bluuebunny/crossref_metadata_2025_split huggingface dataset:
A double dissociation between striate and extrastriate visual cortex for pattern motion perception revealed using rTMS
Authors: Thompson Benjamin , Aaen‐Stockdale Craig , Koski Lisa , Hess Robert F. 
Published: February 2009

AbstractThe neural mechanisms underlying the integration and segregation of motion signals are often studied using plaid stimuli. These stimuli consist of two spatially coincident dynamic gratings of differing orientations, which are either perceived to move in two unique directions or are integrated by the visual system to elicit the percept of a checkerboard moving in a single direction. Computations pertaining to the motion of the individual component gratings are thought to take place in striate cortex (V1) whereas motion integration is thought to involve neurons in dorsal stream extrastriate visual areas, particularly V5/MT. By combining a psychophysical task that employed plaid stimuli with 1 Hz offline repetitive transcranial magnetic stimulation (rTMS), we demonstrated a double dissociation between striate and extrastriate visual cortex in terms of their contributions to motion integration. rTMS over striate cortex increased coherent motion percepts whereas rTMS over extrastriate cortex had the opposite effect. These effects were robust directly after the stimulation administration and gradually returned to baseline within 15 minutes. This double dissociation is consistent with previous patient data and the recent hypothesis that both coherent and transparent motion percepts are supported by the visual system simultaneously and compete for perceptual dominance. Hum Brain Mapp 2009. © 2009 Wiley‐Liss, Inc.
An integrated humoral and cellular response is elicited in pancreatic cancer by α‐enolase, a novel pancreatic ductal adenocarcinoma‐associated antigen
Authors: Cappello Paola , Tomaino Barbara , Chiarle Roberto , Ceruti Patrizia , Novarino Anna , Castagnoli Carlotta , Migliorini Paola , Perconti Giovanni , Giallongo Agata , Milella Michele , Monsurrò Vladia , Barbi Stefano , Scarpa Aldo , Nisticò Paola , Giovarelli Mirella , Novelli Francesco 
Published: February 2009

AbstractPancreatic ductal adenocarcinoma (PDAC) is a fatal disease with a very poor 5‐year survival rate. α‐Enolase is a glycolytic enzyme that also acts as a surface plasminogen receptor. We find that it is overexpressed in PDAC and present on the cell surface of PDAC cell lines. The clinical correlation of its expression with tumor status has been reported for lung and hepatocellular carcinoma. We have previously demonstrated that sera from PDAC patients contain IgG autoantibodies to α‐enolase. The present work was intended to assess the ability of α‐enolase to induce antigen‐specific T cell responses. We show that α‐enolase‐pulsed dendritic cells (DC) specifically stimulate healthy autologous T cells to proliferate, secrete IFN‐γ and lyse PDAC cells but not normal cells. In vivo, α‐enolase‐specific T cells inhibited the growth of PDAC cells in immunodeficient mice. In 8 out of 12 PDAC patients with circulating IgG to α‐enolase, the existence of α‐enolase‐specific T cells was also demonstrated. Taken as a whole, these results indicate that α‐enolase elicits a PDAC‐specific, integrated humoral and cellular response. It is thus a promising and clinically relevant molecular target candidate for immunotherapeutic approaches as new adjuvants to conventional treatments in pancreatic cancer. © 2009 UICC
Genetic modulation of ADH1B and ALDH2 polymorphisms with regard to alcohol and tobacco consumption for younger aged esophageal squamous cell carcinoma diagnosis
Authors: Lee Chien‐Hung , Wu Deng‐Chyang , Wu I‐Chen , Goan Yih‐Gang , Lee Jang‐Ming , Chou Shah‐Hwa , Chan Te‐Fu , Huang Hsiao‐Ling , Hung Yu‐Hsiu , Huang Meng‐Chuan , Lai Tai‐Cheng , Wang Tsu‐Nai , Lan Cheng‐Che E. , Tsai Sharon , Lin Wen‐Yi , Wu Ming‐Tsang 
Published: February 2009

AbstractGenetic variants in alcohol dehydrogenase‐1B (ADH1B) and aldehyde dehydrogenase‐2 (ALDH2) genes modulate acetaldehyde removal upon alcohol ingestion. Although these genetic vulnerabilities have been linked to higher esophageal squamous cell carcinoma (ESCC) risks, it is unclear whether they also determine the time of malignancy presentation. The purpose of this investigation was to unravel genotoxic effects of the two alcohol‐metabolizing genes with regard to alcohol and tobacco consumption on the age at ESCC diagnosis and tumor dissemination. ADH1B/ALDH2 genotyping was performed on lymphocyte DNA specimens taken from 406 consecutively registered incident patients with pathology‐proven ESCC. To fully utilize individual genetic and survival information, survival analyses and gene‐longevity applied approaches were introduced. Among heavy drinkers, the ADH1B Arg/Arg (55 years) and ALDH2 Glu/Lys genotypes (54 years) were found to confer a 15 and 16 years earlier carcinoma diagnosed age than His/His and Glu/Glu nondrinkers (both 70 years), respectively. For drinkers, 1‐year age advancement was, separately, associated with a 0.977 and 0.953‐fold stepwise reduced likelihood of being ADH1B Arg homozygote and ALDH2 Lys variant. Noticeably elevated hazard‐ratio (HR) for drinkers of ADH1B slow‐form genotype and ALDH2 inactive‐form allele were identified in smokers (HR = 2.3–2.6), but no in nonsmokers. In smokers, appreciably higher cumulative cancer onset risks were correspondingly recognized from the age of 45 and 49 upward among any + Lys allele and Arg/Arg + Glu/Glu combined‐ADH1B/ALDH2‐genotype drinkers than nondrinkers. In conclusion, consumption of tobacco and alcohol, coupled with genetic susceptibilities associated with acetaldehyde elimination, as modulated by ADH1B and ALDH2 genotypes, determines a substantial magnitude of tumorigenetic effect on earlier age ESCC diagnosis. © 2009 UICC
Targeted therapy of renal cell carcinoma: Synergistic activity of cG250‐TNF and IFNg
Authors: Bauer Stefan , Oosterwijk‐Wakka Jeannette C. , Adrian Nicole , Oosterwijk Egbert , Fischer Eliane , Wüest Thomas , Stenner Frank , Perani Angelo , Cohen Leonard , Knuth Alexander , Divgi Chaitanya , Jäger Dirk , Scott Andrew M. , Ritter Gerd , Old Lloyd J. , Renner Christoph 
Published: February 2009

AbstractImmunotherapeutic targeting of G250/Carbonic anhydrase IX (CA‐IX) represents a promising strategy for treatment of renal cell carcinoma (RCC). The well characterized human‐mouse chimeric G250 (cG250) antibody has been shown in human studies to specifically enrich in CA‐IX positive tumors and was chosen as a carrier for site specific delivery of TNF in form of our IgG‐TNF‐fusion protein (cG250‐TNF) to RCC xenografts. Genetically engineered TNF constructs were designed as CH2/CH3 truncated cG250‐TNF fusion proteins and eucariotic expression was optimized under serum‐free conditions. In‐vitro characterization of cG250‐TNF comprised biochemical analysis and bioactivity assays, alone and in combination with Interferon‐γ (IFNγ). Biodistribution data on radiolabeled [125J] cG250‐TNF and antitumor activity of cG250‐TNF, alone and in combination with IFNγ, were measured on RCC xenografts in BALB/c nu/nu mice. Combined administration of cG250‐TNF and IFNγ caused synergistic biological effects that represent key mechanisms displaying antitumor responses. Biodistribution studies demonstrated specific accumulation and retention of cG250‐TNF at CA‐IX‐positive RCC resulting in growth inhibition of RCC and improved progression free survival and overall survival. Antitumor activity induced by targeted TNF‐based constructs could be enhanced by coadministration of low doses of nontargeted IFNγ without significant increase in side effects. Administration of cG250‐TNF and IFNγ resulted in significant synergistic tumoricidal activity. Considering the poor outcome of renal cancer patients with advanced disease, cG250‐TNF‐based immunotherapeutic approaches warrant clinical evaluation. © 2009 UICC
RNAi targeting urokinase‐type plasminogen activator receptor inhibits metastasis and progression of oral squamous cell carcinoma in vivo
Authors: Zhou Hao , Tang Yaling , Liang Xinhua , Yang Xiaoqin , Yang Jing , Zhu Guiquan , Zheng Min , Zhang Chunxu 
Published: February 2009

AbstractIt has been admitted that urokinase‐type plasminogen activator receptor (u‐PAR) is overexpressed in many human malignant tumors including oral squamous cell carcinoma (OSCC) and plays an important role in a variety of cancer key cellular events as a versatile signaling orchestrator. In our study, a retroviral vector expressing u‐PAR‐specific siRNA was injected into OSCC xenografts of nude mice to observe its inhibitory effects on OSCC. Our data demonstrate that siRNA targeting u‐PAR markedly suppressed tumor growth, reduced the expression of proliferation‐related gene, Ki‐67 and increased cell apoptosis, accompanying with the efficient and specific inhibition of endogenous u‐PAR expression in OSCC. More importantly, the mRNA and protein expression of MMP‐2, MMP‐9, VEGF‐C, VEGF‐D and VEGFR‐3 that are intimately involved in oral cancer invasion and metastasis, was simultaneously downregulated significantly as determined by quantitative real‐time RT‐PCR, Western blot and immunohistochemistry; and Gelatin and fibrin zymography showed that MMP‐9, MMP‐2 and u‐PA enzymatic activities were significantly reduced in u‐PAR‐specific siRNA group, compared to those in control groups. In addition, the expression of MDR‐1 gene related to drug resistance was obviously inhibited by silencing of u‐PAR. These findings suggest that RNAi targeting u‐PAR could effectively inhibit the metastasis and progression of OSCC in vivo. Thus, it may be used as a potent and specific therapy for oral cancer, especially in inhibiting and preventing cancer cell invasion and metastasis. © 2009 UICC
Vaccination with xenogeneic tumor endothelial proteins isolated in situ inhibits tumor angiogenesis and spontaneous metastasis
Authors: Zhang Wang , Liu Jian‐Ning , Tan Xiang‐Yang 
Published: February 2009

AbstractAngiogenesis is critical for tumor growth and metastasis. Tumor tissues induce the expression of angiogenesis‐associated proteins on endothelial surface that can be targeted for tumor immunotherapy. In our study, the rat tumor endothelial proteins (EP) were isolated in situ via biotinylation of tumor vascular endothelial luminal surface followed by streptavidin affinity chromatography. The isolated tumor EP contained numerous up‐regulated angiogenesis‐associated endothelial proteins. The administration of these tumor EP as a vaccine to mice reduced the microvessel density in subcutaneous primary LLC tumors, delayed spontaneous LLC tumor metastasis and prolonged post‐surgery life span. T lymphocytes from tumor EP‐vaccinated mice lysed human umbilical vascular endothelial cells, but not tumor cells in vitro, in a dose‐dependent manner. Furthermore, adoptive transfer of antitumor EP antibodies in vivo targeted to tumor endothelium and inhibited spontaneous LLC tumor metastasis. This study provides a successful preclinical exploration of the active immunotherapy for tumor by targeting tumor angiogenesis. © 2009 UICC
Increased production and secretion of HGF α‐chain and an antagonistic HGF fragment in a human breast cancer progression model
Authors: Wright Theodore G. , Singh Vinay K. , Li John J. , Foley Jonathan H. , Miller Fred , Jia Zongchao , Elliott Bruce E. 
Published: February 2009

AbstractInvasive human breast carcinomas frequently coexpress increased hepatocyte growth factor (HGF) and its receptor Met, suggesting that establishment of an autocrine HGF loop is important in malignant disease. This study examines the expression patterns of HGF and Met activation during tumorigenesis and metastasis using a MCF10A‐based model of Ha‐Ras‐induced human breast cancer progression. Deregulation of cadherin‐based cell‐cell adhesions, decreased expression of cytokeratins 8/18 and increased activity of matrix metalloproteinases such as MMP‐2 occurs in premalignant and malignant (metastatic) cell lines compared to the parental nonmalignant cell line. Compared to the benign parent cell line, premalignant and malignant cell lines exhibit increased secretion of full length HGF α‐chain and elevated Met tyrosine phosphorylation in complete medium. Interestingly, the premalignant and malignant cells also secrete a ∼55 kDa HGF fragment. Epitope mapping of the ∼55 kDa HGF fragment supports the presence of the N‐terminal domain of the HGF α‐chain with a truncation in the C‐terminal domain. The ∼55 kDa HGF fragment shows mobility in SDS‐PAGE faster than HGF α‐chain, but slightly slower than NK4, a previously established full antagonist of HGF. The separated ∼55 kDa HGF fragment binds to animmobilized Met‐IgG fusion protein, and inhibits both HGF/Met‐IgG binding and HGF‐induced Met‐tyrosine phosphorylation. These results are the first demonstration of an antagonistic ∼55 kDa HGF fragment secreted during breast carcinoma progression, which may have a negative regulatory effect on HGF signaling in premalignant breast epithelial cells. © 2009 UICC
Proteomic analysis reveals upregulation of RKIP in S‐180 implanted BALB/C mouse after treatment with ascorbic acid
Authors: Park Seyeon , Ahn Eun Sook , Lee Sukchan , Jung Manyong , Park Jin Hee , Yi Sang Yeop , Yeom Chang‐Hwan 
Published: February 2009

AbstractTumor cells have an invasive and metastatic phenotype that is the main cause of death for cancer patients. Tumor establishment and penetration consists of a series of complex processes involving multiple changes in gene expression. In this study, intraperitoneal administration of a high concentration of ascorbic acid inhibited tumor establishment and increased survival of BALB/C mice implanted with S‐180 sarcoma cancer cells. To identify proteins involved in the ascorbic acid‐mediated inhibition of tumor progression, changes in the liver proteome associated with ascorbic acid treatment of BALB/C mice implanted with S‐180 were investigated using two‐dimensional gel electrophoresis and mass spectrometry. Eleven protein spots were identified whose expression was different between control and ascorbic acid treatment groups. In particular, Raf kinase inhibitory protein (RKIP) and annexin A5 expression were quantitatively up‐regulated. The increase in RKIP protein level was detected in the tumor tissue and accompanied by an increase in mRNA level. Our results suggest a possibility that these proteins are related to the ascorbic acid‐mediated suppression of tumor formation. J. Cell. Biochem. 106: 1136–1145, 2009. © 2009 Wiley‐Liss, Inc.
ERK2 and CREB activation in the amygdala when an event is remembered as “Fearful” and not when it is remembered as “Instructive”
Authors: Ilin Yana , Richter‐Levin Gal 
Published: February 2009

AbstractA training protocol was developed based on durable exposure to the two‐way shuttle avoidance task, in which the conditioned stimulus (CS), which was fear evoking for both training conditions on the first day of training, becomes instructive at the end of training under controllable conditions but remains fear evoking under the uncontrollable conditions. The protocol was utilized to examine whether, depending on the training regime, the memory formed will result in a different level of involvement of the amygdala. Three groups of rats were tested: controllable, subjected to durable avoidance learning; uncontrollable, subjected to the same training schedule but with no control over the stressor; and naïve. Two weeks later, after the introduction of a reminder cue, freezing response, defecation, and blood corticosterone (CORT) of the uncontrollable group were higher than in the controllable and naïve groups, indicating that indeed, for this group, the CS remained fear evoking. Significantly higher than chance shuttling responses of the controllable group indicated that, for them, the CS became ”instructive.” Activation of ERK2 and CREB in the basolateral amygdala (BLA) was highest in the uncontrollable group compared with the controllable and naïve groups. Overall, the results indicate that the training procedure succeeded in dissociating between the physical (electric shock) and the psychological (control) attributes of the experience. Also, our findings support the view that an emotionally charged reminder cue activates the amygdala but that, as a previously fear‐evoking memory cue becomes instructive, the involvement of the amygdale lessens. © 2009 Wiley‐Liss, Inc.
Utility of lymphoblastoid cell lines
Authors: Sie L. , Loong S. , Tan E. K. 
Published: February 2009

AbstractTransformation of peripheral B lymphocytes by Epstein‐Barr virus (EBV) is the method of choice for generating lymphoblastoid cell lines (LCLs). This method has been in use for the last two decades with a high success rate. With a somatic mutation rate of 0.3% and ease of cell maintenance, lymphoblastoid cells are still the preferred choice of storage for patients' genetic material. Studies have demonstrated a good correlation between using DNA from patient‐derived LCLs and conventional sources for the purpose of genetic screening. RNAs from LCLs have also been utilized for detecting splice mutations in various diseases. There is increasing evidence that gene expression in LCLs encompasses a wide range of metabolic pathways that are specific to individuals where the cells originated, making LCLs suitable for molecular and functional studies. There have been efforts to produce a proteome map and database of lymphoblastoid cells by characterizing protein spots on a two‐dimensional electrophoresis map. Proteomes from LCLs have been used in the elucidation of protein expression profile analysis of cellular response to DNA double‐strand break, an approach now recognized as differential proteome analysis. Despite some inherent limitations, the utility of LCLs is increasingly recognized and with appropriate infrastructure and financial support, LCLs will be an important resource for genetic and functional research of neurological disorders. © 2009 Wiley‐Liss, Inc.
Adult CST‐null mice maintain an increased number of oligodendrocytes
Authors: Shroff S.M. , Pomicter A.D. , Chow W.N. , Fox M.A. , Colello R.J. , Henderson S.C. , Dupree J.L. 
Published: February 2009

AbstractThe galactolipids galactocerebroside and sulfatide have been implicated in oligodendrocyte (OL) development and myelin formation. Much of the early evidence for myelin galactolipid function has been derived from antibody and chemical perturbation of OLs in vitro. To determine the role of these lipids in vivo, we previously characterized mice lacking galactocerebroside and sulfatide and observed abundant, unstable myelin and an increased number of OLs. We have also reported that mice incapable of synthesizing sulfatide (CST‐null) while maintaining normal levels of galactocerebroside generate relatively stable myelin with unstable paranodes. Additionally, Hirahara et al. (2004; Glia 45:269–277) reported that these CST‐null mice also contain an increased number of OLs in the forebrain, medulla, and cerebellum at 7 days of age. Here, we further the findings of Hirahara et al. by demonstrating that the number of OLs in the CST‐null mice is also increased in the spinal cord and that this elevated OL population is maintained through, at least, 7 months of age. Moreover, we show that the enhanced OL population is accompanied by increased proliferation and decreased apoptosis of oligodendrocytic‐lineage cells. Finally, through ultrastructural analysis, we show that the CST‐null OLs exhibit decreased morphological complexity, a feature that may result in decreased OL competition and increased OL survival. © 2009 Wiley‐Liss, Inc.
Intrastriatal lipopolysaccharide injection induces parkinsonism in C57/B6 mice
Authors: Hunter Randy L. , Cheng Baohua , Choi Dong‐Young , Liu Mei , Liu Shuwei , Cass Wayne A. , Bing Guoying 
Published: February 2009

AbstractA role for inflammation has been hypothesized in the etiology and progression of Parkinson's disease (PD). In this study, we generated, characterized, and validated the first progressive PD‐related mouse model (C57/B6) with intrastriatal injection of lipopolysaccharide (LPS). We showed progressive and specific dopaminergic neurodegeneration in the substantia nigra, which is accompanied by striatal dopamine depletion and progressive behavioral impairment, which was alleviated by the use of the PD drug L‐Dopa. We focused on the role of nitric oxide (NO) in inflammation‐promoted cell death and suggest that the expression of the inducible NO synthase plays a role in the progressive loss of dopaminergic neurons but not the initial loss induced by LPS. With this model, future research can be performed in gene knockout mice to study other potential mechanisms of inflammation‐induced neurodegeneration. In addition, this model can be used to screen therapeutics for PD at a more clinically relevant time (i.e., after LPS injection but before manifestation of PD‐related behavioral impairment), because most PD drugs are screened in animal models in which inhibitors are given predisease induction. Thus, this novel PD‐related model should be further characterized and strongly considered as a tool for future drug studies. © 2009 Wiley‐Liss, Inc.
Multiple functions of the paranodal junction of myelinated nerve fibers
Authors: Rosenbluth Jack 
Published: February 2009

AbstractMyelin sheaths include an extraordinary structure, the “paranodal axoglial junction” (PNJ), which attaches the sheath to the axon at each end of each myelin segment. Its size is enormous and its structure unique. Here we review past and current studies showing that this junction can serve multiple functions in maintaining reliable saltatory conduction. The present evidence points to three functions in particular. 1) It seals the myelin sheath to the axon to prevent major shunting of nodal action currents beneath the myelin sheath while still leaving a narrow channel interconnecting the internodal periaxonal space with the perinodal space. This pathway represents a potential route through which juxtaparanodal and internodal channels can influence nodal activity and through which nutrients, such as glucose, and other metabolites can diffuse to and from the internodal periaxonal space. 2) It serves as a mechanism for maintaining discrete, differentiated axolemmal domains at and around the node of Ranvier by acting as a barrier to the lateral movement of ion channel complexes within the axolemma, thus concentrating voltage‐gated sodium channels at the node and segregating fast voltage‐gated potassium channels to the juxtaparanode under the myelin sheath. 3) It attaches the myelin sheath to the axon on either side of the node and can thus maintain nodal dimensions in the face of mechanical stresses associated with stretch or other local factors that might cause disjunction. It is therefore the likely means for maintaining constancy of nodal surface area and electrical parameters essential for consistency in conduction. © 2009 Wiley‐Liss, Inc.