bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of aggressive thyroid cancer with an oncolytic herpes virus
Authors: Yu Zhenkun , Eisenberg David P. , Singh Bhuvanesh , Shah Jatin P. , Fong Yuman , Wong Richard J. 
Published: June 2004

AbstractAlthough many thyroid cancers carry a favorable prognosis, there is a subgroup of patients with more aggressive histologies. Current therapies offer no significant survival benefit to patients with anaplastic thyroid carcinomas, which are considered fatal. Oncolytic herpes simplex viruses (HSVs) have potent antitumor effects against a variety of human malignancies. We assessed the activity of a replication‐competent, attenuated, oncolytic HSV (NV1023) against 7 different thyroid cancers, including one papillary (NPA‐187), one follicular (WRO82‐1), one medullary (DRO81‐1) and 4 anaplastic (DRO90‐1, ARO, KAT‐4C and KAT‐18) cell lines. Only the follicular WRO82‐1 line was resistant to NV1023 infection and cell lysis at a concentration of 5 viral pfu per cell (MOI 5). All other cell lines at MOI 5 demonstrated >95% infection in vitro at day 2 by X‐gal staining and >88% cell death at day 4 by cytotoxicity assays. Even at MOI 0.1, 4 of these lines displayed complete cell death by day 7. Viral proliferation assays revealed that all of the nonfollicular cell lines supported logarithmic viral replication. Flank tumors of NPA‐187, DRO81‐1, DRO90‐1 and ARO in athymic nude mice were treated with NV1023 (2 × 107 pfu). All NPA‐187 tumors completely regressed following a single dose. DRO81‐1 tumors demonstrated partial response with a single dose and significant improvement with 3 serial doses. ARO and DRO90‐1 tumors showed a significant response following either single injection (54 ± 22 and 292 ± 138 mm3, respectively) or 3 serial injections (33 ± 14 and 241 ± 68 mm3, respectively) compared to saline injections (472 ± 193 and 1,257 ± 204 mm3, respectively) at day 20. These data suggest that herpes oncolytic therapy may be effective for the treatment of aggressive thyroid carcinomas and merits further investigation. © 2004 Wiley‐Liss, Inc.
Transgenic overexpression of a dominant negative mutant of FADD that, although counterselected during tumor progression, cooperates in L‐myc‐induced tumorigenesis
Authors: Hueber Anne‐Odile , Bösser Susanne , Zörnig Martin 
Published: June 2004

AbstractActivation of the so‐called death receptors, e.g., CD95/Fas/Apo‐1, is a potent stimulus to trigger apoptosis. Overexpression of the C‐terminal FADD deletion mutant FADD‐DN blocks death receptor–induced apoptosis, but despite this antiapoptotic activity, lck FADD‐DN transgenic mice do not develop lymphomas. To analyze whether functional inactivation of FADD cooperates with Myc overexpression in tumorigenesis, lck FADD‐DN transgenic mice were crossed with Eμ L‐myc transoncogenic animals. While no tumors were detected in single transgenic FADD‐DN or L‐myc mice within 15 months, 5 of 17 (29%) FADD‐DN/L‐myc double transgenic animals developed lymphomas with an average latency period of 47 weeks. Protein analysis of FADD‐DN/L‐myc tumors showed, however, undetectable levels of FADD‐DN protein. FADD‐DN protein expression was again lost in 16 of 17 FADD‐DN/p53 k.o. T‐cell lymphomas, though no significant acceleration of tumorigenesis in P53‐deficient lck FADD‐DN mice compared to p53 k.o. animals was observed. These data suggest a strong counterselection against the FADD‐DN protein during tumor progression, which could be explained by the cell cycle inhibitory activity of FADD‐DN. Such counterselection would have to be compensated for by other antiapoptotic mutations, and indeed, strong upregulation of the antiapoptotic Bcl‐2 family member Bcl‐xL was found in one of the tumors. This in vivo mouse model demonstrates that an antiapoptotic protein involved in the onset of tumorigenesis is selected against and consequently lost during tumor progression because of its additional antiproliferative activity. © 2004 Wiley‐Liss, Inc.
Role of reactive oxygen species in the induction of apoptosis by α‐tocopheryl succinate
Authors: Kang Young‐Hwa , Lee Eunmyong , Choi Moon‐Kyung , Ku Ja‐Lok , Kim So Hee , Park Yong‐Geun , Lim Soo‐Jeong 
Published: June 2004

Abstractα‐Tocopheryl succinate (TOS), a vitamin E analog, is a promising anticancer agent due to its abilities to inhibit proliferation and to induce apoptosis in a variety of human malignant cell lines, while being relatively less active toward normal cells. However, the molecular mechanisms underlying the apoptotic effects of TOS are not precisely understood. Reports that TOS can generate reactive oxygen species (ROS) prompted us to investigate the role of ROS in TOS‐induced apoptosis in cancer cells. We found that the human lung cancer A549 and H460 cell lines were much more sensitive to TOS‐induced apoptosis than the human glioblastoma T98G and U87MG cell lines. Our data suggested that the differential TOS sensitivity was not caused by differences in the uptake and retention of TOS between TOS‐sensitive and –resistant cancer cells. The differential ability of cancer cells to generate ROS in response to TOS appears to be an important factor in determining the susceptibility of cells to TOS‐induced apoptosis. Our results further suggest that TOS‐induced generation of ROS is involved in caspase‐independent apoptosis. Taken together, our findings suggest an important role of ROS generation in TOS‐induced, caspase‐independent apoptosis of cancer cells. © 2004 Wiley‐Liss, Inc.
Genetic background markedly influences vulnerability of the hippocampal neuronal organization in the “twitcher” mouse model of globoid cell leukodystrophy
Authors: Tominaga Kumiko , Matsuda Junko , Kido Makiko , Naito Etsuo , Yokota Ichiro , Toida Kazunori , Ishimura Kazunori , Suzuki Kunihiko , Kuroda Yasuhiro 
Published: June 2004

AbstractThe twitcher mouse is well known as a naturally occurring authentic mouse model of human globoid cell leukodystrophy (GLD; Krabbe disease) due to genetic deficiency of lysosomal galactosylceramidase. The twitcher mice used most commonly are on the C57BL/6J background. We generated twitcher mice that were on the mixed background of C57BL/6J and 129SvEv, the standard strain for production of targeted mutations. Twitcher mice on the mixed background were smaller and had a shorter lifespan than were those on the C57BL/6J background. Many twitcher mice on the mixed background developed generalized seizures around 30 days that were never seen in twitcher mice on the C57BL/6J background. Neuropathologically, although the degree of the typical demyelination with infiltration of macrophages was similar in the central and peripheral nervous systems, in both strains, marked neuronal cell death was observed only in twitcher mice on the mixed background. In the hippocampus, the neuronal cell death occurred prominently in the CA3 region in contrast to the relatively well‐preserved CA1 and CA2 areas. This neuropathology has never been seen in twitcher mice on the C57BL/6J background. Biochemically, the brain of twitcher mice on the mixed background showed much greater accumulation of lactosylceramide. Genetic background must be carefully taken into consideration when phenotype of mutant mice is evaluated, particularly because most targeted mutants are initially on a mixed genetic background and gradually moved to a pure background. These findings also suggest an intriguing possibility of important function of some sphingolipids in the hippocampal neuronal organization and maintenance. © 2004 Wiley‐Liss, Inc.
Antisense peptide nucleic acid targeting GluR3 delays disease onset and progression in the SOD1 G93A mouse model of familial ALS
Authors: Rembach Alan , Turner Bradley J. , Bruce Stephen , Cheah Irwin K. , Scott Rachel L. , Lopes Elizabeth C. , Zagami Chrissandra J. , Beart Philip M. , Cheung Nam S. , Langford Steven J. , Cheema Surindar S. 
Published: June 2004

AbstractGlutamate excitotoxicity is strongly implicated as a major contributing factor in motor neuron degeneration in amyotrophic lateral sclerosis (ALS). Excitotoxicity results from elevated intracellular calcium ion (Ca2+) levels, which in turn recruit cell death signaling pathways. Recent evidence suggests that α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) receptor subunit (GluR) stoichiometry is a dominant factor leading to excess Ca2+ loading in neurodegeneration. In particular, the Ca2+ permeable glutamate receptor subunit 3 (GluR3) has been implicated in several neurologic conditions such as bipolar disorder and epilepsy. Recent proteomic analysis within our group on the copper zinc superoxide dismutase (SOD1)G93A transgenic mouse model of familial ALS (FALS) reveals a potentially deleterious upregulation of GluR3 in spinal cord compared to that in wild‐type littermates. Based on this finding we designed a 12mer antisense peptide nucleic acid (PNA) directed against GluR3. This sequence significantly reduced levels of GluR3 protein and protected neuroblastoma × spinal cord (NSC‐34) cells against death induced by the AMPA receptor‐specific agonist (S)‐5‐fluorowillardiine. We subsequently treated SOD1G93A mice thrice weekly with intraperitoneal injections of the antisense PNA (2.5 mg/kg) commencing at postnatal day 50. Mice treated with the antisense sequence had significantly extended survival compared to mice injected with a nonsense sequence. Western blot analysis, however, did not reveal a significant reduction in GluR3 protein levels in whole extracts of the lumbar spinal cord. These results suggest that interference with the GluR3 component of the AMPA receptor assembly may be a novel strategy for controlling excitotoxic destruction of motor neurons and may lead to new therapeutic opportunities for the treatment of human ALS. © 2004 Wiley‐Liss, Inc.
Food deprivation decreases responsiveness of ventromedial hypothalamic neurons to melanocortins
Authors: Li Y.Z. , Davidowa H. 
Published: June 2004

AbstractThe melanocortin system is involved in regulation of food intake and energy balance. Melanocyte‐stimulating hormone (α‐MSH) is an endogenous melanocortin receptor (MC‐R) agonist. It acts on MC3/4 receptors to reduce appetite and to increase energy expenditure. The production of α‐MSH is reduced during food deprivation, but MC4‐R density is increased. The net effect of reduced α‐MSH production and increased receptor level is not clear. To address this question, responses of ventromedial hypothalamic (VMH) neurons to melanotan II (MTII; a synthetic analogue of α‐MSH) were recorded in brain slices from fed and food‐deprived rats. Responses to the highest dose MTII were observed in 61% of VMH neurons from fed rats but only 33% of VMH neurons from food‐deprived rats. To assess a possible mechanism by which responsiveness to melanocortins is diminished even though receptor number is augmented during fasting, we examined the effect of agouti gene‐related peptide (AGRP), an endogenous MC‐R antagonist that stimulates food intake. The synthesis of AGRP increases during fasting. AGRP significantly reduced VMH responsiveness to MTII. Additionally, AGRP by itself evoked neuronal responses, in contrast to synthetic MC‐R antagonists. AGRP (1 nM) induced a predominant inhibitory effect on VMH neurons in food‐deprived rats but not in fed rats. In the presence of AGRP, MTII induced a significant inhibition of neuronal activity in deprived rats, but not in fed rats. Inhibition of VMH neurons reduces energy expenditure and the satiety signal. These findings suggest that although food deprivation increases MC4‐R density, it nevertheless reduces the effectiveness of melanocortins on VMH neurons, possibly by the involvement of AGRP. © 2004 Wiley‐Liss, Inc.
Remote Raman spectroscopy as a prospective tool for planetary surfaces
Authors: Klein V. , Popp J. , Tarcea N. , Schmitt M. , Kiefer W. , Hofer S. , Stuffler T. , Hilchenbach M. , Doyle D. , Dieckmann M. 
Published: June 2004

AbstractThis paper summarizes the content of four Technical Notes that were established within a study contracted by the European Space Agency concerning the possibility of applying Raman spectroscopy in the field of remote imaging. An overview of the scientific demands and Raman spectroscopy from the user's point of view is provided together with a few key aspects in the field of planetary research. Laboratory Raman experiments were used for establishing a basis for the subsequent extrapolation to remote Raman spectroscopy. A detailed numerical simulator was used to derive numbers concerning link budgets and overall remote Raman spectroscopy instrument performance for a number of different scenarios. A summary of subsystem technologies and criticalities is also presented together with the necessary R&D efforts. Copyright © 2004 John Wiley & Sons, Ltd.
Raman spectroscopy of ion‐irradiated interplanetary carbon dust analogues
Authors: Baratta G. A. , Mennella V. , Brucato J. R. , Colangeli L. , Leto G. , Palumbo M. E. , Strazzulla G. 
Published: June 2004

AbstractInterplanetary dust particles (IDPs) and meteorites provide a unique opportunity to study extraterrestrial materials in the laboratory. Different Raman studies have shown that most of IDPs exhibit the characteristic amorphous carbon Raman feature. Different degrees of order have been recognized in the amorphous carbon phase of IDPs, testifying either to different origins or to different processing under different physical conditions (temperature, pressure, etc.). This paper presents a comparison between the amorphous carbon Raman features of IDPs and those of carbon dust analogues obtained in the laboratory by ion irradiation of carbon‐containing frozen gases and by arc discharge. We propose a possible mechanism able to induce an ‘evolution’ of IDPs. In particular, amorphous carbon with different degrees of order could be indicative of different irradiation doses by solar wind particles and fast solar protons suffered by IDPs in the interplanetary medium before collection in the Earth's atmosphere. Copyright © 2004 John Wiley & Sons, Ltd.
Raman spectroscopy of desert varnishes and their rock substrata
Authors: Edwards Howell G. M. , Moody Caroline A. , Jorge Villar Susana E. , Mancinelli Rocco 
Published: June 2004

AbstractThe Fourier—transform Raman spectra of desert varnish specimens and their rock substrata from locations in Colorado and Nevada, USA, are reported. The Colorado specimen exhibits molecular signatures for β‐carotene and scytonemin; the latter is a characteristic biomarker of cyanobacterial colonies and is produced by these organisms in response to high UV‐radiation stress. The Nevada specimen, on the other hand, exhibited characteristic Raman bands arising from whewellite and lichen metabolites such as atranorin and paretin, indicative of an epilithic lichen colonization. The application of Raman microscopy for the identification of extinct or extant biological colonization of rocks in exposed hot desert environments could form a useful adjunct for database construction relevant to exobiological studies and key spectral bioindicators for the robotic exploration of planetary surfaces. Copyright © 2004 John Wiley & Sons, Ltd.
Biological modification of haematite in Antarctic cryptoendolithic communities
Authors: Edwards Howell G. M. , Wynn‐Williams David D. , Villar Susana E. Jorge 
Published: June 2004

AbstractDetailed FT‐Raman spectra of Antarctic cryptoendolithic colonies in Beacon sandstone have revealed some novel information about the biogeological modification process involving iron(III) mobilization by the organism. The previously unreported but characteristic orange–yellow surface colour of endolithic rock specimens is attributed to the presence of goethite, α‐FeOOH, iron(III) oxide hydroxide, which has been converted from haematite, α‐Fe2O3, by cyanobacterial modification. Although goethite is also identified in the biological layers, haematite is found unchanged elsewhere in the specimens. No spectroscopic evidence is found for iron(III) complexes of metabolic byproducts such as oxalate or pyruvate. The results are of relevance to remote spectroscopic sensing experiments for Martian planetary surface exploration, where the presence of iron(III) oxide is evident, below which it seems likely that a significant quantity of hydroxyl groups in the form of water could exist. Copyright © 2004 John Wiley & Sons, Ltd.
Protective pigmentation in UVB‐screened Antarctic lichens studied by Fourier transform Raman spectroscopy: an extremophile bioresponse to radiation stress
Authors: Edwards Howell G. M. , Cockell Charles S. , Newton Emma M. , Wynn‐Williams David D. 
Published: June 2004

AbstractFT‐Raman spectra were obtained for two Antarctic extremophiles, the epilithic lichens Xanthoria elegans and Caloplaca sublobulata from the maritime ecological long‐term research site on Leonie Island. Twelve specimens from cloches designed for the filtering out and transmission of UVB radiation over a 2 year period and two specimens from the natural habitat outside the cloches were analysed in terms of their characteristic Raman bands from the two photoprotective pigments parietin and β‐carotene. Following chemometric analysis, the specimens inside the UVB‐protective cloches exhibited a lower parietin:β‐carotene ratio than specimens from the same habitat that did not have UVB protection. The relative roles of parietin, a passive UVB photoprotectant, and β‐carotene are discussed and a possible duality of biological function is suggested for these pigments. Copyright © 2004 John Wiley & Sons, Ltd.
Raman spectroscopy of sediments from the Antarctic Dry Valleys; an analogue study for exploration of potential paleolakes on Mars
Authors: Edwards Howell G. M. , Jorge Villar Susana E. , Bishop Janice L. , Bloomfield Matthew 
Published: June 2004

AbstractA Raman spectroscopic study was performed on igneous sediments dominated by plagioclase, K‐feldspar, quartz and pyroxene from the Dry Valleys region of Antarctica. Lakes from this region of Antarctica have been investigated as possible analogues for paleolake environments on early Mars. Gaining Raman spectra of such sediments provides compositional information for missions to Mars, and also the necessary ground truthing for use of Raman spectroscopy for exploration of geology, and perhaps biology, on Mars. Sediments measured in this study were collected from the perennially ice‐covered Lake Hoare in the Taylor Valley and include surface sediments, and lakebottom sediments from oxic and anoxic zones of the lake. Micro‐Raman spectroscopy provides a unique opportunity for in situ exploration of biogeochemical processes on the micron scale at field sites. For example, in these potential paleolake analogue sediments, ∼5 µm sized sulfide deposits were observed on the surface of quartz grains in one of the anoxic sediments. Small amounts of calcite, organics, clays and iron oxides/hydroxides were also identified. Copyright © 2004 John Wiley & Sons, Ltd.
Mineralogy of a Martian meteorite as determined by Raman spectroscopy
Authors: Wang Alian , Kuebler Karla , Jolliff Bradley , Haskin Larry A. 
Published: June 2004

AbstractUsing the Raman point‐count procedure that we anticipate using in planetary surface exploration, we have identified and characterized the major, minor and trace mineral phases in rock chips of a Martian meteorite, EETA 79001. Raman spectra are shown for pyroxene, olivine, maskelynite (shocked, isotropized feldspar), chromite, magnetite, ilmenite, ulvöspinel, pyroxferroite, merrillite, apatite, anatase, an Fe sulfide, calcite and hematite. Raman spectra provide information on compositional variations of pyroxene, olivine and FeTiCr oxides and modal proportions of the rock. The maskelynite‐free mineral mode obtained on rough rock surfaces is consistent with modes obtained by optical microscopy on a thin section of lithology A of this meteorite. Compositions and variations in compositions of major silicate minerals (pyroxene and olivine) on the basis of Raman peak positions are consistent with those obtained in previous studies by electron probe microanalysis. The variations in composition of the silicate minerals represent different stages of crystallization during the formation of this rock near the Martian surface. Copyright © 2004 John Wiley & Sons, Ltd.
Comparative micro‐Raman study of the Nakhla and Vaca Muerta meteorites
Authors: Rull F. , Martinez‐Frias J. , Sansano A. , Medina J. , Edwards H. G. M. 
Published: June 2004

AbstractA comprehensive micro‐Raman spectroscopic analysis of the Nakhla and Vaca Muerta meteorites is reported. The major and minor mineral components were identified from comparison with mineralogical standards and literature databases. The compositions of pyroxenes and olivines were obtained using only this technique and correlation data between band parameters and the chemical composition of reference materials existing in the literature. The presence of calcite in both meteorite specimens was noted; its identification inside eucrite grains in the Vaca Muerta meteorite is particularly noteworthy. Their spectral parameters show strong similarities. Aragonite associated with calcite is reported for the first time in Vaca Muerta meteorite. Spectra of siderite, which appears associated with clinopyroxenes, are also reported in Nakhla meteorite. Iron oxides were analysed in detail in both meteorites. Magnetite is the main oxide phase observed in Nakhla and goethite, lepidocrocite and magnetite in Vaca Muerta. In both cases haematite was not observed. A comparison of the spectral parameters of these mineral phases observed in both meteorites was made and their possible origin as secondary minerals is discussed. This study stresses the potential of Raman spectroscopy in the mineralogical characterization of meteorites on a very small scale and also the potential applications of Raman spectroscopy for use on landers or rovers on the surface of Mars or other planetary bodies. Copyright © 2004 John Wiley & Sons, Ltd.
The role of Raman spectroscopy as an astrobiological tool in the exploration of Mars
Authors: Ellery Alex , Wynn‐Williams David , Parnell John , Edwards Howell G. M. , Dickensheets David 
Published: June 2004

AbstractWe describe how the exploration of the Martian environment would be considerably enhanced through the use of Raman spectroscopy. Furthermore, Raman spectroscopy is particularly suited for both mineralogical analysis of Martian rock and soil and for the detection of fossilised biota from former Martian micro‐organisms. We outline astrobiologically relevant features of the Martian environment and issues related to the detection of biotic residues. We further discuss the possibility of the emergence of photosynthetic bacteria on early Mars which may have left fossil evidence. We describe how Raman spectroscopy may be deployed for both astrobiological and mineralogical investigation, particularly in search of pigmented biomolecules, and describe the requirements for a spaceflight‐qualified version of a Raman spectrometer for deployment on Mars. Copyright © 2004 John Wiley & Sons, Ltd.
Micro‐Raman spectroscopy: a valuable tool for the investigation of extraterrestrial material
Authors: Hochleitner R. , Tarcea N. , Simon G. , Kiefer W. , Popp J. 
Published: June 2004

AbstractThe investigation of different samples of SNC (Shergotty–Nakhla–Chassigny) meteorites was chosen to test the ability of micro‐Raman spectroscopy to cope with extraterrestrial material. The following SNC meteorites were investigated: Sayh al Uhaymir 060, Dar al Gani 735, Dar al Gani 476, Northwest Africa 856, Los Angeles, Northwest Africa 1068 and Zagami. Pyrite as a hitherto undescribed phase in the picritic (olivine‐phyric) shergottite NWA 1068 and reduced carbon (e.g. graphite) and anatase in the shergottite Say al Uhaymir 060 are new findings for this class of meteorites. Copyright © 2004 John Wiley & Sons, Ltd.