bluuebunny/crossref_metadata_2025 huggingface dataset:
An Efficient Synthesis of 4H,5H‐Pyrano[3,4‐c]pyran‐4,5‐diones from a Suitably Functionalized 2H‐Pyran‐2‐one.
Authors: Sil Diptesh , Ram Vishnu Ji
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Structure—Reactivity Relationships in Oxidative Carbon—Carbon Bond Forming Reactions: A Mild and Efficient Approach to Stereoselective Syntheses of 2,6‐Disubstituted Tetrahydropyrones.
Authors: Wang Lijun , Seiders John R. II , Floreancig Paul E.
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
A 2:1 Coupling Reaction of Arynes with Aldehydes via o‐Quinone Methides: Straightforward Synthesis of 9‐Arylxanthenes.
Authors: Yoshida Hiroto , Watanabe Masahiko , Fukushima Hiroyuki , Ohshita Joji , Kunai Atsutaka
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Concise Synthesis of trans‐ and cis‐3,4‐Disubstituted Piperidines Based on Regio‐ and Stereoselective Allylation of Cyclopentenyl Esters.
Authors: Igarashi Junji , Ishiwata Hiroyuki , Kobayashi Yuichi
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Synthesis of Chiral Nonracemic 1‐(2‐Pyridinyl)ethylamines: Stereospecific Introduction of Amino Function onto the 2‐Pyridinylmethyl Carbon Center.
Authors: Uenishi Jun'ichi , Hamada Masahiro , Aburatani Sachiko , Matsui Katsuya , Yonemitsu Osamu , Tsukube Hiroshi
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Search for Histamine H3 Receptor Ligands with Combined Inhibitory Potency at Histamine N‐Methyltransferase: ω‐Piperidinoalkanamine Derivatives.
Authors: Grassmann Sven , Apelt Joachim , Ligneau Xavier , Pertz Heinz H. , Arrang Jean‐Michel , Ganellin C. Robin , Schwartz Jean‐Charles , Schunack Walter , Stark Holger
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Stereodirected Catalytic Synthesis of Perhydroacridines and Their Isologs from Decahydroacridine‐1,8‐diones.
Authors: Nikolaeva T. G. , Shchekotikhin Yu. M.
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Improved Synthesis of 7‐(Alkyl/aralkyl)guanines.
Authors: Vidal A. , Madelmont J.‐C.
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
1,3‐Dipolar Cycloaddition Reactions with 1,2,3‐Triazinium Ylides.
Authors: Maettner Michael , Neunhoeffer Hans
Published: January 2005

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Efficient Synthesis of Acylsilanes Using Morpholine Amides.
Authors: Clark Christopher T. , Milgram Benjamin C. , Scheidt Karl A.
Published: January 2005

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Application of Directed Orthometalation Toward the Synthesis of Aryl Siloxanes.
Authors: Seganish W. Michael , DeShong Philip
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Ru3(CO)12‐Catalyzed Silylation of Benzylic C—H Bonds in Arylpyridines and Arylpyrazoles with Hydrosilanes via C—H Bond Cleavage.
Authors: Kakiuchi Fumitoshi , Tsuchiya Kazuyuki , Matsumoto Mitsutaka , Mizushima Eiichiro , Chatani Naoto
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Nucleophilic Transformation of Cyclic Phosphate Triesters.
Authors: Ashkenazi Nissan , Karton Yishai , Segall Yoffi
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Double Phosphinylation of Propargylic Alcohols: A Novel Synthetic Route to 1,2‐Bis(diphenylphosphino)ethane Derivatives.
Authors: Milton Marilyn Daisy , Onodera Gen , Nishibayashi Yoshiaki , Uemura Sakae
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Asymmetric Synthesis and Translational Competence of L‐α‐(1‐Cyclobutenyl)glycine.
Authors: Jayathilaka Lasanthi P. , Deb Mahua , Standaert Robert F.
Published: January 2005

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A Novel Stereospecific Synthesis of Glycosyl Cyanides from 1,2‐O‐Sulfinyl Derivatives.
Authors: Benksim Abdelhafid , Beaupere Daniel , Wadouachi Anne
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Stereoselective Synthesis of Azasugars by Electrochemical Oxidation.
Authors: Furukubo Shigeru , Moriyama Noriaki , Onomura Osamu , Matsumura Yoshihiro
Published: January 2005

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New C(4)‐Functionalized Colchicine Derivatives by a Versatile Multicomponent Electrophilic Aromatic Substitution.
Authors: Bensel Nicolas , Lagnoux David , Niggli Verena , Wartmann Markus , Reymond Jean‐Louis
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
1‐Methylgalanthamine Derivatives.
Authors: Hemetsberger Margit , Treu Matthias , Jordis Ulrich , Mereiter Kurt , Hametner Christian , Froehlich Johannes
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Modified Tricyclic Analogues of Acyclovir. A Direct Alkynylation in the Fused Ring.
Authors: Zeidler Joanna
Published: January 2005

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Binding Features of BCL2‐Targeted Oligodeoxynucleotides with K562 Cells
Authors: Timofeev A. M. , Borovkova T. V. , Akhlynina T. V. , Nydenova N. M. , Grineva N. I.
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Toward the Development of Metal‐Free Synthetic Nucleases: Cleavage of a Model Substrate by 1,4‐Diazabicyclo[2.2.2]octane Derivatives.
Authors: Koroleva Lyudmila S. , Silnikov Vladimir N.
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Binding Properties of the Conjugates of Oligo(2′‐O‐Methylribonucleotides) with Minor Groove Binders Targeted to Double Stranded DNA
Authors: Novopashina D. S. , Sinyakov A. N. , Ryabinin V. A. , Venyaminova A. G. , Perrouault L. , Brunet E. , Giovannangeli C. , Boutorine A. S.
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Two‐Component 10—23 DNA Enzymes
Authors: Fokina A. A. , Kuznetsova M. A. , Repkova M. N. , Venyaminova A. G.
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Efficient Cleavage of DS DNA by Bleomycin Conjugated via Hexaethylene Glycol Linker to Triplex‐Forming Oligonucleotides
Authors: Vorobjev Pavel , Tchaika Olessia , Zarytova Valentina
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Comparison of Enzymatic Properties of DNA‐Abzymes and Human DNAses
Authors: Baranovskii A. G. , Odintsova E. S. , Buneva V. N. , Doronin B. M. , Nevinsky G. A.
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Phytochemical Investigation of Shilajit
Authors: Ali M. , Sahrawat I. , Singh O.
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Chemistry and Biology of Diazonamide A: Second Total Synthesis and Biological Investigations.
Authors: Nicolaou K. C. , et al. et al.
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Switching of Molecular Spin States in Inorganic Complexes by Temperature, Pressure, Magnetic Field and Light: Towards Molecular Devices
Authors: Bousseksou Azzedine , Molnar Gabor , Matouzenko Galina
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Nucleophilic Catalysis via Phosphine Conjugate Addition: Vinyl Sulfones as Reacting Partners in Catalytic Cross‐Michael Cycloisomerization
Authors: Luis Ana Liza , Krische Michael J.
Published: January 2005

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Symmetry Breaking: An Epistemological Note
Authors: Avalos Martin , Babiano Reyes , Cintas Pedro , Jimenez Jose L. , Palacios Juan C.
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Phosphines: Chemical All‐rounder?
Authors: Oestreich M.
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Experimental Data Checker: Better Information for Organic Chemists
Authors: Adams S. E. , Goodman J. M. , Kidd R. J. , McNaught A. D. , Murray‐Rust P. , Norton F. R. , Townsend J. A. , Waudby C. A.
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
A Dash of Proline Makes Things Sweet
Authors: Sorensen Erik J. , Sammis Glenn M.
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Pentaerythritol and Its Congeners: Versatile Building Blocks for the Construction of Oligomeric Bioconjugates and Small Molecule Libraries on a Solid Support
Authors: Katajisto Johanna , Heinonen Petri , Loennberg Harri
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Japan Bats a Triple
Authors: West Robert
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
4‐Thiazolidones: Centenarian History, Current Status and Perspectives for Modern Organic and Medicinal Chemistry
Authors: Lesyk R. B. , Zimenkovsky B. S.
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Thienothiophenes: Synthesis and Applications
Authors: Comel A. , Sommen G. , Kirsch G.
Published: January 2005

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Transient Phenoxyl Radicals: Formation and Properties in Aqueous Solutions
Authors: Steenken S. , Neta P.
Published: January 2005

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Chemical Synthesis of All Naturally Occurring Phosphorylated Inositol Phospholipids
Authors: Bruzik Karol S.
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Synthesis of Propylene Oxide in CO2 as Solvent
Authors: Schilling Gerhard
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Synthesis, Structure, and Biological Activity of Acylpyruvic Acids and Related 2‐Imino Derivatives
Authors: Koz'minykh V. O. , Koz'minykh E. N.
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Towards Liquid Crystal Synthesis Using High Throughput and Micro Reactor Technologies
Authors: Styring Peter
Published: January 2005

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Approaches to the Preparation of Sphinganines
Authors: Howell Amy R. , So Regina C. , Richardson Stewart K.
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Tetrathiafulvalenes, Oligoacenenes, and Their Buckminsterfullerene Derivatives: The Brick and Mortar of Organic Electronics
Authors: Bendikov Michael , Wudl Fred , Perepichka Dmitrii F.
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
High Magnetic Fields: A Tool for Studying Electronic Properties of Layered Organic Metals
Authors: Kartsovnik Mark V.
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
103Rh NMR Spectroscopy and Its Application to Rhodium Chemistry
Authors: Ernsting Jan Meine , Gaemers Sander , Elsevier Cornelis J.
Published: January 2005

For Abstract see ChemInform Abstract in Full Text.
Alkylation of 5‐ and 6‐Methylindolo[2,3‐b]quinoxalines: Revised Structures of the N,N′‐Dimethylated Salts
Authors: Helissey Philippe , Desbène‐Finck Stéphanie , Giorgi‐Renault Sylviane
Published: January 2005

N,N′‐Dialkylation of indolo[2,3‐b]quinoxaline could theoretically furnish three isomers, that is, salts dialkylated at the 5,6‐, the 6,11‐, and the 5,11‐positions. By using the 2,3‐dimethylated derivatives as models, the regioisomeric salts were selectively synthesized either by alkylation of the tetracycle or by cyclization of 1‐methylisatin with N,4,5‐trimethylbenzene‐1,2‐diamine. The structure of the N,N′‐dimethyl salts were unambiguously determined by NMR correlation sequences (1H‐1H NOESY, 1H‐13C HMQC, and 1H‐13C HMBC). The results of these studies show that the previous findings from the dialkylation of indoloquinoxaline need revision. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Formation and Structure of Conjugated Salen‐Cross‐Linked Polymers and Their Application in Asymmetric Heterogeneous Catalysis
Authors: Nielsen Morten , Thomsen Anne H. , Jensen Torben R. , Jakobsen Hans J. , Skibsted Jørgen , Gothelf Kurt V.
Published: January 2005

A new type of cross‐linked condensation polymer was obtained by the reaction of 1,3,5‐tris[(5‐tert‐butyl‐3‐formyl‐4‐hydroxyphenyl)ethynyl]benzene (1) with ethylenediamine. Solid‐state 13C{1H} CP/MAS NMR analysis showed that the polymer was pure and highly cross‐linked and powder synchrotron X‐ray diffraction indicated some degree of local structural order in the polymer. A chiral manganese−salen‐bridged polymer was obtained by the condensation of 1 with (1R,2R)‐1,2‐diphenyl‐1,2‐diaminoethane (3a) or (1R,2R)‐1,2‐diaminocyclohexane (3b) in the presence of Mn(OAc)2. These rigid chiral metal−salen polymers can catalyze the epoxidation of cis‐2‐methylstyrene with high conversion, diastereoselectivity and enantioselectivities of up to 67% ee. The polymeric catalyst can be reused several times without reduced activity or selectivity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Enantiopure and Racemic Chiral Nitronyl Nitroxide Free Radicals: Synthesis and Characterization
Authors: Hirel Catherine , Pécaut Jacques , Choua Sylvie , Turek Philippe , Amabilino David B. , Veciana Jaume , Rey Paul
Published: January 2005

A synthetic route to a series of homochiral (and achiral) nitronyl nitroxides derived from rac‐(and meso)‐3,4‐dimethyl‐3,4‐dinitrohexane is described. The two forms of this precursor, meso and rac, were identified unambiguously and reduced to the corresponding meso‐ and rac‐diamines. The rac‐diamine was condensed with an enantiopure aldehyde specifically designed to give a diastereomeric mixture of imidazolidines easily separated by flash chromatography. Both enantiopure diamines were then obtained by acidic hydrolysis of these imidazolidines. The absolute configurations of the diamino precursors were determined by X‐ray crystallography of single crystals of a manganese(II) complex [(R,R,R)‐5E·Mn(hfac)2] of a nitroxide containing a third chiral center of known configuration. A series of homochiral nitronyl nitroxides was then prepared from the enantiopure diamino precursors by condensation with aldehydes, followed by oxidation. Their structural properties were compared to those of their achiral meso counterparts and it was found that the puckering of the five‐membered ring is dependent on the chirality of the imidazolyl unit. The radicals show marked optical activity, as explored by polarimetry and circular dichroism spectroscopy. These paramagnetic building blocks of known absolute configuration include chiral centers adjacent to the oxyl groups, and since they exhibit C2 symmetry they are well suited for coordination chemistry studies because stereochemical complexity is minimized. They have been specifically designed for further developments of the metal‐radical approach to molecular magnetic materials. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Palladium‐Catalyzed Arylation of Linear and Cyclic Polyamines
Authors: Beletskaya Irina P. , Bessmertnykh Alla G. , Averin Alexei D. , Denat Franck , Guilard Roger
Published: January 2005

The palladium‐catalyzed arylation of polyamines is investigated and it is shown that the C−N coupling reaction for a given substrate is strongly dependent on the nature and the concentration of the catalytic system, as well as the nature of the base employed. The arylation of the primary amino group is favored when both primary and secondary amines are present; selective arylation is then possible without using any protecting group. The reaction of dihalobenzenes with polyamines gives the monoamination products in good yields without any significant formation of diamino compounds or reduced derivatives, unlike what is observed when monoamines are used. The extent of polyarylation of polyamines as a function of the excess of aryl halide and the nature and the amount of catalyst is also studied. Finally, N‐arylation of a macrocyclic tetraamine (cyclam) is performed by using an appropriate catalytic system. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
End‐Capped, Conjugated (Dimethylamino)naphthyl Nanostructures with Alternating (1‐Naphthylethynyl‐p‐phenylethynyl)x Branches on a 1,3,5‐Substituted Benzene Core
Authors: Rodríguez J. Gonzalo , Tejedor J. Luis
Published: January 2005

Alternating (1‐naphthylethynyl‐p‐phenylethynyl)x 1,3,5‐trisubstituted benzene dendrons were efficiently synthesised by the heterocoupling reaction between (1‐naphthylethynyl‐p‐phenyl)xacetylene (x = 1) and 1,3,5‐triiodobenzene in the presence of a palladium‐copper catalyst system. A longer terminal acetylene chain (x = 2) was obtained from the heterocoupling between 1,3,5‐tri(1‐ethynyl‐5‐naphthylethynyl)benzene and the appropriate iodoaryl derivative. The alternating chains, and their dendron structures, show fluorescence emission, with similar wavelengths and quantum yields. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Reinvestigation of the Mechanism of gem‐Diacylation: Chemoselective Conversion of Aldehydes to Various gem‐Diacylates and Their Cleavage under Acidic and Basic Conditions
Authors: Kavala Veerababurao , Patel Bhisma K.
Published: January 2005

The mechanism of gem‐diacylate formation has been studied extensively using tetrabutylammonium tribromide (TBATB) as the catalyst. The reaction proceeds by a nucleophilic attack of an anhydride on an aldehydic carbonyl group, nucleophilic attack of the hemiacylate intermediate on a second molecule of the anhydride, followed by an intermolecular attack of a second acetate group to regenerate the anhydride. gem‐Diacylates of various aliphatic and aromatic aldehydes were obtained directly from the reaction of a variety of aliphatic and aromatic acid anhydrides in the presence of a catalytic quantity of tetrabutylammonium tribromide (TBATB) under solvent‐free conditions. A significant electronic effect was observed during its formation as well as deprotection to the corresponding aldehyde. Chemoselective gem‐diacylation of the aromatic aldehyde containing an electron‐donating group has been achieved in the presence of an aldehyde containing an electron‐withdrawing group. Deprotection of the gem‐diacylate to the parent carbonyl compound can be accomplished in methanol in presence of the same catalyst. Here again, chemoselective deprotection of the gem‐diacylate of a substrate containing an electrondonating group has been achieved in the presence of a substrate containing an electron‐withdrawing group. Both the acid and base stability order of the various gem‐diacylates examined follow a similar order. The stability order determined from the present study is: gem‐dibenzoate > gemdipivalate > gem‐diisobutyrate > gem‐diacetate > gem‐dipropionate. All the gem‐diacylals are more stable under basic conditions than acidic condition. No correlation was found between the stability order and the pKa’s of the corresponding acids; rather, the stability order is directly related to the steric crowding around the carbonyl carbon. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
A Remarkably Efficient Markovnikov Hydrochlorination of Olefins and Transformation of Nitriles into Imidates by Use of AcCl and an Alcohol
Authors: Yadav Veejendra K. , Babu K. Ganesh
Published: January 2005

HCl generated by mixing AcCl with EtOH brings about Markovnikov hydrochlorination of olefins in excellent yields. The products are isolated in states of high purity simply by removal of the volatile components under reduced pressure. Further, nitriles are transformed into imidate hydrochlorides on similar treatment with AcCl and an alcohol. This procedure for nitrile‐imidate transformation is much more efficient than that used previously, which involved continuous passing of HCl gas into the solution of a nitrile in a solvent such as Et2O or benzene and an alcohol until one equivalent had been absorbed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
An Efficient Synthesis of Novel α‐Aminophosphonates Based on a Mannich‐Type Reaction
Authors: Risch Nikolaus , Piper Stefan , Winter Andreas , Lefarth‐Risse Annette
Published: January 2005

Phosphonate‐substituted iminium salt2was used in Mannich reactions with various nucleophiles to obtain novel α‐aminophosphonates. This straightforward and efficient methodology has a broad scope and provides highly functionalized Mannich bases (4and8). Furthermore, vinylic, aromatic and homoallylic α‐aminophosphonates (5,10and12) were synthesized in good yields. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Fluorinations of α‐Seleno Carboxylic Acid Derivatives with Hypervalent (Difluoroiodo)toluene
Authors: Arrica Maria A. , Wirth Thomas
Published: January 2005

A very efficient synthesis of (difluoroiodo)toluene avoiding the use of elemental chlorine and elemental fluorine is described. We have fluorinated a series of α‐acceptor substituted selenides using (difluoroiodo)toluene. The reactions are usually very clean and under the reaction conditions no further oxidized products are observed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Cover Picture: Palladium‐Catalyzed Arylation of Linear and Cyclic Polyamines (Eur. J. Org. Chem. 2/2005)
Authors: Beletskaya Irina P. , Bessmertnykh Alla G. , Averin Alexei D. , Denat Franck , Guilard Roger
Published: January 2005

The cover picture shows the model structures of four compounds among the hundred of arylated linear and cyclic polyamines prepared by palladium‐catalyzed coupling of mono‐ and dihalogenoarenes with various aliphatic or aromatic polyamines. The reaction is strongly dependent on the nature and the concentration of the catalytic system, as well as the nature of the base. The competitive reaction between primary and secondary amines and the monoamination of dihalobenzenes have also been detailed in the article by R. Guilard et al. on p. 261 ff. In the following article by the same authors on p. 281 ff, the method has been applied to the synthesis of numerous nitrogen‐ and oxygen‐containing macrocycles incorporating anthracene or anthraquinone moieties.
Differential induction and activation of NF‐κB transcription complexes in radiation‐induced chromosomally unstable cell lines
Authors: Snyder Andrew R. , Morgan William F.
Published: January 2005

Radiation‐induced genomic instability is a delayed effect of ionizing radiation that may contribute to radiation carcinogenesis. Prior microarray studies investigating gene expression changes in genomically unstable cell lines isolated after radiation exposure uncovered the differential expression of the NF‐κB p105 mRNA. In this study, the functionality of the NF‐κB pathway was examined to determine its role in regulating gene expression changes after oxidative stress in chromosomally stable and unstable human‐hamster hybrid clones. Basal DNA‐binding activity assays showed no significant differences between the clones; however, further experiments established differences in NF‐κB induction in three chromosomally unstable clones after acute hydrogen peroxide treatment. A second assay was used to confirm this differential activity in the chromosomally unstable clones by studying reporter gene activation after treatment with hydrogen peroxide. Yet an initial upstream analysis of the pathway revealed no significant increase in the level of IκBα inhibitor protein in the unstable clones. Downstream tests analyzing the induction of the antiapoptotic target protein Bcl‐2 found variable induction among the stable and unstable clones. These differences did not translate to a reduction in clonogenic survival after acute exposure to oxidative stress, as the irradiated but chromosomally stable clone displayed the most sensitivity. Due to its role in regulating a diverse set of cellular functions, including responses to oxidative stress, alterations in the NF‐κB pathway in chromosomally unstable clones may regulate the differential physiology of a subset of chromosomally unstable clones and could contribute to the perpetuation of the phenotype. However, a specific role for defective induction and activation of this pathway remains unidentified. Environ. Mol. Mutagen., 2005. © 2005 Wiley‐Liss, Inc.
Screening for large mutations of the NF2 gene
Authors: Kluwe Lan , Nygren Anders O.H. , Errami Abdellatif , Heinrich Bianca , Matthies Cordula , Tatagiba Marcos , Mautner Victor
Published: January 2005

Neurofibromatosis 2 (NF2) is a genetic disorder caused by mutational inactivation of the NF2 gene and is characterized by bilateral vestibular schwannomas, spinal tumors, and other benign tumors of the nervous system. Previously, we found intragenic NF2 mutations in 99 of 188 unrelated NF2 patients by exon‐scanning‐based methods. Tumor analysis of 22 de novo NF2 patients led to the identification of 12 additional constitutive NF2 mutations. The remaining 77 patients were further examined for large alterations using the newly developed gene dosage assay multiplex ligation–dependent probe amplification (MLPA). One deletion of a single exon, seven deletions of multiple exons, seven deletions involving the 3′ or 5′ end of the NF2 gene, four deletions involving the whole NF2 gene, and one duplication of three exons were detected. For 47 of the 77 patients, mRNA of adequate quality could be obtained, enabling transcript analysis, which confirmed eight alterations detected by MLPA. In addition, in one family, the mRNA analysis detected an insertion of two exons of another gene. Thus, deletions, duplications, and insertions affecting the NF2 gene were found in 21 cases, which is 11% of the 188 unrelated NF2 patients studied, 16% of the 132 mutations identified, and 27% of the 77 cases in which no intragenic small mutations were detected by exon scanning. The combination of multiple screening techniques facilitated a mutation‐detection rate of 100% for the 21 inherited cases in this study. © 2005 Wiley‐Liss, Inc.
Statistical behavior of complex cancer karyotypes
Authors: Höglund Mattias , Frigyesi Attila , Säll Torbjörn , Gisselsson David , Mitelman Felix
Published: January 2005

Epithelial tumors commonly show complex and variable karyotypes that obscure the identification of general patterns of the karyotypic evolution. To overcome some of these problems, we previously systematically analyzed the accumulated cytogenetic data from individual tumor types by using various statistical means. In the present study, we compare previous results obtained for nine tumor types and perform several meta‐analyses of data obtained from a number of epithelial tumors, including head and neck, kidney, bladder, breast, colorectal, ovarian, and lung cancer, as well as from malignant melanoma and Wilms tumor, with the specific aim of discovering common patterns of karyotypic evolution. We show that these tumors frequently develop through a hypo‐ or a hyperdiploid pathway and progress by an increasing number of alternative imbalances through at least two karyotypic phases, Phases I and II, and possibly through a third, Phase III. During Phase I, the karyotypes exhibited a power law distribution of both the number of changes per tumor and the frequency distribution at which bands were involved in breaks. At the transition from Phase I to Phase II/III, the observed power law distributions were lost, indicating a transition from an ordered and highly structured process to a disordered and chaotic pattern. The change in karyotypic orderliness at the transition from Phase I to Phase II/III was also shown by a drastic difference in karyotypic entropy. © 2005 Wiley‐Liss, Inc.
Centromeric breakage and highly rearranged chromosome derivatives associated with mutations of TP53 are common in therapy‐related MDS and AML after therapy with alkylating agents: An M‐FISH study
Authors: Andersen Mette K. , Christiansen Debes H. , Pedersen‐Bjergaard Jens
Published: January 2005

Multicolor fluorescence in situ hybridization (M‐FISH) was performed on bone marrow cells of 116 unselected cases of therapy‐related myelodysplasia (t‐MDS) or acute myeloid leukemia (t‐AML), and the results were compared with those of previously performed with G‐banding. Among 18 patients with a normal karyotype, no cryptic chromosome aberrations were observed with M‐FISH. In 56 patients with a previously solved abnormal karyotype, only 17 new aberrations were identified, whereas 153 new aberrations were detected by M‐FISH in 42 patients with a previously unsolved karyotype. In total, 112 of the new aberrations were unbalanced translocations, and only nine were balanced translocations. A clustering of breakpoints was observed in the centromeric or pericentromeric region of chromosomes 1, 5, 7, 13, 17, 21, and 22 in 48 of 98 patients with t‐MDS and t‐AML and an abnormal karyotype, and was related to previous therapy with alkylating agents. In seven of eight patients with chromosome derivatives containing material from three or more chromosomes or having sandwichlike chromosomes, those made up of several small interchanging layers of material from two chromosomes showed mutations of TP53. M‐FISH had little impact on the prognostic classification of t‐MDS and t‐AML, as only three patients changed prognostic groups as a result of M‐FISH. © 2005 Wiley‐Liss, Inc.
Location of Myc, Igh, and Igk on Robertsonian fusion chromosomes is inconsequential for Myc translocations and plasmacytoma development in mice, but Rb(6.15)‐carrying tumors prefer Igk–Myc inversions over translocations
Authors: Silva Santiago , Wiener Francis , Klein George , Janz Siegfried
Published: January 2005

The location of the Myc and immunoglobulin (Ig) loci on metacentric Robertsonian (Rb) fusion chromosomes may affect the development of mouse plasmacytomas (Pcts) by changing the probability with which chromosomal Myc–Ig translocations occur. To test this hypothesis, we induced Pcts in BALB/c (C) mice that carried Rb(4.12) and/or Rb(6.15) chromosomes. The Rb mice developed Pcts (n = 198) with similar onset and incidence to that in the inbred C mice. Karyotyping of 70 Rb–carrying Pcts demonstrated that in these tumors, just as in their counterparts in inbred C mice, the Igh heavy‐chain locus was translocated with Myc more often than was the Igk light‐chain locus. Pcts harboring Igh or Igk on normal and Rb chromosomes showed no bias toward either in generating Myc translocations. These findings indicated that the location of Myc, Igh, and Igk on normal or Rb chromosomes is inconsequential for Myc translocation and Pct development. In contrast, in Rb(6.15) mice, in which chromosomal inversions competed with chromosomal translocations for Igk–Myc juxtapositions, the former occurred more frequently than the latter in the resulting Pcts. This suggested that spatial proximity of Igk and Myc on the same chromosome facilitates the rearrangement of these loci. Myc translocation–dependent mouse Pct may provide a good model system for furthering our understanding of the relationship of higher‐order genome organization in the interphase nucleus, origin of chromosomal translocations, and development of cancer. Published 2005 Wiley‐Liss, Inc.
A cross‐linker‐sensitive myeloid leukemia cell line from a 2‐year‐old boy with severe Fanconi anemia and biallelic FANCD1/BRCA2 mutations
Authors: Meyer Stefan , Fergusson William D. , Oostra Anneke B. , Medhurst Annette L. , Waisfisz Quinten , de Winter Johan P. , Chen Fei , Carr Trevor F. , Clayton‐Smith Jill , Clancy Tara , Green Mike , Barber Lisa , Eden Osborn B. , Will Andrew M. , Joenje Hans , Taylor G. Malcolm
Published: January 2005

Fanconi anemia (FA) is a rare autosomal recessive disorder characterized by congenital and developmental abnormalities, hypersensitivity to DNA cross‐linking agents such as mitomycin C (MMC), and strong predisposition to acute myeloid leukemia (AML). In this article, we describe clinical and molecular findings in a boy with a severe FA phenotype who developed AML by the age of 2. Although he lacked a strong family history of cancer, he was subsequently shown to carry biallelic mutations in the FANCD1/BRCA2 gene. These included an IVS7 splice‐site mutation, which is strongly associated with early AML in homozygous or compound heterozygous carrier status in FA‐D1 patients. Myeloid leukemia cells from this patient have been maintained in culture for more than 1 year and have been designated as the SB1690CB cell line. Growth of SB1690CB is dependent on granulocyte macrophage colony stimulating factor or interleukin‐3. This cell line has retained its MMC sensitivity and has undergone further spontaneous changes in the spectrum of cytogenetic aberrations compared with the primary leukemia. This is the second AML cell line derived from an FA‐D1 patient and the first proof that malignant clones arising in FA patients can retain inherited MMC sensitivity. As FA‐derived malignancies are normally not very responsive to treatment, this implies there are important mechanisms of acquiring correction of the cellular FA phenotype that would explain the poor chemoresponsiveness observed in FA‐associated malignancies and might also play a role in the initiation and progression of cancer in the general population. © 2005 Wiley‐Liss, Inc.
Identification of differentially expressed genes in oral squamous cell carcinoma (OSCC): Overexpression of NPM, CDK1 and NDRG1 and underexpression of CHES1
Authors: Chang Joseph T. , Wang Hung‐Ming , Chang Ku‐Wei , Chen Wen‐Ho , Wen Ming‐Chun , Hsu Yuan‐Ming , Yung Benjamin Yat‐Ming , Chen I‐How , Liao Chun‐Ta , Hsieh Ling‐Ling , Cheng Ann‐Joy
Published: January 2005

To identify cellular genes that could potentially serve as predictive molecular markers for human oral cancer, we employed differential display analysis to compare the gene expression profiles between oral squamous cell carcinoma (OSCC) and histopathologically normal epithelium tissues. Comparative real‐time RT‐PCR was used to confirm the gene expression in 52 OSCC patients, and a 2‐fold difference was defined as over‐ or underexpression. A total of 7 genes were identified: NPM, CDK1, NDRG1, HMGCR, EF1A, NAC and CHES1. In the cancer tissues, NPM, CDK1 and NDRG1 were significantly overexpressed (an average of 7.6‐, 17.2‐ and 12.9‐fold, respectively), and CHES1 was underexpressed (15‐fold). The frequencies of the differential expression were 40, 56, 67 and 46%, respectively in NPM, CDK1, NDRG1 and CHES1. In Western blot analysis, the protein expressions of NPM, CDK1 and NDRG1 were also increased in the cancer tissues, consistent with the mRNA expression results. To further evaluate clinicopathological associations in these genes, Pearson chi‐square analysis was employed. Levels of CDK1 and NDRG1 were associated with poorly differentiated tumors (p = 0.043 and 0.023), suggesting that these genes participate in the mechanism of tumor transformation. Expressions of CDK1 and NDRG1, and CDK1 and CHES1 were mutually statistically correlated (p = 0.001 and 0.014), indicating that these genes share a very close regulatory relationship or interact synergistically in oncogenesis. In conclusion, we identified 7 genes that are differentially expressed in OSCC, and we provide the first evidence that NPM, CDK1 and NDRG1 are overexpressed and CHES1 is underexpressed in oral cancer. These results serve as a fundamental base for employing these genes in future clinical applications. © 2004 Wiley‐Liss, Inc.
Transcriptional profiling on chromosome 19p indicated frequent downregulation of ACP5 expression in hepatocellular carcinoma
Authors: Chan Kathy Y.‐Y. , Wong Nathalie , Lai Paul B.‐S. , Squire Jeremy A. , Macgregor Pascale F. , Beheshti Ben , Albert Monique , To Ka‐Fai , Johnson Philip J.
Published: January 2005

Chromosomal rearrangements unraveled by spectral karyotyping (SKY) indicated frequent chromosome 19 translocations in hepatocellular carcinoma (HCC). In an effort to characterize the aberrant 19 rearrangements in HCC, we performed positional mapping by fluorescence in‐situ hybridization (FISH) in 10 HCC cell lines. SKY analysis indicated structural rearrangements of chromosome 19 in 6 cell lines, 4 of which demonstrated recurring 19p translocations with different partner chromosomes. Using fluorescence‐labeled BAC probes, physical mapping indicated a breakpoint cluster between 19p13.12 and 19p12. A corresponding transcriptional mapping by cDNA array on 19p suggested the differential expression of a single downregulated gene ACP5 (tartrate‐resistant acid phosphatase type 5). Quantitative RT‐PCR confirmed the reduced expression of ACP5 and indicated a strong correlation of its repressed expression only in cell lines that contain a 19p rearrangement (p = 0.004). We further examined the expression of ACP5 in a cohort of 82 primary tumors and 74 matching nonmalignant liver tissues. In the primary HCC examined, a reduction of ACP5 transcripts by 2 to as much as 1,000‐fold was suggested in 67% of tumors (55/82 cases). When compared to adjacent nonmalignant tissues, 46% of tumors (34/74 cases) demonstrated a lower expression level (p = 0.015). On closer examination, a high significance of ACP5 repression was suggested in the cirrhotic HCC subgroup that was derived from chronic hepatitis B infected patients (55%; 30/54 cases; p = 0.001). Functional examination of ACP5 ectopic expression in HCC cells further demonstrated a significant growth inhibitory effect of ACP5 on tumor cell survival (p < 0.001). In our study, the novel finding of common ACP5 downregulation in HCC may provide basis for further investigations on the role of acid phosphatase in hepatocarcinogenesis. © 2004 Wiley‐Liss, Inc.
Residential radon exposure, diet and lung cancer: A case‐control study in a Mediterranean region
Authors: Bochicchio Francesco , Forastiere Francesco , Farchi Sara , Quarto Maria , Axelson Olav
Published: January 2005

We performed a case‐control study in Lazio, a region in central Italy characterized by high levels of indoor radon, Mediterranean climate and diet. Cases (384) and controls (404) aged 35–90 years were recruited in the hospital. Detailed information regarding smoking, diet and other risk factors were collected by direct interview. Residential history during the 30‐year period ending 5 years before enrolment was ascertained. In each dwelling, radon detectors were placed in both the main bedroom and the living room for 2 consecutive 6‐month periods. We computed odds ratios (ORs) and 95% confidence intervals (CIs) for time‐weighted radon concentrations using both categorical and continuous unconditional logistic regression analysis and adjusting for smoking, diet and other variables. Radon measurements were available from 89% and 91% of the time period for cases and controls, respectively. The adjusted ORs were 1.30 (1.03–1.64), 1.48 (1.08–2.02), 1.49 (0.82–2.71) and 2.89 (0.45–18.6) for 50–99, 100–199, 200–399 and 400+ Bq/m3, respectively, compared with 0−49 Bq/m3 (OR = 1; 0.56–1.79). The excess odds ratio (EOR) per 100 Bq/m3 was 0.14 (−0.11, 0.46) for all subjects, 0.24 (−0.09, 0.70) for subjects with complete radon measurements and 0.30 (−0.08, 0.82) for subjects who had lived in 1 or 2 dwellings. There was a tendency of higher risk estimates among subjects with low‐medium consumption of dietary antioxidants (EOR = 0.32; −0.19, 1.16) and for adenocarcinoma, small cell and epidermoid cancers. This study indicates an association, although generally not statistically significant, between residential radon and lung cancer with both categorical and continuous analyses. Subjects with presumably lower uncertainty in the exposure assessment showed a higher risk. Dietary antioxidants may act as an effect modifier. © 2004 Wiley‐Liss, Inc.
Smokeless tobacco use and risk of cancer of the pancreas and other organs
Authors: Boffetta Paolo , Aagnes Bjarte , Weiderpass Elisabete , Andersen Aage
Published: January 2005

Limited data are available on the carcinogenicity of smokeless tobacco products in organs other than the mouth. Snus is a smokeless tobacco product widely used in Norway. We studied 10,136 Norwegian men enrolled since 1966 in a prospective cohort study, 31.7% of whom were exposed to snus. The relative risk of pancreatic cancer for snus use was 1.67 (95% confidence interval [CI] = 1.12, 2.50); that of oral and pharyngeal cancer was 1.10 (95% CI = 0.50, 2.41), that of esophageal cancer was 1.40 (95% CI = 0.61, 3.24), and that of stomach cancer was 1.11 (95% CI = 0.83, 1.48). The relative risks of cancers of the lung (either all histological types or adenocarcinoma), urinary bladder and kidney were not increased among snus users. The increase in the relative risk of pancreatic cancer was similar in former and current snus users and was restricted to current tobacco smokers. Our study suggests that smokeless tobacco products may be carcinogenic on the pancreas. Tobacco‐specific N‐nitrosamines are plausible candidates for the carcinogenicity of smokeless tobacco products in the pancreas. © 2004 Wiley‐Liss, Inc.
Use of a transgenic mouse model to identify markers of human lung tumors
Authors: Linnerth Nicolle M. , Sirbovan Kelly , Moorehead Roger A.
Published: January 2005

Lung cancer remains the leading cause of cancer related deaths worldwide. Despite advances in detection technologies, most patients diagnosed with lung cancer already harbor metastatic lesions. Because early detection is one of the primary determinants of patient outcome, a transgenic mouse model of lung cancer was utilized to identify markers of early lung tumors in humans. DNA microarray analysis of lung tumors arising in MMTV‐IGF‐II transgenic mice showed 9 genes consistently elevated in the murine lung tumors. Western blot analyses confirmed that several of these proteins were elevated in the lung tumors and immunohistochemical analyses identified 3 proteins, microsomal glutathione‐S‐transferase 1 (Mgst1), cathepsin H and syndecan 1 as being consistently elevated in the murine lung tumors compared to non‐tumor bearing transgenic lung tissue and normal lung tissue surrounding the tumor. These 3 proteins were also elevated in human lung adenocarcinoma and squamous cell carcinomas. Importantly, the proteins were elevated in early stage, node negative tumors indicating their ability to detect early lung lesions that would be amenable to surgical resection. Therefore, our findings indicate that Mgst1, cathepsin H and syndecan 1 should be further evaluated as markers capable of identifying patients with early stage lung tumors. © 2004 Wiley‐Liss, Inc.
Intrinsic chemotherapy resistance to the tubulin‐binding antimitotic agents in renal cell carcinoma
Authors: Ferguson Roisean E. , Jackson Sharon M. , Stanley Anthea J. , Joyce Adrian D. , Harnden Patricia , Morrison Ewan E. , Patel Poulam M. , Phillips Roger M. , Selby Peter J. , Banks Rosamonde E.
Published: January 2005

Renal cancer is one of the most chemoresistant tumor types. Using a panel of 10 established renal cancer cell lines that have not been subjected to prior drug selection, the range of functional resistance phenotypes to the tubulin‐binding agents paclitaxel, vinblastine, vincristine and patupilone (epothilone B, EPO906) was determined, together with expression of P‐glycoprotein (PgP), multidrug resistance associated protein‐2 (MRP2) and major vault protein (MVP) proteins. The IC50 values for vincristine correlated positively with PgP expression (r = 0.73; p = 0.031), with values for paclitaxel and vinblastine just failing to reach significance. A significant positive correlation was observed for sensitivity to paclitaxel and MRP2 expression only (r = 0.8; p = 0.013). MVP expression did not correlate with sensitivity to any of the drugs examined. All cell lines exhibited much greater sensitivity to patupilone, demonstrating for the first time the potential use of patupilone in this cancer. In tissue samples from chemotherapy‐naive renal cell carcinoma (RCC) patients, marked downregulation or absence of PgP in many tumor cells with expression levels more similar to sensitive cell lines rather than the resistant lines was seen. Similarly, MRP2 was absent or only weakly present in tumor cells, whereas MVP was very strongly upregulated in most tumor samples. This study illustrating discrepancies between results exclusively based on studies in cell lines and findings in vivo suggests that the role of PgP and MRP2 in intrinsic resistance in RCC in vivo may be less than expected from the in vitro findings and supports a potential role for MVP on the basis of in vivo expression studies. © 2004 Wiley‐Liss, Inc.
Single‐cell analysis of loss of heterozygosity at the ATM gene locus in Hodgkin and Reed‐Sternberg cells of Hodgkin's lymphoma: ATM loss of heterozygosity is a rare event
Authors: Lespinet Virginie , Terraz Fanny , Recher Christian , Campo Elias , Hall Janet , Delsol Georges , Al Saati Talal
Published: January 2005

Hodgkin's lymphoma (HL) is a lymphoid malignancy characterized by the presence of rare neoplastic cells, Hodgkin and Reed‐Sternberg (HRS) cells, scattered among a predominant population of inflammatory cells. On the basis of previously reported cytogenetic analyses, the ATM (ataxia‐telangiectasia mutated) gene at 11q22‐23 has been implicated in the etiology of HL. We therefore developed a single‐cell PCR approach to detect ATM loss of heterozygosity (LOH) in HRS cells. Three microsatellites were investigated; 1 localized inside the ATM gene and the remaining 2 in close proximity. In 2 of the 15 lymph node samples, an allelic loss of the ATM gene locus was detected. ATM protein expression was examined in 8 cases (including 1 of the 2 cases with LOH) by immunohistochemistry. In the case associated with an allelic loss, the ATM protein was absent in the HRS cells, whereas in the 7 remaining cases, without detectable LOH at the ATM locus, nuclear ATM expression was observed. In the 2 HL cases with LOH, the ATM gene was sequenced following whole genome amplification of DNA isolated from microdissected HRS cells. In 1 of these 2 cases, a splice site mutation in the second ATM allele was found. This mutation could generate a premature termination codon leading to a marked instability and a rapid degradation of the resulting ATM mRNA transcripts. This latter event could explain the loss of the expression of the ATM protein in HRS cells as detected by immunohistochemistry in this particular case. As previously reported in some B‐cell lymphomas, our results suggest that ATM genetic anomalies could play a role in the pathogenesis of a subset of HL cases. © 2004 Wiley‐Liss, Inc.
Skeletal health in postmenopausal survivors of early breast cancer
Authors: Mackey John R. , Joy Anil A.
Published: January 2005

Estrogen plays an important role in the skeletal health of all women. Many therapies used in the treatment of breast cancer reduce estrogen levels and have the potential to affect bone negatively by increasing the risk of osteoporosis and associated bone fractures. The long‐term effects of systemic endocrine therapy on bone, therefore, are an important consideration in the adjuvant setting. Tamoxifen has been shown to have a moderate protective effect on postmenopausal bone due to its partial estrogen agonist activity; however, its long‐term use is potentially associated with negative side effects, such as an increased risk of thromboembolic disease and endometrial cancer. Newer agents, the third‐generation aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, for example, do not possess estrogen agonist effects and have improved breast cancer outcomes when compared to the standard 5 years of tamoxifen. However, patients treated with adjuvant AIs have been shown to have an increased incidence of osteoporosis and osteoporotic fractures. In order to select the optimal adjuvant therapy for each patient, it is important to assess the overall risk:benefit ratio for each endocrine strategy. All postmenopausal women should follow published guidelines to assess the risk of osteoporosis and, where appropriate, they should receive bone mineral density monitoring. Postmenopausal women with breast cancer who are at increased risk of osteoporotic fracture should be identified and managed with appropriate nonpharmacologic and pharmacologic measures. © 2004 Wiley‐Liss, Inc.