bluuebunny/crossref_metadata_2025_split huggingface dataset:
The synthetic retinoid RO 13‐6307 induces neuroblastoma differentiation in vitro and inhibits neuroblastoma tumour growth in vivo
Authors: Ponthan Frida , Johnsen John Inge , Klevenvall Lena , Castro Juan , Kogner Per 
Published: February 2003

AbstractRetinoids modulate cell proliferation, differentiation and apoptosis in a variety of tumour cells including leukaemia and neuroblastoma, a childhood tumour of the sympathetic nervous system. 13‐cis retinoic acid is in clinical use against minimal residual disease in neuroblastoma, where the effect seems to depend on dose, scheduling and tumour mass. Novel retinoids are searched for, to improve potency and lower toxicity. We investigated the effect of the synthetic retinoid Ro 13‐6307 on neuroblastoma growth in vitro on SK‐N‐BE(2) and SH‐SY5Y cells. Furthermore, effects on tumour growth and the toxicity profile were investigated in a rat xenograft model. Effects of Ro 13‐6307 were compared to 13‐cis RA (retinoic acid) in vitro and in vivo. Neuroblastoma cells treated with 1 μM Ro 13‐6307 exhibited neuronal differentiation, decreased proliferation and accumulation of cells in G1 phase in at least the same magnitude as 5 μM 13‐cis RA. No apoptosis was detected in vitro. Treatment of nude rats with neuroblastoma using Ro 13‐6307, 0.12 mg p.o. daily, decreased neuroblastoma growth in vivo, in terms of tumour volume during treatment and tumour weight at sacrifice (p < 0.05). In contrast, Ro 13‐6307, 0.08 mg p.o. daily, resulted in no significant reduction in tumour growth. All rats treated with Ro 13‐6307 gained less weight than control rats, but they exhibited no other signs of toxicity. The toxicity profile of Ro 13‐6307 was similar to what we found with 13‐cis RA. Our preclinical results suggest that Ro 13‐6307 may be a candidate retinoid for clinical oral therapy of neuroblastoma in children. © 2003 Wiley‐Liss, Inc.
Role of IRF‐1 and caspase‐7 in IFN‐γ enhancement of Fas‐mediated apoptosis in ACHN renal cell carcinoma cells
Authors: Tomita Yoshihiko , Bilim Vladimir , Hara Noboru , Kasahara Takashi , Takahashi Kota 
Published: February 2003

AbstractCaspases exist as zymogens, and are activated by various extracellular stimuli, leading to apoptosis. One such stimulus is Fas/CD95, a member of the tumor necrosis factor receptor family, providing one means of cytotoxic T lymphocyte (CTL)‐mediated cell lysis. Clinical evidence has shown that administration of cytokine leads to regression in selected patients with renal cell carcinomas (RCCs). Interferon‐γ (IFN‐γ) indicates its contribution to anti‐tumor activity of immune cells. IFN‐γ elicits its effect through the transcription factor signal transducer and activator of transcription‐1 (STAT‐1), and through interferon regulatory factor‐1 (IRF‐1), one of the target genes of STAT‐1. Our previous study demonstrated an increase in the susceptibility of ACHN cells, established from RCC, to Fas‐mediated apoptosis by IFN‐γ, and the inhibition of this effect by the caspase‐3 and ‐7 inhibitor, DEVD‐CHO. We demonstrated the following phenomena in IFN‐γ‐treated ACHN cells: 1) enhanced transcription of caspase‐1, 3 and 7 mRNAs without any change in cleavage of their substrates; 2) increased cleavage DEVD (specific for caspase‐3 and 7), but not YVAD (for caspase‐1) or DMQD (for caspase‐3), after anti‐Fas/CD95 MAb treatment; 3) activation of the STAT‐1 and IRF‐1 pathway; and 4) partial abrogation of the IFN‐γ‐induced increase in Fas‐mediated apoptosis by antisense IRF‐1 oligodeoxynucleotide. These results suggest that IRF‐1 plays a pivotal role in the IFN‐γ‐mediated‐enhancement of Fas/CD95‐mediated apoptosis, through regulation of DEVD‐CHO‐sensitive caspases, most likely caspase‐7. © 2003 Wiley‐Liss, Inc.
Treatment of colon and breast carcinoma cells with 5‐fluorouracil enhances expression of carcinoembryonic antigen and susceptibility to HLA‐A(*)02.01 restricted, CEA‐peptide‐specific cytotoxic T cells in vitro
Authors: Correale Pierpaolo , Aquino Angelo , Giuliani Antonio , Pellegrini Monia , Micheli Lucia , Cusi Maria Grazia , Nencini Cristina , Petrioli Roberto , Prete Salvatore , De Vecchis Liana , Turriziani Mario , Giorgi Giorgio , Bonmassar Enzo , Francini Guido 
Published: February 2003

AbstractCancer vaccines directed against tumor associate antigen (TAA) have produced encouraging results in preclinical models but not in cancer patients. A major limitation of this strategy is the relative degree of tolerance to these antigens and the low and heterogeneous tumor cell expression of TAA and major histocompatibility complex (MHC). Previous studies have shown that 5‐fluorouracil (5‐FU) can upregulate the expression of membrane‐associated carcino‐embryonic antigen (CEA), and MHC molecules in colon and breast carcinoma cell lines. We have investigated whether this drug can also enhance their sensitivity to the lytic effects of CEA‐peptide specific Cytotoxic T cell lymphocytes (CTL). The CEA peptide‐specific CTLs generated in our laboratory from normal HLA‐A(*)02.01+ donor PBMCs, were able to kill HLA‐A(*)02.01+/CEA+ breast (MCF‐7‐T103) and colon (HLA‐A(*)02.01 gene‐transfected HT‐29 and C22.20) carcinoma cells in HLA‐A(*)02.01 restricted manner. The treatment of target cells with 5‐FU, enhanced their CEA expression and susceptibility to CTL‐mediated lysis. Cold competition assays confirmed these results, thus supporting the hypothesis that immune target cell lysis and 5‐FU mediated enhancement were dependent on CEA peptide presentation by cancer cells. 5‐FU treatment of functionally “mature” CTL after in vitro expansion, did not reduce their cytolytic activity against MT‐2 target cells but, when the anti‐metabolite was added during the immune‐sensitization phase, CTL generation was significantly inhibited. These results provide a rationale for investigating a possible new role of 5‐FU as an immuno targeting amplifier agent in breast and colorectal cancer patients immunized with CEA‐directed cancer vaccines. © 2003 Wiley‐Liss, Inc.
C‐Raf controlled pathways in the protection of tumor cells from apoptosis
Authors: Slater Emily P. , Stübig Thomas , Lau Quek Choon , Achenbach Tatjana V. , Rapp Ulf R. , Müller Rolf 
Published: February 2003

AbstractThe Raf serine‐threonine kinase is upregulated in many human tumors and plays a pivotal role in tumor cell proliferation and survival. Abrogation of c‐Raf expression by specific antisense oligonucleotides (Raf‐AS‐ODN) efficiently blocks tumor cell growth and induces apoptosis in human cancer cells. The signaling pathways and molecular mechanisms c‐Raf utilizes to mediate the survival of tumor cells are, however, not well understood. Here we show that apoptosis triggered by Raf depletion cannot be overcome by ectopic Bcl‐2 expression and occurs in the absence of cytochrome c release, arguing against a direct impact of c‐Raf on mitochondrial pathways of apoptosis regulation. We also show that c‐Raf depletion leads to a clearly decreased expression of different epidermal growth factor (EGF) receptor ligands, suggesting that the autocrine stimulation of an EGF receptor‐mediated survival pathway might be involved in the blockade of tumor cell apoptotis by c‐Raf. © 2003 Wiley‐Liss, Inc.
Lack of serological evidence for an association between simian virus 40 and lymphoma
Authors: de Sanjose Silvia , Shah Keerti V. , Domingo‐Domenech Eva , Engels Eric A. , Fernandez de Sevilla Alberto , Alvaro Tomas , Garcia‐Villanueva Mercedes , Romagosa Vicens , Gonzalez‐Barca Eva , Viscidi Raphael P. 
Published: February 2003

AbstractRecent studies have implicated simian virus 40 (SV40) in non‐Hodgkin's lymphomas based on detection of SV40 DNA sequences. We employed a virus‐like‐particle (VLP)‐based enzyme immunoassay for antibodies to SV40 to test sera from 520 lymphoma cases and 587 controls in Spain. The SV40 seroprevalence was 9.5% in controls and 5.9% in cases. Antibody levels of the positive sera were low. There was no association of SV40 seropositivity with any subtype of lymphoma. VLPs of the human BK virus substantially inhibited the SV40 reactivity of human sera. There was no serological evidence of widespread SV40 infection and no association of SV40 seropositivity with human lymphomas in Spain. © 2003 Wiley‐Liss, Inc.
Equitable resolvable coverings
Authors: van Dam Edwin R. , Haemers Willem H. , Peek Maurice B. M. 
Published: February 2003

AbstractIn an earlier article, Willem H. Haemers has determined the minimum number of parallel classes in a resolvable 2‐(qk,k,1) covering for all k ≥ 2 and q = 2 or 3. Here, we complete the case q = 4, by construction of the desired coverings using the method of simulated annealing. Secondly, we look at equitable resolvable 2‐(qk,k,1) coverings. These are resolvable coverings which have the additional property that every pair of points is covered at most twice. We show that these coverings satisfy k < 2q −  $\sqrt{2q - {9\over4}}$, and we give several examples. In one of these examples, k > q. © 2003 Wiley Periodicals, Inc. J Combin Designs 11: 113–123, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jcd.10024
On DRC‐covering of Kn by cycles
Authors: Bermond Jean‐Claude , Coudert David , Yu Min‐Li 
Published: February 2003

AbstractThis paper considers the cycle covering of complete graphs motivated by the design of survivable WDM networks, where the requests are routed on INF‐networks which are protected independently from each other. The problem can be stated as follows: for a given graph G, find a cycle covering of the edge set of Kn, where V(Kn) = V(G), such that each cycle in the covering satisfies the disjoint routing constraint (DRC7rpar;, relatively to G, which can be stated as follows: to each edge of Kn we associate in G a path and all the paths associated to the edges of a cycle of the covering must be vertex disjoint. Here we consider the case where G = Cn, a ring of size n and we want to minimize the number of cycles in the covering. We give optimal solutions for the problem as well as for variations of the problem, namely, its directed version and the case when the cycle length is fixed to 4. © 2003 Wiley Periodicals, Inc. J Combin Designs 11: 100–112, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jcd.10040
Structure theorem for tournaments omitting N5
Authors: Latka Brenda J. 
Published: February 2003

AbstractA finite tournament T is tight if the class of finite tournaments omitting T is well‐quasi‐ordered. We show here that a certain tournament N5 on five vertices is tight. This is one of the main steps in an exact classification of the tight tournaments, as explained in [10]; the third and final step is carried out in [11]. The proof involves an encoding of the indecomposable tournaments omitting N5 by a finite alphabet, followed by an application of Kruskal's Tree Theorem. This problem arises in model theory and in computational complexity in a more general form, which remains open: the problem is to give an effective criterion for a finite set {T1,…,Tk} of finite tournaments to be tight in the sense that the class of all finite tournaments omitting each of T1,…,Tk is well‐quasi‐ordered. © 2003 Wiley Periodicals, Inc. J Graph Theory 42: 165–192, 2003
Coloring with three‐colored subgraphs
Authors: Mubayi Dhruv 
Published: February 2003

AbstractLet f(n) be the minimum number of colors required to color the edges of Kn,n such that every copy of K3,3 receives at least three colors on its edges. We prove that

$$(0.62+o(1))\sqrt{n}< \, f(n)< \, (1+o(1))\sqrt{n}$$,

where the upper bound is obtained by an explicit edge‐coloring. This complements earlier results of Axenovich, Füredi, and Mubayi [1]. © 2003 Wiley Periodicals, Inc. J Graph Theory 42: 193–198, 2003
Degree conditions for k‐ordered hamiltonian graphs
Authors: Faudree Ralph J. , Gould Ronald. J. , Kostochka Alexandr V. , Lesniak Linda , Schiermeyer Ingo , Saito Akira 
Published: February 2003

AbstractFor a positive integer k, a graph G is k‐ordered hamiltonian if for every ordered sequence of k vertices there is a hamiltonian cycle that encounters the vertices of the sequence in the given order. It is shown that if G is a graph of order n with 3 ≤ k ≤ n/2, and deg(u) + deg(v) ≥ n + (3k − 9)/2 for every pair u, v of nonadjacent vertices of G, then G is k‐ordered hamiltonian. Minimum degree conditions are also given for k‐ordered hamiltonicity. © 2003 Wiley Periodicals, Inc. J Graph Theory 42: 199–210, 2003
Degree sequence conditions for equal edge‐connectivity and minimum degree, depending on the clique number
Authors: Volkmann Lutz 
Published: February 2003

AbstractUsing the well‐known Theorem of Turán, we present in this paper degree sequence conditions for the equality of edge‐connectivity and minimum degree, depending on the clique number of a graph. Different examples will show that these conditions are best possible and independent of all the known results in this area. © 2003 Wiley Periodicals, Inc. J Graph Theory 42: 234–245, 2003
Edge list multicoloring trees: An extension of Hall's theorem
Authors: Cropper Mathew , Gyárfás András , Lehel Jenő 
Published: February 2003

AbstractWe prove a necessary and sufficient condition for the existence of edge list multicoloring of trees. The result extends the Halmos–Vaughan generalization of Hall's theorem on the existence of distinct representatives of sets. © 2003 Wiley Periodicals, Inc. J Graph Theory 42: 246–255, 2003
Tumor necrosis factor‐α regulation of insulin‐like growth factor‐I, type 1 IGF receptor, and IGF binding protein expression in cerebellum of transgenic mice
Authors: Ye Ping , Price Wayne , Kassiotis George , Kollias George , D'Ercole A. Joseph 
Published: February 2003

AbstractTumor necrosis factor‐α (TNF‐α), a proinflammatory cytokine, has been implicated in the pathogenesis of several disorders and injuries in the central nervous system (CNS). Unlike IGF‐I, which promotes CNS growth, TNF‐α causes brain growth retardation and neural damage. Recently TNF‐α has been shown to inhibit IGF‐I signaling and actions in non‐neural tissue. To investigate whether TNF‐α deleteriously influences brain growth by altering the IGF‐I system in vivo, we examined the expression of IGF‐I, the type 1 IGF receptor (IGF1R) and IGF binding proteins (IGFBPs) in the brain of transgenic (Tg) mice with murine TNF‐α overexpression. We show that overexpression of TNF‐α reduces the weights of whole brain and all brain regions examined during development. In adult TNF‐α Tg mice, cerebellum (CB) exhibited the greatest reduction in weight among the five brain regions examined, being ∼77% of that in wild‐type (WT) mice. IGF‐I abundance was decreased in the CB, as well as in cerebral cortex and diencephalon, of TNF‐α Tg mice. When compared to those in WT mice, CB IGF‐I abundance in Tg mice was reduced by ∼35%, ∼45%, and ∼40% at 2, 6, and 9 weeks of age, respectively. Of the IGFBPs studied the abundance of IGFBP‐3 and IGFBP‐4 was increased by 2–3.7‐fold, and the abundance of IGFBP‐5 was decreased by ∼3‐fold (as judged by Western immunoblot analysis). Histological analysis and immunocytochemical staining confirmed that TNF‐α specifically increases IGFBP‐3 and IGFBP‐4 immunoreactivity, as well as that of the IGF1R, in radial glial and Purkinje cells. In addition, TNF‐α alters CB cytoarchitecture, apparently by influencing granule cell migration. Our data indicate that TNF‐α alters the expression of IGF‐I system proteins in vivo, and suggest that altered expression of IGF‐I system proteins may in part explain TNF‐α deleterious actions on brain growth. © 2002 Wiley‐Liss, Inc.
Organic cation transporter capable of transporting serotonin is up‐regulated in serotonin transporter‐deficient mice
Authors: Schmitt A. , Mössner R. , Gossmann A. , Fischer I.G. , Gorboulev V. , Murphy D.L. , Koepsell H. , Lesch K.P. 
Published: February 2003

AbstractThe serotonin (5HT) transporter (5HTT) regulates serotonergic neurotransmission by mediating the reuptake of 5HT from the synaptic cleft. Although lacking the high affinity and selectivity of the 5HTT, the brain expresses a large number of other transporters, including the polyspecific organic cation transporters (OCTs). OCT1 and OCT3, members of the potential‐sensitive organic cation transporter gene family, physiologically transport a wide spectrum of organic cations. In addition, both transporters mediate low‐affinity 5HT transport and, therefore, may participate in the clearance of excessive 5HT. Because concentrations of extracellular 5HT are increased in the brain of 5HTT‐deficient mice, they are a model for investigating the role of OCTs in 5HT system homeostasis. Here, we analyzed OCT1 and OCT3 gene expression in the brain of 5HTT knockout mice by semiquantitative competitive polymerase chain reaction and in situ hybridization. We demonstrate that, in 5HTT‐deficient mice, OCT3 mRNA concentrations were significantly increased in the hippocampus, but not in other brain regions, including cortex, striatum, cerebellum, and brainstem. In contrast, no difference in OCT1 expression was detected between 5HTT knockout and control mice. Up‐regulation of OCT3 expression and enhanced low‐affinity 5HT uptake may limit the adverse effects of elevated extracellular 5HT and may play a critical role in maintaining 5HT‐dependent functions of the hippocampus in the absence of 5HTT. © 2002 Wiley‐Liss, Inc.
Thyroid hormones regulate the frequency of miniature end‐plate currents in pre‐ and prometamorphic stages of the tadpole tail
Authors: Rojas Legier V. , Bonilla Laurie , Baez Sheila , Lasalde‐Dominicci José A. 
Published: February 2003

AbstractThyroid hormones (THs), primarily 3,3′,5‐triiode‐L‐thyronine (T3), have been clearly established as natural inducers of apoptosis during metamorphosis of anuran embryos. We decided to use this phenomenon to test the hypothesis that, prior to genomic activation, T3 has acute actions in the neuromuscular junction (NMJ) of the tail of amphibian embryos. We detected a dramatic increase in the production of miniature end‐plate currents (MEPCs) 2–5 min after continuous application of T3 (250 nM) using focal recordings under voltage clamp. Furthermore, this increase in the spontaneous release of neurotransmitter, evaluated by the MEPC frequency, was maintained for several hours. Reverse‐T3, the “inhibitory” form of THs, prevented this increase in MEPC frequency, suggesting that this is probably a highly specific action of T3. In addition, the elevation in MEPC frequency induced by T3 was unchanged in the presence or absence of extracellular calcium. The T3‐mediated increase in MEPC frequency was blocked by niflumic acid, a nonsteroidal antinflammatory fenamate used to prevent the apoptotic volume decrease observed in many systems. The present study demonstrated that T3 induces a remarkable nongenomic action in the NMJ of the tadpole tail at pre‐ and promatamorphic stages. © 2002 Wiley‐Liss, Inc.
Erythropoietin prevents early and late neuronal demise through modulation of Akt1 and induction of caspase 1, 3, and 8
Authors: Chong Zhao Zhong , Lin Shi‐Hua , Kang Jing‐Qiong , Maiese Kenneth 
Published: February 2003

AbstractErythropoietin (EPO) modulates primarily the proliferation of immature erythroid precursors, but little is known of the potential protective mechanisms of EPO in the central nervous system. We therefore examined the ability of EPO to modulate a series of death‐related cellular pathways during anoxia and free radical induced neuronal degeneration. Neuronal injury was evaluated by trypan blue, DNA fragmentation, membrane phosphatidylserine exposure, protein kinase B phosphorylation, cysteine protease activity, mitochondrial membrane potential, and mitogen‐activated protein (MAP) kinase phosphorylation. We demonstrate that constitutive neuronal EPO is insufficient to prevent cellular injury, but that signaling through the EPO receptor remains biologically responsive to exogenous EPO administration. Exogenous EPO is both necessary and sufficient to prevent acute genomic DNA destruction and subsequent phagocytosis through membrane PS exposure, because neuronal protection by EPO is completely abolished by co‐treatment with an anti‐EPO neutralizing antibody. Through pathways that involve the initial activation of protein kinase B, EPO maintains mitochondrial membrane potential. Subsequently, EPO inhibits caspase 8‐, caspase 1‐, and caspase 3‐like activities linked to cytochrome c release through mechanisms that are independent from the MAP kinase systems of p38 and JNK. Elucidating some of the novel neuroprotective pathways employed by EPO may further the development of new therapeutic strategies for neurodegenerative disorders. © 2002 Wiley‐Liss, Inc.
Neurotrophins facilitate neuronal differentiation of cultured neural stem cells via induction of mRNA expression of basic helix‐loop‐helix transcription factors Mash1 and Math1
Authors: Ito Hisanori , Nakajima Aki , Nomoto Hiroshi , Furukawa Shoei 
Published: February 2003

AbstractNeurogenesis is promoted by basic helix‐loop‐helix (bHLH) transcription factors Mash1, Math1, or NeuroD but suppressed by another set, Hes1 and Hes5. It remains unknown what kinds of extracellular signals are involved in their regulation; therefore, the effects of neurotrophins on the expression of bHLH factors and neuronal differentiation were investigated by the use of cultured mouse neural stem cells. Each neurotrophin increased Mash1 and Math1 mRNAs of the stem cells growing in the presence of fibroblast growth factor‐2 (FGF‐2), but did not alter Hes1, Hes5, or NeuroD mRNA levels. Simultaneously, most of the cells expressed nestin but not microtubule‐associated protein 2 (MAP2), and remained undifferentiated. FGF‐2 removal from the medium reduced the levels of Hes1 and Hes5 mRNAs and increased those of Mash1, Math1, and NeuroD mRNAs, resulting in substantial neuronal differentiation. When the cells were pretreated with brain‐derived neurotrophic factor, a neurotrophin, FGF‐2 removal enhanced earlier NeuroD expression and generated many more MAP2‐positive cells. The high level of Mash1 and Math1 that had been elevated at FGF‐2 withdrawal accelerated NeuroD expression in cooperation with the reduced Hes1 and Hes5 expression. Our present results suggest that neurotrophins stimulate neuronal differentiation by altering the balance of expression of various bHLH transcription factors. © 2002 Wiley‐Liss, Inc.