Expression of VEGF, HGF, IL-6, IL-8, MMP-9, Telomerase in Peripheral Blood of Patients with Head and Neck Squamous Cell Carcinoma

ObjectivesThis study investigated the telomerase expression in peripheral blood mononuclear cells (PBMCs) and the relationship between the serum level of several soluble factors such as vascular endothelial growth factor (VEGF), hepatocyte growth factor, interleukin (IL)-6, IL-8, and matrix metallopeptidase-9 and the clinicopathological features of patients with head and neck squamous cell carcinoma (HNSCC).MethodsPeripheral blood samples were collected from 50 HNSCC patients and 15 normal controls. The telomerase activity in the PBMCs was measured by Telomere Repeat Amplification Protocols. The serum levels of the soluble factors were analyzed by enzyme-linked immunosorbent assay.ResultsThe expression of telomerase in the PBMCs of HNSCC patients was significantly correlated with the N and American Joint Committee on Cancer (AJCC) stages. The serum VEGF level was significantly higher in the patients with an advanced T stage, N stage and AJCC stage. Serum VEGF was significantly related with the expression of telomerase in the PBMCs. The telomerase expression and the VEGF expression were shown to be independent factors associated with poor survival.ConclusionThe telomerase expression in the PBMCs and the serum VEGF level of HNSCC patients were significantly correlated with the N stage, the AJCC stage and the prognosis

Neural correlates of enhanced visual short-term memory for angry faces: An fMRI study

Copyright: © 2008 Jackson et al.Background: Fluid and effective social communication requires that both face identity and emotional expression information are encoded and maintained in visual short-term memory (VSTM) to enable a coherent, ongoing picture of the world and its players. This appears to be of particular evolutionary importance when confronted with potentially threatening displays of emotion - previous research has shown better VSTM for angry versus happy or neutral face identities.Methodology/Principal Findings: Using functional magnetic resonance imaging, here we investigated the neural correlates of this angry face benefit in VSTM. Participants were shown between one and four to-be-remembered angry, happy, or neutral faces, and after a short retention delay they stated whether a single probe face had been present or not in the previous display. All faces in any one display expressed the same emotion, and the task required memory for face identity. We find enhanced VSTM for angry face identities and describe the right hemisphere brain network underpinning this effect, which involves the globus pallidus, superior temporal sulcus, and frontal lobe. Increased activity in the globus pallidus was significantly correlated with the angry benefit in VSTM. Areas modulated by emotion were distinct from those modulated by memory load.Conclusions/Significance: Our results provide evidence for a key role of the basal ganglia as an interface between emotion and cognition, supported by a frontal, temporal, and occipital network.The authors were supported by a Wellcome Trust grant (grant number 077185/Z/05/Z) and by BBSRC (UK) grant BBS/B/16178

Repetition Suppression and Reactivation in Auditory–Verbal Short-Term Recognition Memory

The neural response to stimulus repetition is not uniform across brain regions, stimulus modalities, or task contexts. For instance, it has been observed in many functional magnetic resonance imaging (fMRI) studies that sometimes stimulus repetition leads to a relative reduction in neural activity (repetition suppression), whereas in other cases repetition results in a relative increase in activity (repetition enhancement). In the present study, we hypothesized that in the context of a verbal short-term recognition memory task, repetition-related “increases” should be observed in the same posterior temporal regions that have been previously associated with “persistent activity” in working memory rehearsal paradigms. We used fMRI and a continuous recognition memory paradigm with short lags to examine repetition effects in the posterior and anterior regions of the superior temporal cortex. Results showed that, consistent with our hypothesis, the 2 posterior temporal regions consistently associated with working memory maintenance, also show repetition increases during short-term recognition memory. In contrast, a region in the anterior superior temporal lobe showed repetition suppression effects, consistent with previous research work on perceptual adaptation in the auditory–verbal domain. We interpret these results in light of recent theories of the functional specialization along the anterior and posterior axes of the superior temporal lobe

Tristetraprolin regulates interleukin‐6, which is correlated with tumor progression in patients with head and neck squamous cell carcinoma

BACKGROUND: Tumor‐derived cytokines play a significant role in the progression of head and neck squamous cell carcinoma (HNSCC). Targeting proteins, such as tristetraprolin (TTP), that regulate multiple inflammatory cytokines may inhibit the progression of HNSCC. However, TTP's role in cancer is poorly understood. The goal of the current study was to determine whether TTP regulates inflammatory cytokines in patients with HNSCC. METHODS: TTP messenger RNA (mRNA) and protein expression were determined by quantitative real‐time–polymerase chain reaction (Q‐RT‐PCR) and Western blot analysis, respectively. mRNA stability and cytokine secretion were evaluated by quantitative RT‐PCR and enzyme‐linked immunoadsorbent assay, respectively, after overexpression or knockdown of TTP in HNSCC. HNSCC tissue microarrays were immunostained for interleukin‐6 (IL‐6) and TTP. RESULTS: TTP expression in HNSCC cell lines was found to be inversely correlated with the secretion of IL‐6, vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE 2 ) . Knockdown of TTP increased mRNA stability and the secretion of cytokines. Conversely, overexpression of TTP in HNSCC cells led to decreased secretion of IL‐6, VEGF, and PGE 2 . Immunohistochemical staining of tissue microarrays for IL‐6 demonstrated that staining intensity is prognostic for poor disease‐specific survival ( P = .023), tumor recurrence and development of second primary tumors ( P = .014), and poor overall survival ( P = .019). CONCLUSIONS: The results of the current study demonstrated that down‐regulation of TTP in HNSCC enhances mRNA stability and promotes secretion of IL‐6, VEGF, and PGE 2 . Furthermore, high IL‐6 secretion in HNSCC tissue is a biomarker for poor prognosis. In as much as enhanced cytokine secretion is associated with poor prognosis, TTP may be a therapeutic target to reduce multiple cytokines concurrently in patients with HNSCC. Cancer 2011. © 2011 American Cancer Society. Tristetraprolin (TTP), a protein that decreases the stability of messenger RNA (mRNA) of cytokines and proinflammatory factors, is reduced in patients with head and neck squamous cell carcinoma with a corresponding increase in interleukin‐6 (IL‐6), vascular endothelial growth factor, and cyclooxygenase‐2 secretion. One of these tumor‐derived cytokines, IL‐6, is prognostic for poor disease‐specific survival, tumor recurrence, second primary lesions, and poor overall survival.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86915/1/25859_ftp.pd

Modulating perceptual complexity and load reveals degradation of the visual working memory network in ageing

Previous neuroimaging studies have reported a posterior to anterior shift of activation in ageing (PASA). Here, we explore the nature of this shift by modulating load (1,2 or 3 items) and perceptual complexity in two variants of a visual working memory task (VWM): a ‘simple’ color and a ‘complex’ shape change detection task. Functional near-infrared spectroscopy (fNIRS) was used to record changes in activation in younger (N=24) and older adults (N=24). Older adults exhibited PASA by showing lesser activation in the posterior cortex and greater activation in the anterior cortex when compared to younger adults. Further, they showed reduced accuracy at loads 2 and 3 for the simple task and across all loads for the complex task. Activation in the posterior and anterior cortices was modulated differently for younger and older adults. In older adults, increasing load in the simple task was accompanied by decreasing activation in the posterior cortex and lack of modulation in the anterior cortex, suggesting the inability to encode and/or maintain representations without much aid from higher-order centers. In the complex task, older adults recruited verbal working memory areas in the posterior cortex, suggesting that they used adaptive strategies such as labelling the shape stimuli. This was accompanied by reduced activation in the anterior cortex reflecting the inability to exert top-down modulation to typical VWM areas in the posterior cortex to improve behavioral performance

Validating an image-based fNIRS approach with fMRI and a working memory task

In the current study, we extend a previous methodological pipeline by adding a novel image reconstruction approach to move functional near-infrared (fNIRS) signals from channel-space on the surface of the head to voxel-space within the brain volume. We validate this methodology by comparing voxel-wise fNIRS results to functional magnetic resonance imaging (fMRI) results from a visual working memory (VWM) task using two approaches. In the first approach, significant voxel-wise correlations were observed between fNIRS and fMRI measures for all experimental conditions across brain regions in the fronto-parieto-temporal cortices. In the second approach, we conducted separate multi-factorial ANOVAs on fNIRS and fMRI measures and then examined the correspondence between main and interaction effects within common regions of interest. Both fMRI and fNIRS showed similar trends in activation within the VWM network when the number of items held in working memory increases. These results validate the image-based fNIRS approach

How Are ‘Barack Obama’ and ‘President Elect’ Differentially Stored in the Brain? An ERP Investigation on the Processing of Proper and Common Noun Pairs

BACKGROUND:One of the most debated issues in the cognitive neuroscience of language is whether distinct semantic domains are differentially represented in the brain. Clinical studies described several anomic dissociations with no clear neuroanatomical correlate. Neuroimaging studies have shown that memory retrieval is more demanding for proper than common nouns in that the former are purely arbitrary referential expressions. In this study a semantic relatedness paradigm was devised to investigate neural processing of proper and common nouns. METHODOLOGY/PRINCIPAL FINDINGS:780 words (arranged in pairs of Italian nouns/adjectives and the first/last names of well known persons) were presented. Half pairs were semantically related ("Woody Allen" or "social security"), while the others were not ("Sigmund Parodi" or "judicial cream"). All items were balanced for length, frequency, familiarity and semantic relatedness. Participants were to decide about the semantic relatedness of the two items in a pair. RTs and N400 data suggest that the task was more demanding for common nouns. The LORETA neural generators for the related-unrelated contrast (for proper names) included the left fusiform gyrus, right medial temporal gyrus, limbic and parahippocampal regions, inferior parietal and inferior frontal areas, which are thought to be involved in the conjoined processing a familiar face with the relevant episodic information. Person name was more emotional and sensory vivid than common noun semantic access. CONCLUSIONS/SIGNIFICANCE:When memory retrieval is not required, proper name access (conspecifics knowledge) is not more demanding. The neural generators of N400 to unrelated items (unknown persons and things) did not differ as a function of lexical class, thus suggesting that proper and common nouns are not treated differently as belonging to different grammatical classes

Dissociated Mechanisms of Extracting Perceptual Information into Visual Working Memory

The processing mechanisms of visual working memory (VWM) have been extensively explored in the recent decade. However, how the perceptual information is extracted into VWM remains largely unclear. The current study investigated this issue by testing whether the perceptual information was extracted into VWM via an integrated-object manner so that all the irrelevant information would be extracted (object hypothesis), or via a feature-based manner so that only the target-relevant information would be extracted (feature hypothesis), or via an analogous processing manner as that in visual perception (analogy hypothesis).High-discriminable information which is processed at the parallel stage of visual perception and fine-grained information which is processed via focal attention were selected as the representatives of perceptual information. The analogy hypothesis predicted that whereas high-discriminable information is extracted into VWM automatically, fine-grained information will be extracted only if it is task-relevant. By manipulating the information type of the irrelevant dimension in a change-detection task, we found that the performance was affected and the ERP component N270 was enhanced if a change between the probe and the memorized stimulus consisted of irrelevant high-discriminable information, but not if it consisted of irrelevant fine-grained information.We conclude that dissociated extraction mechanisms exist in VWM for information resolved via dissociated processes in visual perception (at least for the information tested in the current study), supporting the analogy hypothesis