bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti‐tumor activity of the combination of cetuximab, an anti‐EGFR blocking monoclonal antibody and ZD6474, an inhibitor of VEGFR and EGFR tyrosine kinases
Authors: Morelli Maria Pia , Cascone Tina , Troiani Teresa , Tuccillo Concetta , Bianco Roberto , Normanno Nicola , Romano Marco , Veneziani Bianca Maria , Fontanini Gabriella , Eckhardt S. Gail , De Pacido Sabino , Tortora Giampaolo , Ciardiello Fortunato 
Published: May 2006

AbstractPurpose: The epidermal growth factor receptor (EGFR) autocrine pathway plays an important role in cancer cell growth. Vascular endothelial growth factor A (VEGF‐A) is a key regulator of tumor‐induced endothelial cell proliferation and vascular permeability. ZD6474 is an orally available, small molecule inhibitor of VEGF receptor‐2 (VEGFR‐2), EGFR and RET tyrosine kinase activity. We investigated the activity of ZD6474 in combination with cetuximab, an anti‐EGFR blocking monoclonal antibody, to determine the anti‐tumor activity of EGFR blockade through the combined use of two agents targeting the receptor at different molecular sites in cancer cells and of VEGFR‐2 blockade in endothelial cells. Experimental Design: The anti‐tumor activity in vitro and in vivo of ZD6474 and/or cetuximab was tested in human cancer cell lines with a functional EGFR autocrine pathway. Results: The combination of ZD6474 and cetuximab determined synergistic growth inhibition in all cancer cell lines tested as assessed by the Chou and Talalay method. In nude mice bearing established human colon carcinoma (GEO) or lung adenocarcinoma (A549) xenografts and treated with ZD6474 and/or cetuximab for 4 weeks, a reversible tumor growth inhibition was caused by each drug. In contrast, a more significant tumor growth delay resulted from the combination of the two agents with an approximately 100–110 days increase in mice median overall survival as compared to single agent treatment. Conclusions: This study provides a rationale for evaluating in a clinical setting the double blockade of EGFR in combination with inhibition of VEGFR‐2 signaling as cancer therapy. J. Cell. Physiol. 208: 344–353, 2006. © 2006 Wiley‐Liss, Inc.
Utility of intraperitoneal administration as a route of AAV serotype 5 vector‐mediated neonatal gene transfer
Authors: Ogura Tsuyoshi , Mizukami Hiroaki , Mimuro Jun , Madoiwa Seiji , Okada Takashi , Matsushita Takashi , Urabe Masashi , Kume Akihiro , Hamada Hiromi , Yoshikawa Hiroyuki , Sakata Yoichi , Ozawa Keiya 
Published: May 2006

AbstractBackgroundGene transfer into a fetus or neonate can be a fundamental approach for treating genetic diseases, particularly disorders that have irreversible manifestations in adulthood. Although the potential utility of this technique has been suggested, the advantages of neonatal gene transfer have not been widely investigated. Here, we tested the usefulness of neonatal gene transfer using adeno‐associated virus (AAV) vectors by comparing the administration routes and vector doses.MethodsTo determine the optimal administration route, neonates were subjected to intravenous (iv) or intraperitoneal (ip) injections of AAV5‐based vectors encoding the human coagulation factor IX (hfIX) gene, and the dose response was examined. To determine the distribution of transgene expression, vectors encoding lacZ or luciferase (luc) genes were used and assessed by X‐gal staining and in vivo imaging, respectively. After the observation period, the vector distribution across tissues was quantified.ResultsThe factor IX concentration was higher in ip‐injected mice than in iv‐injected mice. All transgenes administered by ip injection were more efficiently expressed in neonates than in adults. The expression was confined to the peritoneal tissue. Interestingly, a sex‐related difference was observed in transgene expression in adults, whereas this difference was not apparent in neonates.ConclusionsAAV vector administration to neonates using the ip route was clearly advantageous in obtaining robust transgene expression. Vector genomes and transgene expression were observed mainly in the peritoneal tissue. These findings indicate the advantages of neonatal gene therapy and would help in designing strategies for gene therapy using AAV vectors. Copyright © 2006 John Wiley & Sons, Ltd.
Ischemic tolerance in chemical preconditioning: Possible role of astrocytic glutamine synthetase buffering glutamate‐mediated neurotoxicity
Authors: Hoshi Akihiko , Nakahara Toshiki , Kayama Hisae , Yamamoto Teiji 
Published: May 2006

AbstractGlutamine synthetase (GS), localized to astrocyte is a key enzyme in the glutamate‐glutamine pathway in the brain. 3‐Nitropropionic acid (3‐NPA) is an irreversible inhibitor of succinate dehydrogenase in the tricarboxylic‐acid cycle, and provides ischemic tolerance to the brain. So far, there have been no reports on the relationship of astrocytic GS and ischemic tolerance by chemical preconditioning. In order to test the hypothesis that astrocytes serve a pivotal role in 3‐NPA‐induced chemical preconditioning, we have investigated the temporal profile of GS expression in astrocyte parallel with those of glial fibrillary acidic protein and heat‐shock protein 70 (HSP70). In our rat model of permanent focal ischemia, preconditioning with 3‐NPA singnificantly reduced the subsequent neurological deficits and infarct volume within 24–72 hours after treatment. Immunohistochemically, protoplasmic astrocytes in the cortex and striatum were activated in terms of upregulation of GS and more abundant protoplasmic processes with 3‐NPA preconditioning, however, HSP70 expression could not be induced. Thus, the activation of astrocytes and upregulation of GS play an important role in 3‐NPA‐induced preconditioning but HSP70 does not. In view of glutamate being imposed on the cerebral ischemic damage, the astrocytic GS may contribute to 3‐NPA‐induced ischemic tolerance. © 2006 Wiley‐Liss, Inc.
Iron (Fe) bioavailability and the distribution of anti‐Fe nutrition biochemicals in the unpolished, polished grain and bran fraction of five rice genotypes
Authors: Prom‐u‐thai Chanakan , Huang Longbin , Glahn Raymond P , Welch Ross M , Fukai Shu , Rerkasem Benjavan 
Published: May 2006

AbstractIron (Fe) bioavailability in unpolished, polished grain and bran fraction of five rice genotypes with a range of Fe contents was measured by in vitro digestion and cultured Caco‐2 cells of cooked grain. There was a significant difference in Fe bioavailability among the five rice genotypes tested, in both the unpolished and polished grain. The range of Fe bioavailability variation in polished rice was much wider than that of unpolished, suggesting the importance of using Fe levels and bioavailability in polished rice grain as the basis for selecting high‐Fe rice cultivars for both agronomic and breeding purposes. Milling and polishing the grain to produce polished (or white) rice increased Fe bioavailability in all genotypes. Iron bioavailability in polished rice was high in the UBON2 and Nishiki, intermediate in both IR68144 and KDML105, and low in CMU122. All genotypes had low bioavailability of Fe in bran fraction compared to unpolished and polished grain, except in CMU122. CMU122 contained the lowest level of bioavailable Fe in unpolished and polished grain and bran, because of the dark purple pericarp colored grain and associated tannin content. The level of bioavailable Fe was not significantly correlated with grain Fe concentration or grain phytate levels among these five genotypes tested. The negative relationship between Fe bioavailability and the levels of total extractable phenol was only observed in unpolished (r = −0.83**) and bran fraction (r = −0.50*). The present results suggested that total extractable phenol and tannin contents could also contribute to lowering bioavailability of Fe in rice grain, in addition to phytate. Copyright © 2006 Society of Chemical Industry
Molecular and cellular targets
Authors: Bode Ann M. , Dong Zigang 
Published: May 2006

AbstractCarcinogenesis is a multistage process consisting of initiation, promotion, and progression stages and each stage may be a possible target for chemopreventive agents. A significant outcome of these investigations on the elucidation of molecular and cellular mechanisms is the explication of signal transduction pathways induced by tumor promoters in cancer development. The current belief today is that cancer may be prevented or treated by targeting specific cancer genes, signaling proteins, and transcription factors. The molecular mechanisms explaining how normal cells undergo neoplastic transformation induced by tumor promoters are rapidly being clarified. Accumulating research evidence suggests that many of dietary factors, including tea compounds, may be used alone or in combination with traditional chemotherapeutic agents to prevent or treat cancer. The potential advantage of many natural or dietary compounds seems to focus on their potent anticancer activity combined with low toxicity and very few adverse side effects. This review summarizes some of our recent work regarding the effects of the various tea components on signal transduction pathways involved in neoplastic cell transformation and carcinogenesis. © 2006 Wiley‐Liss, Inc.
Use of tissue water as a concentration reference for proton spectroscopic imaging
Authors: Gasparovic Charles , Song Tao , Devier Deidre , Bockholt H. Jeremy , Caprihan Arvind , Mullins Paul G. , Posse Stefan , Jung Rex E. , Morrison Leslie A. 
Published: May 2006

AbstractA strategy for using tissue water as a concentration standard in 1H magnetic resonance spectroscopic imaging studies on the brain is presented, and the potential errors that may arise when the method is used are examined. The sensitivity of the method to errors in estimates of the different water compartment relaxation times is shown to be small at short echo times (TEs). Using data from healthy human subjects, it is shown that different image segmentation approaches that are commonly used to account for partial volume effects (SPM2, FSL's FAST, and K‐means) lead to different estimates of metabolite levels, particularly in gray matter (GM), owing primarily to variability in the estimates of the cerebrospinal fluid (CSF) fraction. While consistency does not necessarily validate a method, a multispectral segmentation approach using FAST yielded the lowest intersubject variability in the estimates of GM metabolites. The mean GM and white matter (WM) levels of N‐acetyl groups (NAc, primarily N‐acetylaspartate), choline (Ch), and creatine (Cr) obtained in these subjects using the described method with FAST multispectral segmentation are reported: GM [NAc] = 17.16 ± 1.19 mM; WM [NAc] = 14.26 ± 1.38 mM; GM [Ch] = 3.27 ± 0.47 mM; WM [Ch] = 2.65 ± 0.25 mM; GM [Cr] = 13.98 ± 1.20 mM; and WM [Cr] = 7.10 ± 0.67 mM. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.
Estrogen induced functional hypertrophy and increased force generation of the female rabbit bladder
Authors: Lin Alpha Dian‐Yu , Levin Robert , Kogan Barry , Whitbeck Catherine , Chichester Paul , Sokol Rebekah , Mannikarottu Anita 
Published: May 2006

AbstractAimsEstrogen is essential for physiological maintenance of the female urogenital tract. It is believed that alterations in female sex hormones play a major role in the etiology and response to urinary tract dysfunctions. In animal studies, ovariectomy (Ovx) results in smooth muscle (SM) weakness and atrophy whereas estrogen supplementation reverses these effects. Our study seeks to establish the mechanisms by which estrogen augmentation results in increased contractility.MethodsTwenty New Zealand White female rabbits were separated into five groups of four each. Group 1 served as control, rabbits of groups 2–5 were ovariectomized, group 2 ovariectomized received no estradiol, groups 3–5 were given 17‐β estradiol (1 mg/kg/day) by subcutaneous slow release tablet implant for 1, 3, and 7 days, respectively, beginning 2 weeks after Ovx. At the end of the experimental period, each rabbit was anesthetized and the urinary bladder was removed for contractile, histological, and biochemical studies.ResultsOvx resulted in significantly decreased bladder contractile function, whereas bladders tested after estradiol administration showed increased contractility. Ovx resulted in a decrease in SM/collagen ratio, whereas estrogen resulted in an increase. The estrogen receptor (ER) density significantly increased following Ovx. After 1 day of estrogen treatment, the ER density decreased significantly below control levels, but rose progressively during the estrogen treatment.ConclusionThe present study demonstrates that estrogen supplementation mediates a “functional hypertrophy,” that is a hypertrophy characterized by increased contractile responses to all forms of stimulation, and an increased ratio of SM/collagen. Neurourol. Urodynam. © 2006 Wiley‐Liss, Inc.
Once and again: Retinoic acid signaling in the developing and regenerating olfactory pathway
Authors: Rawson N.E. , LaMantia A.‐S. 
Published: May 2006

AbstractRetinoic acid (RA), a member of the steroid/thyroid superfamily of signaling molecules, is an essential regulator of morphogenesis, differentiation, and regeneration in the mammalian olfactory pathway. RA‐mediated teratogenesis dramatically alters olfactory pathway development, presumably by disrupting retinoid‐mediated inductive signaling that influences initial olfactory epithelium (OE) and bulb (OB) morphogenesis. Subsequently, RA modulates the genesis, growth, or stability of subsets of OE cells and OB interneurons. RA receptors, cofactors, and synthetic enzymes are expressed in the OE, OB, and anterior subventricular zone (SVZ), the site of neural precursors that generate new OB interneurons throughout adulthood. Their expression apparently accommodates RA signaling in OE cells, OB interneurons, and slowly dividing SVZ neural precursors. Deficiency of vitamin A, the dietary metabolic RA precursor, leads to cytological changes in the OE, as well as olfactory sensory deficits. Vitamin A therapy in animals with olfactory system damage can accelerate functional recovery. RA‐related pathology as well as its potential therapeutic activity may reflect endogenous retinoid regulation of neuronal differentiation, stability, or regeneration in the olfactory pathway from embryogenesis through adulthood. These influences may be in register with retinoid effects on immune responses, metabolism, and modulation of food intake. © 2006 Wiley Periodicals, Inc. J Neurobiol 66: 653–676, 2006
Overview of retinoid metabolism and function
Authors: Blomhoff Rune , Blomhoff Heidi Kiil 
Published: May 2006

AbstractRetinoids (vitamin A) are crucial for most forms of life. In chordates, they have important roles in the developing nervous system and notochord and many other embryonic structures, as well as in maintenance of epithelial surfaces, immune competence, and reproduction. The ability of all‐trans retinoic acid to regulate expression of several hundred genes through binding to nuclear transcription factors is believed to mediate most of these functions. The role of all‐trans retinoic may extend beyond the regulation of gene transcription because a large number of noncoding RNAs also are regulated by retinoic acid. Additionally, extra‐nuclear mechanisms of action of retinoids are also being identified. In organisms ranging from prokaryotes to humans, retinal is covalently linked to G protein‐coupled transmembrane receptors called opsins. These receptors function as light‐driven ion pumps, mediators of phototaxis, or photosensory pigments. In vertebrates phototransduction is initiated by a photochemical reaction where opsin‐bound 11‐cis‐retinal is isomerized to all‐trans‐retinal. The photosensitive receptor is restored via the retinoid visual cycle. Multiple genes encoding components of this cycle have been identified and linked to many human retinal diseases. Central aspects of vitamin A absorption, enzymatic oxidation of all‐trans retinol to all‐trans retinal and all‐trans retinoic acid, and esterification of all‐trans retinol have been clarified. Furthermore, specific binding proteins are involved in several of these enzymatic processes as well as in delivery of all‐trans retinoic acid to nuclear receptors. Thus, substantial progress has been made in our understanding of retinoid metabolism and function. This insight has improved our view of retinoids as critical molecules in vision, normal embryonic development, and in control of cellular growth, differentiation, and death throughout life. © 2006 Wiley Periodicals, Inc. J Neurobiol 66: 606–630, 2006
Retinoids and spinal cord development
Authors: Maden Malcolm 
Published: May 2006

AbstractThe role that RA plays in the development and patterning of the spinal cord is discussed. The morphogenetic process of neurulation is described in which RA plays a role because in the absence of RA signaling spina bifida results. Following neural induction, RA is involved in several patterning events in the spinal cord. It is one of the posteriorizing factors along with FGFs and Wnts and as such patterns the cervical spinal cord acting via the Hoxc transcription factors. It is involved in the induction of neural differentiation via genes such as NeuroM. It plays a part in patterning the dorsoventral axis of the anterior spinal cord where it interacts with FGF, Shh, and BMPs and induces an interneuronal population of neurons called V0 and V1 and a subset of motor neurons known as LMCs. To perform these actions RA is synthesized in the adjacent paraxial mesoderm by the enzyme RALDH2 and acts in a paracrine fashion on the developing neural tube. In the final action of RA, it begins to be synthesized within the neural tube at brachial and lumbar levels in the LMCs. Later‐born neurons migrate through this RALDH2‐expressing region and induce differentiation in these migrating neurons, which become a subset of LMC neurons known as LMCls. Thus RA acts several times over in the development of the spinal cord and not on the cells in which it is synthesized, but in adjacent cells in a paracrine manner. © 2006 Wiley Periodicals, Inc. J Neurobiol 66: 726–738, 2006
Retinoic acid and hindbrain patterning
Authors: Glover Joel C. , Renaud Jean‐Sébastien , Rijli Filippo M. 
Published: May 2006

AbstractRetinoid signaling plays an important role in the developmental patterning of the hindbrain. Studies of the teratogenic effects of retinoids showed early on that the hindbrain suffered patterning defects in cases of retinoid excess or deficiency. Closer examination of these effects in animal models suggested that retinoids might play a physiological role in specifying the antero‐posterior axis of the hindbrain. This idea was supported by the localization of retinoid synthetic and degradative enzymes, binding proteins, and receptors to the hindbrain and neighboring regions of the neuroepithelium and the mesoderm. In parallel, it became clear that the molecular patterning of the hindbrain, in terms of the regionalized expression ofHoxgenes and other developmental regulatory genes, is profoundly influenced by retinoid signaling. © 2006 Wiley Periodicals, Inc. J Neurobiol 66: 705–725, 2006
Dielectric and spectroscopic properties of PbO–Nb2O5–P2O5:V2O5 glass system
Authors: Krishna Mohan N. , Sahaya Baskaran G. , Veeraiah N. 
Published: May 2006

AbstractPbO–Nb2O5–P2O5 glasses containing different concentrations of V2O5 ranging from 0 to 1.0 mol% were prepared. A number of studies, viz. differential thermal analysis, infrared, optical absorption, Raman and ESR spectra and dielectric properties (dielectric constant ϵ′, loss tan δ, a.c. conductivity σac over a range of frequency and temperature), of these glasses have been carried out. The results have been analysed in the light of different oxidation states of vanadium ions. The analysis indicates that when the concentration of V2O5 is increased gradually, vanadium ions are observed to exist mostly in the V4+ state, occupy network‐modifying positions and decrease the rigidity of the glass network. A transformation of NbO4 to NbO6 structural units and a decrease in the concentration of PO4 structural units have also been observed with an increase in the concentration of V2O5 in the glass network. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Deterioration of MOVPE InN films on sapphire during growth and post‐growth annealing
Authors: Miwa Hiroshi , Hashimoto Akihiro , Yamamoto Akio 
Published: May 2006

AbstractThe deterioration of MOVPE InN during the growth and the post‐growth annealing processes is investigated. Photoluminescence (PL) measurement with excitation sources with a different wavelength is mainly used to detect deterioration of InN. This is aimed to get in‐depth information about the quality of InN since the penetration depth of an excitation source is different depending on its wavelength. A serious deterioration, which is the decomposition of InN, is found for InN annealed in the NH3 flow after the growth. The deterioration occurs predominantly near the substrate interface. On the contrary, the deterioration of InN during growth is scarcely observed. Since the InN films grown on sapphire have an In‐polarity, the deterioration during the post‐growth annealing occurs at the N‐surface. Such deterioration is suppressed by the supply of TMI together with NH3 (InN growth mode). From these facts, hydrogen produced by the decomposition of NH3 seems to be responsible for the deterioration since hydrogen is consumed to form CH4 when TMI is supplied. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Electrical and recombination properties and deep traps spectra in MOCVD ELOG GaN layers
Authors: Lee In‐Hwan , Polyakov A. Y. , Smirnov N. B. , Govorkov A. V. , Markov A. V. , Pearton S. J. 
Published: May 2006

AbstractElectrical properties, deep levels spectra, spectra of microcathodoluminescence, diffusion lengths of minority carriers were studied in undoped GaN films grown by standard metallorganic chemical vapour deposition on sapphire and by the epitaxial lateral overgrowth technique (ELOG). It is shown that the total concentrations of shallow donors and of electron and hole traps are very considerably lower in the ELOG material compared to the ordinary MOCVD samples. MCL and electron beam induced current EBIC imaging of ELOG samples suggests that the dislocation density in the overgrown regions is on the order of 106 cm–2 while in‐between these regions it is similar to the dislocation density in the standard material, about 109 cm–2. Local diffusion lengths were shown to follow the same trend as dislocation densities. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Real time spectroscopic ellipsometry investigation of homoepitaxial GaN grown by plasma assisted molecular beam epitaxy
Authors: Kim Tong‐Ho , Choi Soojeong , Wu Pae , Brown April , Losurdo Maria , Giangregorio Maria M. , Bruno Giovanni , Moto Akihiro 
Published: May 2006

AbstractThe growth of GaN by plasma assisted molecular beam epitaxy on GaN template substrates (GaN on sapphire) is investigated with in‐situ multi‐channel spectroscopic ellipsometry. Growth is performed under various Ga/N flux ratios at growth temperatures in the range 710–780 °C. The thermal roughening of the GaN template caused by decomposition of the surface is investigated through the termporal variation of the GaN pseudodielectric function over the temperature range of 650 °C to 850 °C. The structural, morphological, and optical properties are also discussed. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)