bluuebunny/crossref_metadata_2025_split huggingface dataset:
L‐type amino acid transporter 1 as a potential molecular target in human astrocytic tumors
Authors: Nawashiro Hiroshi , Otani Naoki , Shinomiya Nariyoshi , Fukui Shinji , Ooigawa Hidetoshi , Shima Katsuji , Matsuo Hirotaka , Kanai Yoshikatsu , Endou Hitoshi 
Published: February 2006

AbstractL‐type amino acid transporter 1 (LAT1) is a Na+‐independent neutral amino acid transport agency and essential for the transport of large neutral amino acids. LAT1 has been identified as a light chain of the CD98 heterodimer from C6 glioma cells. LAT1 also corresponds to TA1, an oncofetal antigen that is expressed primarily in fetal tissues and cancer cells. We have investigated for the first time, the expression of the transporter in the human primary astrocytic tumor tissue from 60 patients. LAT1 is unique because it requires an additional single membrane spanning protein, the heavy chain of 4F2 cell surface antigen (4F2hc), for its functional expression. 4F2hc expression was also determined by immunohistochemistry. Kaplan‐Meier analyses demonstrated that high LAT1 expression correlated with poor survival for the study group as a whole (p < 0.0001) and for those with glioblastoma multiforme in particular (p = 0.0001). Cox regression analyses demonstrated that LAT1 expression was one of significant predictors of outcome, independent of all other variables. On the basis of these findings, we also investigated the effect of the specific inhibitor to LAT1, 2‐aminobicyclo‐2 (2,2,1)‐heptane‐2‐carboxylic acid (BCH), on the survival of C6 glioma cells in vitro and in vivo using a rat C6 glioma model. BCH inhibited the growth of C6 glioma cells in vitro and in vivo in a dose‐dependent manner. Kaplan‐Meier survival data of rats treated with BCH were significant. These findings suggest that LAT1 could be one of the molecular targets in glioma therapy. © 2006 Wiley‐Liss, Inc.
Association of a functional polymorphism in the promoter of the MDM2 gene with risk of nonsmall cell lung cancer
Authors: Lind Helge , Zienolddiny Shanbeh , Ekstrøm Per Olav , Skaug Vidar , Haugen Aage 
Published: February 2006

AbstractLung cancer is the leading cause of cancer mortality in the world. Although exposure to carcinogens is considered to be the main cause, genetic variation may contribute to lung cancer risk. Murine double minute 2, MDM2, is a key regulator of p53 activity and recently a polymorphism in the promoter region of the MDM2 gene was characterized. This single nucleotide polymorphism, SNP309, was shown to influence MDM2 transcription, MDM2 protein levels and p53 activity. The aim of this study was to investigate whether this functionally important SNP is associated with risk of nonsmall cell lung cancer. The study consisted of 341 nonsmall cell lung cancer cases and 412 healthy controls of Norwegian origin. Our results indicate that the G/G genotype of SNP309 is associated with lung cancer risk with an odds ratio of 1.62 (95% CI: 1.06–2.50). Interestingly, the strongest effect of the polymorphism was seen among women. Females homozygous for SNP309 G/G had associated odds ratio 4.06 (1.29–12.8). We also explored the MDM2 SNP309 in relation to TP53 gene mutations and age at nonsmall cell lung cancer diagnosis. Our results indicate that the G/G genotype of SNP309 is associated with higher age at diagnosis in individuals with TP53 mutations (p = 0.037). © 2006 Wiley‐Liss, Inc.
Cigarette smoking and colorectal cancer risk in Germany: A population‐based case–control study
Authors: Verla‐Tebit Emaculate , Lilla Carmen , Hoffmeister Michael , Brenner Hermann , Chang‐Claude Jenny 
Published: February 2006

AbstractStudies have shown fairly consistent positive relationships between smoking and risk of colorectal adenomas, but have yielded inconsistent results for colorectal cancer. Issues relating to the duration, cumulative dose of smoking and the effect of smoking cessation on colorectal cancer risk still need clarification. In a population‐based case–control study in Germany, we recruited 540 incident cases of colorectal cancer and 614 controls matched to cases by sex, 5‐year age groups and county of residence from January 2003 to June 2004. Subjects were aged ≥30 years, and provided information on risk factors of colorectal cancer, including lifetime cigarette smoking habits, in personal interviews. Odds ratios (OR) and 95% confidence intervals (CI) were computed using conditional logistic regression models, adjusting for potential confounders. Compared with nonsmokers, there was an increased risk for smoking for ≥30 years (OR: 1.25, 95% CI: 0.90–1.75) and a significant risk increase for ≥40 pack‐years of smoking (OR: 1.92, 95% CI: 1.13–3.28). Stratification by sex yielded higher risk estimates among females than that among males, with adjusted ORs of 3.5 (95% CI: 1.29–9.52) and 1.15 (0.69–1.91) for women and men, respectively, following ≥30 pack‐years of smoking (pinteraction = 0.18). Among smokers, risk reduction was observed after ≥20 years of quitting smoking and was significant for ≥40 years (OR: 0.46; 95% CI: 0.21–0.98), when compared to current smokers (p for linear trend = 0.05). This study supports the hypothesis that smoking for a long duration at a high cumulative dose increases the risk for colorectal cancer, particularly among women, and suggests that there is risk reduction after longterm smoking cessation. © 2006 Wiley‐Liss, Inc.
Basic fibroblast growth factor endows dorsal telencephalic neural progenitors with the ability to differentiate into oligodendrocytes but not γ‐aminobutyric acidergic neurons
Authors: Abematsu Masahiko , Kagawa Tetsushi , Fukuda Shinji , Inoue Toshihiro , Takebayashi Hirohide , Komiya Setsuro , Taga Tetsuya 
Published: February 2006

AbstractBasic fibroblast growth factor (bFGF) is commonly used to enrich and maintain neural stem cells in vitro. Olig2 is an essential transcription factor for oligodendrocyte lineage specification and is expressed predominantly in ventral neuroepithelial cells in the medial and lateral ganglionic eminence (GE), where oligodendrocyte progenitors originate. Here we report significant induction of Olig2 expression in dorsal neuroepithelium‐derived cells cultured in the presence of bFGF, in which Olig2‐expressing cells were initially negligible. Among Olig2‐expressing cells appearing after a 5‐day treatment with bFGF, 99.8% coexpressed nestin. There was no significant difference in proliferation or apoptosis in dorsal and ventral neuroepithelial cultures in the presence of bFGF, suggesting that bFGF induces ectopic expression of Olig2 in dorsal “cortical” neuroepithelial cells. Similarly, expression of Mash1, another ventral neuroepithelial cell marker gene, was also induced in cultured dorsal neuroepithelial cells in the presence of bFGF. Conversely, in this culture, expression of dorsal neuroepithelial cell markers, such as Neurogenin1, Neurogenin2, Pax6, and Emx2, was down‐regulated. These results suggested a possible ventralizing activity of bFGF. In fact, bFGF‐treated dorsal neuroepithelial cells acquired the potential to generate O4‐positive oligodendrocytes with efficacy comparable to that observed with GE‐derived cells. In marked contrast, bFGF did not enable dorsal neuroepithelial cells to generate γ‐aminobutyric acid (GABA) neurons, which normally develop only from GE in vivo. Thus, bFGF endows dorsal telencephalic neural progenitors with the ability to differentiate into oligodendrocytes but not GABAergic neurons, suggesting the presence of different mechanisms governing specification of dorsoventral cell identities of neuronal and glial cell lineages. © 2006 Wiley‐Liss, Inc.
Increased glia‐specific transgene expression with glial fibrillary acidic protein promoters containing multiple enhancer elements
Authors: de Leeuw Bertie , Su Mu , Horst Maarten ter , Iwata Shingo , Rodijk Mark , Hoeben Rob C. , Messing Albee , Smitt Peter Sillevis , Brenner Michael 
Published: February 2006

AbstractThe ability to direct transgene expression to astrocytes has become increasingly important as the roles for these cells continue to expand. Promoters consisting of the 5′‐flanking region of the human or mouse glial fibrillary acidic protein (GFAP) gene have generally proved satisfactory. However, a more powerful promoter would be advantageous for several applications, such as expression of dominant negative RNAs or proteins, or for gene therapy. We investigated the possibility of increasing the transcriptional activity of the human GFAP promoter by inserting into it one or three additional copies of putative GFAP enhancer regions. The promoters enhanced with three additional copies gave 75‐fold higher LacZ expression levels upon plasmid transfection into GFAP‐expressing U251 cells than the parental gfa2 promoter. Surprisingly, in a transgenic mouse model, the enhanced promoters resulted in no or only very low expression of marker genes, probably caused by toxicity. When various cell lines were infected with replication‐deficient adenoviral vectors, the enhanced promoters gave LacZ expression levels that were approximately 10‐fold higher than those with the parental gfa2 promoter, while retaining specificity for GFAP‐expressing cells. Injection of the adenoviral vectors carrying the enhanced promoters into nude mouse brain showed that LacZ expression was limited to GFAP‐positive cells. We conclude that gfa2 enhanced promoters are useful for production of short‐term, glia‐specific, high expression levels of genes in an adenoviral context. Adenoviral vectors containing these enhanced promoters may be useful in glioma gene therapy. © 2006 Wiley‐Liss, Inc.
Huperzine a attenuates mitochondrial dysfunction in β‐amyloid‐treated PC12 cells by reducing oxygen free radicals accumulation and improving mitochondrial energy metabolism
Authors: Gao Xin , Tang Xi Can 
Published: February 2006

AbstractWe observed previously that huperzine A (HupA), a selective acetylcholinesterase inhibitor, can counteract neuronal apoptosis and cell damage induced by several neurotoxic substances, and that this neuroprotective action somehow involves the mitochondria. We investigated the ability of HupA to reduce mitochondrial dysfunction in neuron‐like rat pheochromocytoma (PC12) cells exposed in culture to the amyloid β‐peptide fragment 25–35 (Aβ25–35). After exposure to 1 μM Aβ25–35for various periods, cells exhibited a rapid decline of ATP levels and obvious disruption of mitochondrial membrane homeostasis and integrity as determined by characteristic morphologic alterations, reduced membrane potential, and decreased activity of ion transport proteins. In addition, Aβ25–35treatment also led to inhibition of key enzyme activities in the electron transport chain and the tricarboxylic acid cycle, as well as an increase of intracellular reactive oxygen species (ROS). Pre‐incubation with HupA for 2 hr not only attenuated these signs of cellular stress caused by Aβ, but also enhanced ATP concentration and decreased ROS accumulation in unharmed normal cells. Those results indicate that HupA protects mitochondria against Aβ‐induced damages, at least in part by inhibiting oxidative stress and improving energy metabolism, and that these protective effects reduce the apoptosis of neuronal cells exposed to this toxic peptide. © 2006 Wiley‐Liss, Inc.
Long‐term effects of stroke on neuronal rest activity in rolandic cortical areas
Authors: Tecchio F. , Zappasodi F. , Pasqualetti P. , Tombini M. , Caulo M. , Ercolani M. , Rossini P.M. 
Published: February 2006

AbstractTo understand the relationship between neuronal function and clinical state in the framework of stroke, the long‐term poststroke rolandic spontaneous neuronal activity was studied by means of magnetoencephalography. Fifty‐six patients who had suffered a unilateral stroke within the middle cerebral artery were enrolled. Median time since stroke was 2.8 years. In association with lesion features and clinical picture, total and relative band powers and the spectral entropy were analyzed in the affected (AH) and unaffected (UH) hemispheres in comparison with an age‐matched control group. An increase of absolute and relative slow band powers and a reduction of relative fast band powers were found in patients' AH with respect to both UH and control values. Absolute delta band was higher than in controls also in UH. New findings were the increase of rolandic rest activity power also in the alpha band and the decrease of spectral entropy in AH with respect to both UH and control values. Moreover, our results in chronic stroke patients indicate frequency‐selective alterations related to specific dysfunctions: global clinical status was mostly impaired in patients with larger lesions and increased total and slow band activity powers, whereas hand functionality was mostly disrupted in patients with subcortical involvement and reduction of high‐frequency rhythms and spectral entropy. Total power increase and spectral richness decrease are in agreement with a higher synchrony of local neuronal activity, a reduction of the intracortical inhibitory network's efficiency, and an increase of neuronal excitability. © 2006 Wiley‐Liss, Inc.
Transplantation of hNT neurons into the ischemic cortex: Cell survival and effect on sensorimotor behavior
Authors: Bliss T.M. , Kelly S. , Shah A.K. , Foo W.C. , Kohli P. , Stokes C. , Sun G.H. , Ma M. , Masel J. , Kleppner S.R. , Schallert T. , Palmer T. , Steinberg G.K. 
Published: February 2006

AbstractCell transplantation offers a potential new treatment for stroke. Animal studies using models that produce ischemic damage in both the striatum and the frontal cortex have shown beneficial effects when hNT cells (postmitotic immature neurons) were transplanted into the ischemic striatum. In this study, we investigated the effect of hNT cells in a model of stroke in which the striatum remains intact and damage is restricted to the cortex. hNT cells were transplanted into the ischemic cortex 1 week after stroke induced by distal middle cerebral artery occlusion (dMCAo). The cells exhibited robust survival at 4 weeks posttransplant even at the lesion border. hNT cells did not migrate, but they did extend long neurites into the surrounding parenchyma mainly through the white matter. Neurite extension was predominantly toward the lesion in ischemic animals but was bidirectional in uninjured animals. Extension of neurites through the cortex toward the lesion was also seen when there was some surviving cortical tissue between the graft and the infarct. Prolonged deficits were obtained in four tests of sensory‐motor function. hNT‐transplanted animals showed a significant improvement in functional recovery on one motor test, but there was no effect on the other three tests relative to control animals. Thus, despite clear evidence of graft survival and neurite extension, the functional benefit of hNT cells after ischemia is not guaranteed. Functional benefit could depend on other variables, such as infarct location, whether the cells mature, the behavioral tests employed, rehabilitation training, or as yet unidentified factors. © 2006 Wiley‐Liss, Inc.
Extracellular signal‐regulated kinases 1/2 are required for adult retinal ganglion cell axon regeneration induced by fibroblast growth factor‐2
Authors: Sapieha Przemyslaw S. , Hauswirth William W. , Di Polo Adriana 
Published: February 2006

AbstractThe intracellular signaling mechanisms used by neurotrophic factors to promote axon growth in the mature, injured central nervous system are not well understood. Here we investigated the signaling cascades that control fibroblast growth factor‐2 (FGF‐2)‐mediated retinal ganglion cell (RGC) axon extension in vivo. For this purpose, a novel adeno‐associated virus (AAV) was used to deliver the FGF‐2 gene to RGCs, providing a sustained source of this neurotrophic factor. FGF‐2 gene transfer led to an approximately ten‐fold increase in the number of axons that extended past the lesion site compared with control nerves. Axon growth correlated with FGF‐2‐induced activation of the extracellular signal‐regulated kinases 1/2 (Erk1/2), but not phosphoinositide 3‐kinase or protein kinase C. Pharmacological inhibition of Erk1/2 activation resulted in an ∼80% decrease in the number of axons that regenerated in the injured optic nerve. Our data demonstrate that the Erk1/2 pathway is an essential signaling component in FGF‐2‐mediated axon regeneration in the mature, injured visual system. © 2006 Wiley‐Liss, Inc.
The Rho‐family guanine nucleotide exchange factor GEFT enhances retinoic acid‐ and cAMP‐induced neurite outgrowth
Authors: Bryan Brad A. , Cai Yi , Liu Mingyao 
Published: February 2006

AbstractThe Rho GTPases are important regulators of neurite outgrowth and pathfinding. We have recently reported that a Rho‐family guanine nucleotide exchange factor, GEFT, modulates dendrite spine morphology and basal neurite outgrowth in primary hippocampal neurons and Neuro2A cells, respectively. Here we demonstrate that GEFT protein is highly expressed in all regions of the brain and is highly up‐regulated upon treatment of Neuro2A cells with retinoic acid and dibutyric cAMP, which promote dendrite and axon‐like neurite extensions, respectively. Within retinoic acid‐induced neurite extensions, GEFT is localized to actin‐enriched regions in the primary neurites, with little or no expression from secondary branches. Dibutyric cAMP‐induced neurite extensions are highly concentrated for GEFT at the actin‐rich distal tip of the growth cone. Additionally, we demonstrate that GEFT promotes neurite outgrowth in undifferentiated as well as differentiated Neuro2A cells. Together, our data provide new evidence suggesting that GEFT is an important regulator of multiple processes involved in axon and dendrite formation. © 2006 Wiley‐Liss, Inc.
Raman, FT‐IR and DFT studies of ortho‐, meta‐ and para‐pyridinomethylene substituted di(4‐hydroxy‐coumarin) and their Ce(III), La(III) and Nd(III) complexes
Authors: Georgieva I. , Kostova I. , Trendafilova N. , Rastogi V. K. , Bauer G. , Kiefer W. 
Published: February 2006

AbstractVibrational spectra of ortho‐, meta‐ and para‐pyridinomethylene substituted di(4‐hydroxycoumarin) (o‐, m‐, p‐PyDC, (PyDCs)) and their Ce(III), La(III) and Nd(III) complexes were studied by Raman and Fourier transform infrared (FT‐IR) spectroscopies. Density functional theory (DFT) at B3LYP/6‐31G(d) level was used to determine the geometrical and vibrational characteristics of the neutral PyDC isomers and their dianionic forms. The experimental IR and Raman bands of PyDCs were assigned to the corresponding normal modes on the basis of DFT calculations. The effect of the intramolecular H‐bonds in PyDCs as well as of the PyDCs deprotonation on the vibrational mode positions was estimated by comparison with the molecular vibrations of the H‐bonding‐free 4‐hydroxycoumarin and PyDC dianionic forms. The characteristic IR and Raman bands of o‐, m‐ and p‐PyDC were specified and discussed. The comparative vibrational analysis of the neutral and the dianionic PyDCs and their Ln(III) complexes gave evidence that the PyDC ligands bound the lanthanide(III) through the carbonylic oxygens and the deprotonated hydroxylic oxygens. Copyright © 2006 John Wiley & Sons, Ltd.
Lymphoscintigraphic drainage of acral limb skin to interval sentinel lymph nodes in healthy subjects
Authors: Aydin Mustafa Asim , Okudan Berna , Nasir Serdar , Özbek Meltem , Karagöz Arif , Altuntaş Selman 
Published: February 2006

AbstractBackground and ObjectivesIn the literature, drainage to epitrochlear and popliteal sentinel lymph nodes (SLN) are analyzed for whole or distal extremity (below elbow or knee) melanomas that are not topographically homogeneous with respect to tendency of drainage to interval SLNs. We hypothesize that acral (hand and foot) skin has a uniform frequency of drainage to interval SLNs, which is higher than reported for distal extremity melanomas.MethodsOne hundred healthy subjects were enrolled. Fifty subjects had standard four extremity lymphoscintigraphies by radiocolloid injection into an interdigital web space as in lymphodynamic studies. On another 50 subjects, either targeted upper (n = 25) or lower (n = 25) extremity lymphoscintigraphies were performed utilizing injection sites that likely drain to interval SLNs. Acral skin drainage to interval SLNs was analyzed for interindividual variability and injection site dependence.ResultsThere was considerable interindividual variability in drainage of each injection site to interval SLNs. Hand skin had a uniform 50% frequency of drainage to epitrochlear–midhumeral SLNs with both injection sites. This frequency was higher than the epitroclear SLN frequencies reported for distal extremity melanomas. Foot skin had 10% and 90% frequencies of drainage to popliteal SLNs from standard and targeted injection sites, respectively. Foot skin largely simulates the tendency of drainage reported for distal extremity melanomas while lateral heel represents a limited zone that almost uniformly drains to popliteal SLNs.ConclusionsDespite dissimilarities between hand and foot, acral skin drainage to interval SLNs is high enough to obligate a thorough interval SLN exploration in acral primaries. J. Surg. Oncol. 2006;93:286–293. © 2006 Wiley‐Liss, Inc.
Transpleurodiaphragmatic cryosurgical ablation for recurrent unresectable colorectal liver metastases
Authors: Stella Mattia , Mithieux François , Meeus Pierre , Kaemmerlen Pierre , Lafon Cyril , Rivoire Michel 
Published: February 2006

AbstractBackground and ObjectivesCryosurgical ablation (CSA) allows the focal destruction of unresectable liver metastases after previous liver resection. The abdominal approach may be difficult for recurrent colorectal cancer metastases located in the upper part of the remaining liver, close to the inferior vena cava (IVC), the hepatic veins, and the diaphragm. A transpleurodiaphragmatic access was assessed for safety and efficacy.MethodsBetween September 1999 and July 2004, 13 patients with recurrent unresectable colorectal liver metastases underwent transpleurodiaphragmatic CSA via limited right thoracotomy. Seventeen lesions were treated; median diameter was 31 mm (range 13–40 mm). One to three cryoprobes were used, depending on the size and location of metastases.ResultsThere was no operative death; three patients developed minor complications (23%). Median hospital stay was 10 days (8–14 days). After a median follow‐up of 26 months (range 8–69 months), 9 patients were alive, and 5 were disease‐free. Six patients had liver recurrences outside the cryolesion. Median disease free survival was 12 months with 60% 3‐year survival after CSA and 58% 5‐year survival after first liver surgery.ConclusionsTranspleurodiaphragmatic CSA is safe and effective in selected patients with unresectable recurrent liver metastases from colorectal cancer. J. Surg. Oncol. 2006;93: 268–272. © 2006 Wiley‐Liss, Inc.