures and oligodendroglioma. The tumors had a strong and widely distributed expression of Sox10 and PDGFR-α. We investigated the expression of Sox10 in other human tumors and in a number of gliomas. The Sox10 expression was restricted to gliomas and melanomas. All glioma types expressed Sox10, and tumors of low-grade glioma had a much broader distribution of Sox10 compared with high-grade gliomas. (Mol Cancer Res 2007;5(9):891–7)
Taxi vs. Taksi: On Orthographic Word Recognition in the Left Ventral Occipitotemporal Cortex
Authors: Kronbichler Martin , Bergmann Jürgen , Hutzler Florian , Staffen Wolfgang , Mair Alois , Ladurner Gunther , Wimmer Heinz 
Published: September 2007

Abstract
The importance of the left occipitotemporal cortex for visual word processing is highlighted by numerous functional neuroimaging studies, but the precise function of the visual word form area (VWFA) in this brain region is still under debate. The present functional magnetic resonance imaging study varied orthographic familiarity independent from phonological-semantic familiarity by presenting orthographically familiar and orthographically unfamiliar forms (pseudohomophones) of the same words in a phonological lexical decision task. Consistent with orthographic word recognition in the VWFA, we found lower activation for familiar compared with unfamiliar forms, but no difference between pseudohomophones and pseudowords. This orthographic familiarity effect in the VWFA differed from the phonological familiarity effect in left frontal regions, where phonologically unfamiliar pseudowords led to higher activation than phonologically familiar pseudohomophones. We suggest that the VWFA not only computes letter string representations but also hosts word-specific orthographic representations. These representations function as recognition units with the effect that letter strings that readily match with stored representations lead to less activation than letter strings that do not.
Functional Neural Networks of Semantic and Syntactic Processes in the Developing Brain
Authors: Brauer Jens , Friederici Angela D. 
Published: September 2007

Abstract
The functional neuroanatomy of language in the adult brain separates semantic and syntactic processes in the superior temporal gyrus (STG) and in the inferior frontal cortex. It is unknown whether a similar specialization is present in the developing brain. Semantic and syntactic aspects of sentence processing were investigated in 5- to 6-year-old children and in adults using functional magnetic resonance imaging. Although adults demonstrated function-specific activations in the STG and the frontal operculum, children showed a large activation overlap for these two language aspects in the STG. Compared to adults, they engaged additional areas in the left and right inferior frontal gyrus, which are known to support resource demanding processes. Thus, the language networks for semantic and syntactic processes are not yet specialized similarly to adults in the developing brain.
Preattentive Sensory Processing as Indexed by the MMN and P3a Brain Responses is Associated with Cognitive and Psychosocial Functioning in Healthy Adults
Authors: Light Gregory A. , Swerdlow Neal R. , Braff David L. 
Published: September 2007

AbstractUnderstanding the basic neural processes that underlie complex higher order cognitive operations and psychosocial functioning is a fundamental goal of cognitive neuroscience. Event-related potentials allow investigators to probe the earliest stages of information processing. Mismatch negativity (MMN) and P3a are auditory event-related potential components that reflect automatic sensory discrimination. The aim of the present study was to determine if MMN and P3a are associated with higher order cognitive operations and psychosocial functioning in clinically normal healthy subjects. Twenty adults were assessed using standardized clinical, cognitive, and psychosocial functional instruments. All individuals were within the normal range on cognitive tests and functional ratings. Participants were also tested on a duration-deviant MMN/P3a paradigm (50-msec standard tones, p = .90; 100-msec deviant tones, p = .10; stimulus onset asynchrony [SOA] = 505 msec). Across fronto-central electrode regions, significant correlations were observed between psychosocial functioning and MMN (r = −.62, p &lt; .01) and P3a (r = .63, p &lt; .01) amplitudes. P3a amplitude was also highly associated with immediate and delayed recall of verbal information with robust correlations widely distributed across fronto-central recording areas (e.g., r = .72, p &lt; .001). The latency of the P3a response was significantly associated with both working memory performance (r = −.53, p &lt; .05) and functional ratings (r = −.48, p &lt; .05). Neurophysiological measures of relatively automatic auditory sensory information processing are associated with higher order cognitive abilities and psychosocial functioning in normal subjects. Efficiency at elementary levels of information processing may underlie the successful encoding, retrieval, and discrimination of task-relevant information, which, in turn, facilitates the iterative and responsive processing necessary for adaptive cognitive and social functioning.
The What and How of Observational Learning
Authors: Torriero Sara , Oliveri Massimiliano , Koch Giacomo , Caltagirone Carlo , Petrosini Laura 
Published: September 2007

Abstract
Neuroimaging evidence increasingly supports the hypothesis that the same neural structures subserve the execution, imagination, and observation of actions. We used repetitive transcranial magnetic stimulation (rTMS) to investigate the specific roles of cerebellum and dorsolateral prefrontal cortex (DLPFC) in observational learning of a visuomotor task. Subjects observed an actor detecting a hidden sequence in a matrix and then performed the task detecting either the previously observed sequence or a new one. rTMS applied over the cerebellum before the observational training interfered with performance of the new sequence, whereas rTMS applied over the DLPFC interfered with performance of the previously observed one. When rTMS applied over cerebellar or prefrontal site was delivered after the observational training, no influence was observed on the execution of the task. These results furnish new insights on the neural circuitry involved in the single component of observational learning and allow us to hypothesize that cerebellum and DLPFC interact in planning actions, the former by permitting the acquisition of procedural competencies and the latter by providing flexibility among already acquired solutions.
Regularity Extraction and Application in Dynamic Auditory Stimulus Sequences
Authors: Bendixen Alexandra , Roeber Urte , Schröger Erich 
Published: September 2007

Abstract
Traditional auditory oddball paradigms imply the brain's ability to encode regularities, but are not optimal for investigating the process of regularity establishment. In the present study, a dynamic experimental protocol was developed that simulates a more realistic auditory environment with changing regularities. The dynamic sequences were included in a distraction paradigm in order to study regularity extraction and application. Subjects discriminated the duration of sequentially presented tones. Without relevance to the task, tones repeated or changed in frequency according to a pattern unknown to the subject. When frequency repetitions were broken by a deviating tone, behavioral distraction (prolonged reaction time in the duration discrimination task) was elicited. Moreover, event-related brain potential components indicated deviance detection (mismatch negativity), involuntary attention switches (P3a), and attentional reorientation. These results suggest that regularities were extracted from the dynamic stimulation and were used to predict forthcoming stimuli. The effects were already observed with deviants occurring after as few as two presentations of a standard frequency, that is, violating a just emerging rule. Effects of regularity violation strengthened with the number of standard repetitions. Control stimuli comprising no regularity revealed that the observed effects were due to both improvements in standard processing (benefits of regularity establishment) and deteriorations in deviant processing (costs of regularity violation). Thus, regularities are exploited in two different ways: for an efficient processing of regularity-conforming events as well as for the detection of nonconforming, presumably important events. The present results underline the brain's flexibility in its adaptation to environmental demands.
Neglected Time: Impaired Temporal Perception of Multisecond Intervals in Unilateral Neglect
Authors: Danckert James , Ferber Susanne , Pun Carson , Broderick Carol , Striemer Christopher , Rock Sherry , Stewart Dwight 
Published: September 2007

AbstractRecent neuroimaging and neuropsychological studies have suggested that the right hemisphere, particularly frontal regions, is important for the perception of the passage of time. We examined the ability to estimate durations of up to 60 sec in a group of eight patients with unilateral neglect. When estimating multisecond intervals, neglect patients grossly underestimated all durations. On average, healthy controls (HC) demonstrated reasonably accurate estimates of all durations tested. Although the right hemisphere lesioned control patients without neglect also tended to underestimate durations, these underestimations were significantly better than the performance of the neglect group. These findings suggest a pivotal role for a right hemisphere fronto-parietal network in the accurate perception of multisecond durations. Furthermore, these findings add to a growing body of literature suggesting that neglect cannot be understood simply in terms of a bias in orienting attention to one side of space. Additional deficits of the kind demonstrated here are likely to be crucial in determining the nature and extent of the loss of conscious awareness for contralesional events.
Feature- and Object-based Attentional Modulation in the Human Auditory “Where” Pathway
Authors: Krumbholz Katrin , Eickhoff Simon B. , Fink Gereon R. 
Published: September 2007

Abstract
Attending to a visual stimulus feature, such as color or motion, enhances the processing of that feature in the visual cortex. Moreover, the processing of the attended object's other, unattended, features is also enhanced. Here, we used functional magnetic resonance imaging to show that attentional modulation in the auditory system may also exhibit such feature- and object-specific effects. Specifically, we found that attending to auditory motion increases activity in nonprimary motion-sensitive areas of the auditory cortical “where” pathway. Moreover, activity in these motion-sensitive areas was also increased when attention was directed to a moving rather than a stationary sound object, even when motion was not the attended feature. An analysis of effective connectivity revealed that the motion-specific attentional modulation was brought about by an increase in connectivity between the primary auditory cortex and nonprimary motion-sensitive areas, which, in turn, may have been mediated by the paracingulate cortex in the frontal lobe. The current results indicate that auditory attention can select both objects and features. The finding of feature-based attentional modulation implies that attending to one feature of a sound object does not necessarily entail an exhaustive processing of the object's unattended features.
Human Factors for Enhancing Live Video Streams with Virtual Reality: Performance, Situation Awareness, and Feeling of Telepresence
Authors: Pongrac Helena , Leupold Jan , Behrendt Stephan , Färber Berthold , Färber Georg 
Published: September 2007

Telepresence systems should be designed to assist the human operator as much as possible to fulfill his task. In order to support the user concerning the visual modality, a system was designed that presents virtual reality images combined together with camera images captured at the remote teleoperator environment.In this work, two experiments were conducted. In the first, it was shown that presenting a widened field of view to the human operator enhances the human performance and the feeling of telepresence. In the second, it was examined how the transition between video and virtual views has to be designed. Relevant criteria of this transition were chosen and the results show that the operator's rating of quality, feeling of telepresence, and situation awareness are positively affected by variations of the transition parameters. Furthermore, a trade-off between the rating of quality and the situation awareness was observed.A parameter selection scheme is presented which can serve as a design guideline for combining video and virtual views depending on the desired application.