bluuebunny/crossref_metadata_2025_split huggingface dataset:
A case study of surrogate species in aquatic conservation planning
Authors: Hitt Nathaniel P. , Frissell Christopher A. 
Published: November 2004

Abstract
The use of surrogate species (i.e. keystones, indicators, umbrellas) has been advocated for the conservation of target taxa and communities.
A recent Habitat Conservation Plan, which provided conservation measures intended to protect multiple aquatic species of concern over a large area, established an important precedent for surrogate species in aquatic conservation pursuant to the US Endangered Species Act.
The Habitat Conservation Plan's application of federally threatened bull trout was evaluated as an umbrella species for westslope cutthroat trout, which is in decline but not listed under the Act. Approximately 75% of known westslope cutthroat trout strongholds are not captured within bull trout strongholds west of the continental divide. The Habitat Conservation Plan failed to evaluate the suitability of this umbrella species and consequently failed to cover important priority areas for westslope cutthroat trout conservation.
This case study highlights the feasibility and importance of formally validating assumptions of surrogate species utility in multi‐species conservation planning.
Copyright © 2004 John Wiley & Sons, Ltd.
BINAP/1,4‐Diamine—Ruthenium(II) Complexes for Efficient Asymmetric Hydrogenation of 1‐Tetralones and Analogues.
Authors: Ohkuma Takeshi , Hattori Tomonori , Ooka Hirohito , Inoue Tsutomu , Noyori Ryoji 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Microwave‐Enhanced Reduction of Nitro and Azido Arenes to N‐Arylformamides Employing Zn—HCOONH4: Synthesis of 4(3H)‐Quinazolinones and Pyrrolo[2,1‐c][1,4]benzodiazepines.
Authors: Kamal Ahmed , Reddy K. Srinivasa , Prasad B. Rajendra , Babu A. Hari , Ramana A. Venkata 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Deoxyfluorination of Alcohols Using N,N‐Diethyl‐α,α‐difluoro‐(m‐methylbenzyl)amine.
Authors: Kobayashi Shingo , Yoneda Atushi , Fukuhara Tsuyoshi , Hara Shoji 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Highly Stereoselective Approach to Alk‐2‐yne‐1,4‐diols by Oxazaborolidine‐Mediated Reduction of Alk‐2‐yne‐1,4‐diones.
Authors: Ariza Xavier , Bach Jordi , Berenguer Ramon , Farras Jaume , Fontes Montserrat , Garcia Jordi , Lopez Marta , Ortiz Jordi 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Asymmetric Lithium(I) and Copper(II) Alkoxy‐N‐heterocyclic Carbene Complexes; Crystallographic Characterization and Lewis Acid Catalysis.
Authors: Arnold Polly L. , Rodden Mark , Davis Kate M. , Scarisbrick Andrew C. , Blake Alexander J. , Wilson Claire 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
First Planar Chiral Bidentate Ligand Based on a (η5‐Cyclopentadienyl)(η4‐cyclobutadiene) Cobalt Backbone: High Efficiency in Enantioselective Palladium‐Catalyzed Allylic Substitutions.
Authors: Gomez Arrayas Ramon , Garcia Mancheno Olga , Carretero Juan C. 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Asymmetric Synthesis of trans‐3‐Amino‐4‐alkylazetidin‐2‐ones from Chiral N,N‐Dialkylhydrazones.
Authors: Diez Elena , Fernandez Rosario , Marques‐Lopez Eugenia , Martin‐Zamora Eloisa , Lassaletta Jose M. 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Preparative Synthesis of 7‐Carboxy‐2‐R‐isoindol‐1‐ones.
Authors: Varlamov A. V. , Boltukhina E. V. , Zubkov F. I. , Sidorenko N. V. , Chernyshev A. I. , Grudinin D. G. 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Investigations in the Area of Amines and Ammonium Compounds. Part 237. Synthesis of 2,2‐Dialkyl‐4‐hydroxymethylbenzo[f]isoindolinium and 2,2‐Dialkyl‐4‐hydroxymethylisoindolinium Salts.
Authors: Chukhadzhyan E. O. , Gevorkyan. A. R. Gevorkyan. A. R. , Chukhadzhyan El. O. , Shakhatuni K. G. , Kinoyan F. S. , Panosyan G. A. 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Competitive Photochemical Pathways in the Rearrangement of Tetrasubstituted 4H‐Thiopyrans.
Authors: Pirelahi Hooshang , Atarodiekashani Assieh , Seyyedmoossavi Seyyedmajid , Daryanavardedargahani Hossein 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Diels—Alder Cycloaddition of 2‐Azadienes to Methyl 2‐(2,6‐Dichlorophenyl)‐2H‐azirine‐3‐carboxylate in the Synthesis of Methyl 4‐Oxo‐1,3‐diazabicyclo[4.1.0]heptane‐6‐carboxylates.
Authors: Alves M. Jose , Duraes M. Miguel , Fortes A. Gil 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Synthesis of 1,6‐Polymethylene Pyrimidines Based on 4‐(1‐Azacycloalkylidine)‐1,3‐oxazol‐5‐ones.
Authors: Nazarenko K. G. , Shvidenko K. V. , Tolmachev A. A. 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
An Efficient and Facile One‐Pot Synthesis of Structurally Unique 2,4,6‐Tris(arylchalcogeno)‐1,3,5‐triazine and 1,3,5‐Tris(arylchalcogeno)‐2,4,6‐trimethylbenzene.
Authors: Milton Marilyn Daisy , Kumar Naveen , Sokhi Sarbjot Singh , Singh Sarika , Singh Jai Deo 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Substituted 1,2‐Thiazetidine 1,1‐Dioxides. Synthesis of (RS)‐ and (S)‐1,2‐Thiazetidine‐3‐acetic Acid 1,1‐Dioxide and Its Reactions with Amino Acids and Dipeptides.
Authors: Roehrich Till , Thaher Bassam Abu , Manicone Nico , Otto Hans‐Hartwig 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Unprecedented Stereospecific Synthesis of a Novel Tetracyclic Ring System, a Hybrid of Tetrahydropyrrolo[2,3‐b]indole and Tetrahydroimidazo[1,2‐a]indole, via a Domino Reaction upon a Tryptophan‐Derived Amino Nitrile.
Authors: Gonzalez‐Vera Juan A. , Garcia‐Lopez M. Teresa , Herranz Rosario 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Synthesis and Biological Activity of 22‐Oxa CD‐Ring Modified Analogues of 1α,25‐Dihydroxyvitamin D3: Spiro[5.5]undecane CF‐Ring Analogues.
Authors: Schepens Wim , Van Haver Dirk , Vanderwalle Maurits , De Clercq Pierre J. , Bouillon Roger , Verstuyf Annemieke 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Organotin(IV)n+ Complexes Formed with Biologically Active Ligands
Authors: Nagy L. , Szorcsik A. , Schrantz K. , Sletten J. , Kamu E. , Jankovics H. , Jancso A. , Scopelliti M. , Deak A. , Pellerito L. 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Biochemical Engineering of Solid‐State Fermentation
Authors: Weber F. J. , Oostra J. , Nagel F. J. I. , Schutyser M. A. I. , Hoogschagen M. J. , Rahardjo Y. S. P. , Zhu Y. , Boom R. M. , Tramper J. , Rinzema A. 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Olefin Epoxidation with Inorganic Peroxides. Solutions to Four Long‐Standing Controversies on the Mechanism of Oxygen Transfer
Authors: Deubel Dirk V. , Frenking Gernot , Gisdakis Philip , Herrmann Wolfgang A. , Roesch Notker , Sundermeyer Joerg 
Published: November 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
One‐Pot Synthesis of Pyridyltellurium Derivatives from a Reaction with Isopropylmagnesium Chloride and X‐ray Crystal Structures of Various Pyridyl Ditellurides
Authors: Bhasin Kuldip K. , Arora Veena , Klapötke Thomas M. , Crawford Margaret‐Jane 
Published: November 2004

AbstractA one‐pot synthesis of various symmetrical and unsymmetrical 2‐pyridyl‐, 2‐bromo‐5‐pyridyl‐, and 2,5‐dibromo‐3‐pyridyltellurium compounds has been carried out, at room temperature, by selective single bromine‐magnesium exchange of 2‐bromo‐, 2,5‐dibromo‐ and 2,3,5‐tribromopyridine, respectively, with isopropylmagnesium chloride. This exchange reaction gives the corresponding pyridylmagnesium chlorides, which, upon insertion of elemental tellurium (activated), give the pyridyltelluromagnesium chlorides, and, subsequently, the corresponding dipyridyl ditellurides upon aerial oxidation. The pyridyltelluromagnesium chlorides give unsymmetrical pyridyltellurium derivatives in good yield upon treatment with alkyl halides. The X‐ray crystal structures of bis(2‐pyridyl) ditelluride, bis(2,5‐dibromo‐6‐methyl‐3‐pyridyl) ditelluride and bis(2,5‐dibromo‐3‐pyridyl) ditelluride are discussed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
The Anderson‐Type Anion (TeMo6O24)6− − A Multidentate Ligand for Trivalent Rare Earth Cations
Authors: Drewes Daniel , Limanski Eva Melanie , Krebs Bernt 
Published: November 2004

AbstractThe syntheses and structural characterizations of four novel lanthanide polyoxomolybdates containing the Anderson‐type anion (TeMo6O24)6− are presented. Depending on the size of the trivalent rare earth cations, in the solid‐state structures of {[La(H2O)6]2(TeMo6O24)}n·6nH2O (1), {[Ce(H2O)7]2(TeMo6O24)}n·7nH2O (2), {[Pr(H2O)7]2(TeMo6O24)}n·8nH2O (3) and {[Nd(H2O)7]2(TeMo6O24)}n·8nH2O (4) two different arrangements of the building unit are present. The (TeMo6O24)6− anion acts as a hexadentate ligand for LaIII and as a tetradentate ligand for CeIII, PrIII and NdIII, leading to two different infinite one‐dimensional chains. The crystal structures of the new compounds are compared with known lanthanide polyoxomolybdates containing the (TeMo6O24)6− anion and the influence of the LnIII ionic radii is discussed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis of 1,3,5,2λ5‐Triazaphosphinines by Intramolecular Cyclisation of (N‐Cyanophosphorimidoyl)guanidines and Diguanidinophosphonium Chlorides
Authors: Inguimbert Nicolas , Jäger Lothar , Taillefer Marc , Biedermann Matthias , Cristau Henri‐Jean 
Published: November 2004

AbstractThe sodium phosphonium diylide Na[Ph2P(NCN)2] (3) − the first example of a stabilised phosphonium diylide − was synthesised by treatment of sodium diphenylphosphide with 2 equiv. of cyanic azide. Compound 3 reacted with alkyl‐ and arylammonium salts [RR′NH2]Cl {R = PhCH2, tBu, Ph; R′ = H; RR′ = −[(CH2)2O(CH2)2]−}. Depending on the molar ratios (1:1 or 1:2), (N‐cyano‐P,P‐diphenylphosphorimidoyl)guanidines Ph2P(NCN)N=C(NH2)NRR′ (8) or diguanidinodiphenylphosphonium chlorides [Ph2P{N=C(NH2)NRR′}2]Cl (10) were formed. When molten, compounds 8 yielded new cyclic 1,3,5,2λ5‐triazaphosphinines 11. The fusion of compound 10 allowed the formation of the same 1,3,5,2λ5‐triazaphosphinines 11, along with the formation of NH4Cl or [PhNH3]Cl. A crystal structure analysis of 4‐amino‐6‐morpholino‐2,2‐diphenyl‐1,3,5,2λ5‐triazaphosphinine (11a) revealed an almost planar six‐membered ring for the 1,3,5,2λ5‐triazaphosphinine template. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis of Thioglycosides by Tetrathiomolybdate‐Mediated Michael Additions of Masked Thiolates
Authors: Sridhar Perali Ramu , Prabhu Kandikere Ramaiah , Chandrasekaran Srinivasan 
Published: November 2004

AbstractAn efficient one‐pot methodology for the synthesis of thioglycosides in excellent yields under neutral conditions through the use of benzyltriethylammonium tetrathiomolybdate [(BnNEt3)2MoS4; 1] as a sulfur‐transfer reagent has been developed. The reagent 1 reacts with sugar halides to give sugar disulfides, which then undergo reductive cleavage in situ to provide the corresponding thiolates, followed by Michael addition to give the corresponding thioglycosides. Further, the utility of this one‐pot reaction in aqueous medium has been exemplified through the use of ammonium tetrathiomolybdate [(NH4)2 MoS4; 2]. The application of this methodology has been extended to the synthesis of a variety of thiosugar analogues with excellent diastereoselectivity through inter‐ and intramolecular reactions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis and Conformation Analysis of New Perphosphorylated Calix[4]resorcinarenes
Authors: Maslennikova Vera I. , Serkova Olga S. , Gruner Marget , Goutal Sigrid , Bauer Ingmar , Habicher Wolf D. , Lyssenko Konstantin A. , Antipin Mikhail Yu. , Nifantyev Eduard E. 
Published: November 2004

AbstractThe octaphosphorylation of calix[4]resorcinarenes 1 by 2‐dialkylamino‐1,3,2‐diheterophosphorinanes 2 is described, and the effect of different factors on the structures of the resulting perphosphorylated products 3−5 was studied. Conformation analysis of these compounds by correlated 2D NMR spectroscopy and X‐ray diffraction analysis was performed, and it was found that compounds 3−5, like the initial resorcinarenes 1, each have the all‐cis configuration of the R groups in the methylidene bridges of the calixarene system, but different orientations of benzene rings and phosphorinane fragments with respect to one another and to the macrocycle plane. Perphosphorylated resorcinarenes 3a−c, 4a and 5a with R = alkyl exist in flattened cone conformations with the phosphorinane fragments on the same side of the macrocycle plane. The conformations of the perphosphorylated resorcinarenes 3d, 4b and 5b with R = Ph change to forms intermediate between flattened cone and 1,3‐alternate. The phosphorus fragments in these compounds are located on opposite sides of the macrocycle plane. It was shown that the oxidation and sulfurisation of phosphocalixarenes 3 proceed without any change in the spatial organisation of the macrocyclic system. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Reductive and Oxidative Transformations of the N‐(Cyanomethyl)oxazolidine System to Expand the Chiral Pool of Piperidines
Authors: François David , Poupon Erwan , Kunesch Nicole , Husson Henri‐Philippe 
Published: November 2004

AbstractTwo new reactions have been exploited to modify piperidine scaffolds containing the chiral, non‐racemic N‐(cyanomethyl)oxazolidine system. A Raney nickel mediated decyanation was studied first, followed by an oxidative process using potassium permanganate to furnish enantiopure lactams including oxopipecolic acid derivatives. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Novel Asymmetric Wittig Reaction: Synthesis of Chiral Allenic Esters
Authors: Pinho e Melo Teresa M. V. D. , Cardoso Ana L. , d’A. Rocha Gonsalves António M. , Costa Pessoa João , Paixão José A. , Beja Ana M. 
Published: November 2004

AbstractWittig reactions between 10‐(phenylsulfonyl)isobornyl (triphenylphosphoranylidene)acetates (1 and 6) and ketenes resulted in asymmetric induction, with the selective synthesis of allenes with axial chirality. Use of the (1R)‐(−)‐10‐(phenylsulfonyl)isoborneol unit allows the synthesis of allenes with S configuration, whereas use of the (1S)‐(+)‐10‐(phenylsulfonyl)isoborneol unit produces allenes with R configuration. The structure of (1R)‐(−)‐10‐(phenylsulfonyl)isobornyl (S)‐5,5‐dimethylhexa‐2,3‐dienoate (2e) was determined by X‐ray crystallography. Chirooptical studies of the allenic esters were carried out, confirming that two sets of enantiomeric derivatives were obtained. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Pyrano[2,3‐b]dioxanes through Bisacetalic Annulation of 2‐Ketosugars to Glycol
Authors: Cuny Eckehard , Lichtenthaler Frieder W. , Lindner Hans J. 
Published: November 2004

AbstractThe utility of 2‐ketohexosyl (“ulosyl”) bromides has been extended to the straightforward generation of cis‐fused pyrano[2,3‐b]dioxanes (1,4,5‐trioxadecalins) of type 11 and 13 by β‐specific and α‐selective glycosidation with glycol, and subsequent intramolecular hemiketalization. Mild basic conditions elicit highly stereoselective rearrangements to trioxadecalinones 22−25, representing the structurally and configurationally correct framework of steroidal natural products in which the sugar portion is doubly glycosidically linked to the aglycon. Exposure of 11 or 13 to mineral acid results in an essentially stereospecific contraction of the pyranoid ring to yield trioxaspiro[4,5]decanes. Mechanistic considerations of the unusual rearrangements observed are discussed in light of available experimental facts and the scarce existing analogies. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
2‐Alkyl‐1,2,3,4‐benzotetrazinium Tetrafluoroborates: Their Reaction with Nucleophiles
Authors: Lipilin Dmitry L. , Smirnov Oleg Y. , Churakov Aleksandr M. , Strelenko Yuri A. , Tyurin Aleksei Y. , Ioffe Sema L. , Tartakovsky Vladimir A. 
Published: November 2004

AbstractTreatment of 2‐alkyl‐1,2,3,4‐benzotetrazinium tetrafluoroborates with a nucleophile (AlkO−, ArO−, AcO−, Hal−, CN−, NCO−, ArNH2, AlkNH2, Alk2NH), at room temperature, results in elimination of an N2 molecule to afford ortho‐substituted azobenzenes. This reaction could be suitable for mild phenylation of carboxylic acids and other compounds containing active hydrogen. A plausible reaction pathway for the reaction is discussed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Bias correction for histogram estimator using line transect sampling
Authors: Eidous Omar M. 
Published: November 2004

AbstractThis article proposes a simple approach for reducing the bias of the traditional histogram estimator using line transect sampling. The approach uses the bias correction technique, which produces a new estimator for density of objects D. The proposed estimator reduces the bias from O(h2) to O(h3) as h → 0 under the shoulder condition assumption. The asymptotic properties of the proposed estimator are derived under some mild assumptions, and the optimal formula for the bin width is given. Small‐sample properties of the proposed estimator are studied and compared with some other existence estimators by using a simulation technique. The results show that improvements over the traditional histogram estimator often can be realized even at small or moderate sample size. Copyright © 2004 John Wiley & Sons, Ltd.
Humoral and contact interactions in astroglia/stem cell co‐cultures in the course of glia‐induced neurogenesis
Authors: Környei Zsuzsanna , Szlávik Vanda , Szabó Bálint , Gócza Elen , Czirók András , Madarász Emília 
Published: November 2004

AbstractAstroglial cells support or restrict the migration and differentiation of neural stem cells depending on the developmental stage of the progenitors and the physiological state of the astrocytes. In the present study, we show that astroglial cells instruct noncommitted, immortalized neuroectodermal stem cells to adopt a neuronal fate, while they fail to induce neuronal differentiation of embryonic stem cells under similar culture conditions. Astrocytes induce neuron formation by neuroectodermal progenitors both through direct cell‐to‐cell contacts and via short‐range acting humoral factors. Neuron formation takes place inside compact stem cell assemblies formed 30– 60 h after the onset of glial induction. Statistical analyses of time‐lapse microscopic recordings show that direct contacts with astrocytes hinder the migration of neuroectodermal progenitors, while astroglia‐derived humoral factors increase their motility. In non‐contact co‐cultures with astrocytes, altered adhesiveness prevents the separation of frequently colliding neural stem cells. By contrast, in contact co‐cultures with astrocytes, the restricted migration on glial surfaces keeps the cell progenies together, resulting in the formation of clonally proliferating stem cell aggregates. The data indicate that in vitro maintained parenchymal astrocytes (1) secrete factors, which initiate neuronal differentiation of neuroectodermal stem cells; and (2) provide a cellular microenvironment where stem cell/stem cell interactions can develop and the sorting out of the future neurons can proceed. In contrast to noncommitted progenitors, postmitotic neuronal precursors leave the stem cell clusters, indicating that astroglial cells selectively support the migration of maturing neurons as well as the elongation of neurites. © 2004 Wiley‐Liss, Inc.
Lipopolysaccharide affects Golli expression and promotes proliferation of oligodendrocyte progenitors
Authors: Filipovic Radmila , Zecevic Nada 
Published: November 2004

AbstractProliferation of oligodendrocyte progenitor cells (OPCs) is important for initial myelination as well as for remyelination in demyelinating diseases. Previously, we showed that numerous OPCs and activated microglia, are present around multiple sclerosis lesions, and that they accumulate Golli proteins. Golli proteins, present in both neuronal and immune cells, might have a role in the immune processes, as well as in development of neurons and oligodendrocytes. We hypothesize that Golli proteins, generated by microglia in response to inflammation, promote proliferation of OPCs. To test this hypothesis, we induced inflammation in neonatal mouse brain slice culture with bacterial endotoxin lipopolysaccharide (LPS). Treated slices showed an increase in the number of OPCs. Several results support the notion that this effect of LPS is conveyed through activation of microglia and upregulation of Golli proteins. First, LPS‐treated brain slices have increased expression of Golli proteins observed by immunofluorescence and Western blot analysis. Second, Golli proteins were demonstrated only in the conditioned medium from LPS‐treated microglial cell cultures (LPS‐MCM), and were absent in either the conditioned media from LPS‐treated astrocytes or the control media. Third, proliferation of purified OPCs was promoted with LPS‐MCM or Golli proteins, but not with LPS alone. Taken together, these results demonstrate that microglia and/or microglia secreted factors, are necessary for the LPS‐promoted proliferation of OPCs and suggest possible involvement of Golli proteins as one of mediators in this process. © 2004 Wiley‐Liss, Inc.
In vivo efficacy of HSV‐TK transcriptionally targeted to the tumour vasculature is augmented by combination with cytotoxic chemotherapy
Authors: Mavria Georgia , Harrington Kevin J. , Marshall Christopher J. , Porter Colin D. 
Published: November 2004

AbstractBackgroundRetroviral vectors are suitable for targeting endothelial cells in the tumour neovasculature because of their intrinsic selectivity for proliferating cells. Previously, we inserted regulatory elements of the endothelial‐specific prepro‐endothelin‐1 (ppET1) promoter in retroviral vectors to generate high‐titre, replication‐defective recombinant retroviruses that restricted gene expression to the vascular compartment of tumours.MethodsA retroviral vector was generated in which expression of herpes simplex virus thymidine kinase (HSV‐TK) was transcriptionally restricted to endothelial cells, under the control of a hybrid ppET‐1 LTR. Xenograft tumour models were used to determine the efficacy of targeting HSV‐TK to the tumour vasculature. Subsequently, vascular‐targeted gene therapy was combined with chemotherapeutic agents.ResultsBreast or colorectal xenograft tumour growth was reduced and survival was increased in response to ganciclovir treatment. Treatment resulted in widespread vascular disruption and tumour cell apoptosis. In colorectal tumours, combination with irinotecan, a cytotoxic drug used to treat colorectal cancer, significantly increased survival compared to drug alone. No beneficial effect on survival was observed when combined with cisplatin, a cytotoxic drug not in clinical use for this tumour type. On the basis of their relative efficacies in vitro against tumour and endothelial cells, co‐operativity with irinotecan likely derives from additionally targeting the peripheral tumour cells that survive the anti‐vascular treatment.ConclusionsWe show that the ppET1‐targeted vector is efficacious for therapeutic gene expression in vivo, validating a strategy targeted to tumour vasculature, and demonstrate that vascular targeting combined with appropriate chemotherapy is more effective than either therapy alone. Copyright © 2004 John Wiley & Sons, Ltd.