bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on the morphology of the hydrophobically‐modified polyelectrolyte in aqueous solution by AFM measurements
Authors: Ye Lin , Huang Ronghua , Hoffmann Heinz , Wang Chun
Published: May 2004

This work focuses on the AFM study of the aggregation morphology and association mechanism of the hydrophobically‐association water‐soluble polymer P (AM‐AA‐BPAM) in aqueous solution. It shows that the P (AM‐AA‐BPAM) molecule chain, which has hydrophobic and hydrophilic ionic groups, forms the “spherical” aggregations as micelles below 0.2 g · dL−1, and then connect each other to form the string‐like aggregations, which produce large viscosity for the polymer solution. It is also coincident with the FCS, DLS, and viscosity study result. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 1175–1178, 2004
Drug complexation and physicochemical properties of vinylpyrrolidone‐N,N′‐dimethylacrylamide copolymers
Authors: de Queiroz Alvaro A. A. , França Écio J. , Abraham Gustavo A. , Roman Julio San
Published: May 2004

Solid dispersions of the nonsteriodal antiinflammatory drug (NSAID) 2′,4′‐difluoro‐4‐hydroxy‐(1,1′‐biphenyl)‐3‐carboxylic acid (DIF) with the water‐soluble random copolymer poly(N‐vinyl‐2‐pyrrolidone‐co‐N,N′‐dimethylacrylamide) (VP‐co‐DMAm) were prepared by the solvent method (coevaporates) and melting DIF/VP‐co‐DMAm (cofused) physical mixtures. Differential scanning calorimetry (DSC), infrared spectroscopy (FTIR), and X‐ray diffraction (XRD) were used to elucidate the possible interaction between the NSAID drug and VP‐co‐DMAm in cofused and coevaporated polymer–drug solid dispersions. The XRD and FTIR studies suggest the presence of physical interactions with formation of a charge transfer complex between DIF and the VP‐co‐DMAm copolymers as a consequence of the coevaporation or cofusion processes. In solution, dynamic and equilibrium solubility studies were determined to elucidate the mechanism of interaction between DIF and VP‐co‐DMAm copolymers. Thermodynamics data about the DIF: VP‐co‐DMAm dissolution process indicate that the coevaporated systems are more stable that the cofused systems. The dissolution of the cofused and coevaporated systems was diffusion controlled and the dissolution kinetics followed the Noyes–Whitney and the Levich equations. Molecular simulations using semiempirical quantum chemical calculations reinforce the experimental results, suggesting that the improvement in the DIF solubility could be attributed to the charge transfer complex formation between the drug and VP‐co‐DMAm copolymers. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 1337–1347, 2004
Influence of LiClO4 on the thermal, mechanical, and morphological properties of P(DMS‐co‐EO)/ P(EPI‐co‐EO) blends
Authors: Fonseca C. P. , Guedes C. G. F. , Rosa D. S. , Neves S.
Published: May 2004

The UV‐vis absorption, thermal analysis, ionic conductivity, mechanical properties, and morphology of a blend of poly(dimethylsiloxane‐co‐ethylene oxide) [P(DMS‐co‐EO)] and poly(epichlorohydrin‐co‐ethylene oxide) [P(EPI‐co‐EO)] (P(DMS‐co‐EO)/P(EPI‐co‐EO) ratio of 15/85 wt %) with different concentrations of LiClO4 were studied. The maximum ionic conductivity (σ = 1.2 × 10−4 S cm−1) for the blend was obtained in the presence of 6% wt LiClO4. The crystalline phase of the blend disappeared with increasing salt concentration, whereas the glass transition temperature (Tg) progressively increased. UV‐vis absorption spectra for the blends with LiClO4 showed a transparent polymer electrolyte in the visible region. The addition of lithium salt decreased the tensile strength and elongation at break and increased Young's modulus of the blends. Scanning electron microscopy showed separation of the phases between P(DMS‐co‐EO) and P(EPI‐co‐EO), and the presence of LiClO4 made the blends more susceptible to cracking. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 1230–1235, 2004
Dynamic mechanical thermal analysis of thermally stable and thermally reactive network polymers
Authors: Cook W. D. , Scott T. F. , Quay‐Thevenon S. , Forsythe J. S.
Published: May 2004

The temperature and frequency dependence of the dynamic mechanical properties in the glass transition was studied for a series of partially cured thermally reactive networks (low temperature cured epoxy and a dimethacrylate photocured with a conventional initiator) and more thermally stable networks (high temperature cured epoxy and two dimethacrylates photocured with a photoiniter1). The viscoelastic behavior in the transition region of the former networks changed during the experiment due to additional cure, whereas the thermally stable networks enabled the study of the effect of conversion on the transition region. The glass transition temperatures showed 1 : 1 relationships with the isothermal curing temperatures and were correlated with the degree of conversion. The breadth of the glass transition, as determined from the real and loss moduli, tan δ, and the loss compliance in the temperature and frequency domains, was found to be greater for the dimethacrylate networks than for the epoxy networks. The breadth of the transition for the dimethacrylates was not significantly dependent on the degree of cure. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 1348–1359, 2004
A kinetic investigation of the in situ polymerization of methyl methacrylate under supercritical fluid CO2 conditions using high‐pressure DSC
Authors: Lu Shiying , Zhang Zhiyi , Nawaby A. Victoria , Day Michael
Published: May 2004

The polymerization kinetics of methyl methacrylate (MMA) under supercritical fluid CO2 was studied by using high‐pressure DSC. The results indicate that CO2 can significantly reduce the cage effect and improve the chain propagation reactions, with the observed solvent‐like effects being enhanced by increased CO2 pressures. The polymerization of MMA under isothermal conditions and 56 atm of CO2 was characterized by a first‐order kinetic rate expression over the conversion range 20–80%. The apparent activation energy for the reaction was found to be 51.6 kJ/mol, which is less than the value reported under ambient conditions (68.2 kJ/mol). The polymerization kinetics were also evaluated under nonisothermal conditions. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 1236–1239, 2004
Bithiazole‐containing polymeric complex and PVA composite film: Preparation and magnetic properties
Authors: Lin Caiping , Sun Weilin , Jiang Liming , Wang Liqun , Shen Zhiquan
Published: May 2004

Two novel bithiazole‐containing polyamides, DClAI and DTTPA, and their complexes were synthesized by condensation and complexation. Novel homogeneous composite films were prepared by in situ blending these complexes with polyvinyl alcohol. These polymeric complexes and composite films were characterized by FTIR. The magnetic properties of the complex and its related composite film were measured using a physical property measurement system. It was found that the properties of films are similar to those of their related polymeric complexes. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 1264–1270, 2004
In vitro laser ablation of laboratory developed biofilms using an Nd:YAG laser of 532 nm wavelength
Authors: Nandakumar Kanavillil , Obika Hideki , Utsumi Akihiro , Ooie Toshihiko , Yano Tetsuo
Published: May 2004

We studied the laser ablation of laboratory‐developed biofilm on titanium and glass surfaces. Specifically, Pseudoalteromonas carrageenovora, a marine biofilm forming bacterium was used to generate laboratory biofilm. Two fluences, 0.05 and 0.1 J/cm2 and three durations of irradiation, 30 s, 5 min, and 10 min were tested using an Nd;YAG laser of 532 nm wavelength (in the green light area). Nonirradiated coupons with biofilm served as control. The biofilm removal efficiency increased with the increase in laser fluence and duration of irradiation. The maximum biofilm area cover on control coupons of glass and titanium was 62.5 and 76.0%, respectively. Upon irradiation with fluence 0.1 J/cm2 for the very short duration of 30 s, this reduced to 5.6 and 12.4% and at 10 min to 2.17 and 0.7% on glass and titanium coupons, respectively, while the controls did not show any reductions (62.5 and 76.0% respectively, for glass and titanium coupons). The biofilm TRC (Total Resuscitated Cells) reduction during this period was even more prominent than the area cover, indicating that the remaining biofilm portions on coupons after irradiation were largely composed of dead bacterial cells. The TRC in the irradiation chamber medium for short durations of irradiation showed a significant increase, indicating that the laser irradiation removed live bacteria from the biofilm. The re‐growth of the resuscitated cells showed they could grow like the control cells but with a significant lag. The laser's efficiency in the removal of biofilm was better seen on titanium coupons than on glass. Our results showed that a low‐ power pulsed laser irradiation could be used to remove biofilm formed on hard surfaces. © 2004 Wiley Periodicals, Inc.
Direct Synthesis of Tricarbonyl(cyclopentadienyl)rhenium and Tricarbonyl(cyclopentadienyl)technetium Units from Ferrocenyl Moieties − Preparation of 17α‐Ethynylestradiol Derivatives Bearing a Tricarbonyl(cyclopentadienyl)technetium Group
Authors: Masi Stéphane , Top Siden , Boubekeur Leila , Jaouen Gérard , Mundwiler Stefan , Spingler Bernhard , Alberto Roger
Published: May 2004

The preparation of new tricarbonyl(cyclopentadienyl)rhenium and tricarbonyl(cyclopentadienyl)technetium derivatives is described. The approach used was applied to a cold target model, 17α‐ethynylestradiol substituted at the 17α position by a ketotricarbonyl(cyclopentadienyl)rhenium group. The novel organometallic reaction applied here, when extended to potential radiopharmaceuticals, consists of a cyclopentadienyl‐ligand transfer between ketoferrocenes and fac‐[99mTc(H2O)3(CO)3]+ in a water/DMSO 1:1 mixture. This reaction lead to the synthesis of a new estradiol derivative, labeled with 99mTc. The synthesis of another product was performed by using [99TcCl3(CO)3]2− as the Tc precursor and its X‐ray crystal structure was determined. In each case high yields were obtained. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Lanthanide(II) and ‐(III) Porphyrinogens − Rational Synthesis and Derivatisation of Mononuclear, Alkali‐Metal‐Free Lanthanide(II) and ‐(III) meso‐Octaalkylporphyrinogen Complexes
Authors: Wang Jun , Dick Andrew K. J. , Gardiner Michael G. , Yates Brian F. , Peacock Evan J. , Skelton Brian W. , White Allan H.
Published: May 2004

Modifying the porphyrinogen framework in lanthanide porphyrinogen complexes by trans‐N,N′‐dimethylation results in SmII and SmIII derivatives that are remarkably simple in structure and formulation, and are amenable to highly controllable further reaction chemistry. The SmII bis(tetrahydrofuran) adduct, SmIII chloride and bis(trimethylsilyl)amide complexes have been synthesised and characterised by elemental analysis, 1H and 13C NMR spectroscopy and X‐ray crystal structure determinations. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Antioxidant activity of phenolic compounds in sunflower oil‐in‐water emulsions containing sodium caseinate and lactose
Authors: Velasco Joaquín , Dobarganes M. Carmen , Márquez‐Ruiz Gloria
Published: May 2004

The aim of this work was to study the evolution of oxidation and the efficiency of phenolic antioxidants in sunflower oil‐in‐water emulsions containing sodium caseinate and lactose (Cas‐Lac) or stabilized by Tween‐20 (T‐20). Two groups of phenolic antioxidants which are structurally similar were tested, i.e. (1) α‐tocopherol and its water‐soluble analogue, Trolox; and (2) gallic acid and its ester derivatives propyl gallate and dodecyl gallate. Emulsion samples were oxidized at 40 °C and the progress of oxidation was followed through quantitation of oxidized triacylglycerol monomers, dimers and oligomers. Results showed that Cas‐Lac emulsions were more stable to oxidation than T‐20 emulsions. In both types of emulsions, the most protective antioxidants were the compounds of lower polarity, namely, α‐tocopherol and dodecyl gallate. It was also found that substantial amounts of α‐tocopherol coexisted with significant polymerization, which was indicative of the heterogeneity of oxidation, i.e. differences of oxidation rate in oil droplets.
The effect of cooking and storage on the fatty acid profile of chicken breast
Authors: Conchillo Ana , Ansorena Diana , Astiasarán Iciar
Published: May 2004

The modification of the lipid profile of chicken breast after being cooked (grilled or roasted) and stored under different conditions (refrigeration Ta 4 °C t = 6 d, or freezing Ta‐18 °C t = 3 months, in aerobic or vacuum conditions) was studied. Grilling increased significantly the unsaturated/saturated (2.7) and polyunsaturated/saturated (1.4) ratios of fatty acids in comparison to raw samples (U/S = 1.7, P/S = 0.6) as a consequence of the use of sunflower oil. However, roasted samples did not significantly differ in these ratios (U/S = 1.8, P/S = 0.7) from raw samples. Fresh and stored raw and roasted samples did not show differences when a multivariate analysis was applied, although some significant differences were observed in their fatty acid profile. Frozen grilled samples (both aerobic and vacuum packed) showed differences from immediately cooked (t = 0) and refrigerated grilled samples.
Solvent and enzymatic extraction of Safou and Kolo oils
Authors: Dzondo‐Gadet Michel , Nzikou Jean Mathurin , Kimbonguila André , Linder Michel , Desobry Stéphane
Published: May 2004

Safou (Dacryodes edulis) pulp oil became a new hope for fragile economics of central Africa countries. Raphia sese palm tree (Kolo) produces also an edible vegetable oil of well nutritious value. Various extraction methods were checked for the best yields. By soxhlet extractor using petroleum ether best yields were attained (47% for Safou and 52% for Kolo; dry weight) followed by the Bligh and Dyer method (43.2% for Safou and 50.8% for Kolo). No further improvement was obtained by the enzymatic treatment with Viscozym L (42% for Safou, 51.3% for Kolo). The application of enzyme added to the preservation of oil from oxidation during extraction process.
Structure and transformation of low‐temperature phases of 1,3‐distearoyl‐2‐oleoyl glycerol
Authors: Mykhaylyk Oleksandr O. , Castelletto Valeria , Hamley Ian W. , Povey Malcolm J. W.
Published: May 2004

Polymorphic transformations of 1,3‐distearoyl‐2‐oleoyl glycerol (SOS) at low temperatures (10 °C–30 °C) have been studied by time‐resolved synchrotron X‐ray diffraction (XRD) measurements at small and wide angles. Three structures have been identified: α‐phase structure forms by quenching to 10 °C from the liquid state, a metastable structure formed simultaneously with α‐phase and γ‐phase formed at 30 °C during α‐melt‐mediated crystallisation as well as at the pre‐melting temperature (22.5 °C) of the α‐phase when the coexistence of two phases (α and γ) is observed. The metastable structure produces three broad peaks in XRD patterns at small angles (one strong and two weak peaks corresponding to d‐spacings of ∼4 nm, ∼12 nm and ∼1.5 nm respectively) and a peak in X‐ray diffraction patterns at wide angles (0.42 nm). A model is proposed for the metastable structure based on a combination of double‐ and triple‐chain packing of SOS molecules due to the similar length of alkyl chains (stearoyl and oleoyl) in the molecules.
Numerical analysis of moving interfaces using a level set method coupled with adaptive mesh refinement
Authors: Kohno Haruhiko , Tanahashi Takahiko
Published: May 2004

A novel numerical scheme is developed by coupling the level set method with the adaptive mesh refinement in order to analyse moving interfaces economically and accurately. The finite element method (FEM) is used to discretize the governing equations with the generalized simplified marker and cell (GSMAC) scheme, and the cubic interpolated pseudo‐particle (CIP) method is applied to the reinitialization of the level set function. The present adaptive mesh refinement is implemented in the quadrangular grid systems and easily embedded in the FEM‐based algorithm. For the judgement on renewal of mesh, the level set function is adopted as an indicator, and the threshold is set at the boundary of the smoothing band. With this criterion, the variation of physical properties and the jump quantity on the free surface can be calculated accurately enough, while the computation cost is largely reduced as a whole. In order to prove the validity of the present scheme, two‐dimensional numerical simulation is carried out in collapse of a water column, oscillation and movement of a drop under zero gravity. As a result, its effectiveness and usefulness are clearly shown qualitatively and quantitatively. Among them, the movement of a drop due to the Marangoni effect is first simulated efficiently with the present scheme. Copyright © 2004 John Wiley & Sons, Ltd.
Generalized fourier analyses of the advection–diffusion equation—Part II: two‐dimensional domains
Authors: Voth Thomas E. , Martinez Mario J. , Christon Mark A.
Published: May 2004

Part I of this work presents a detailed multi‐methods comparison of the spatial errors associated with the one‐dimensional finite difference, finite element and finite volume semi‐discretizations of the scalar advection–diffusion equation. In Part II we extend the analysis to two‐dimensional domains and also consider the effects of wave propagation direction and grid aspect ratio on the phase speed, and the discrete and artificial diffusivities. The observed dependence of dispersive and diffusive behaviour on propagation direction makes comparison of methods more difficult relative to the one‐dimensional results. For this reason, integrated (over propagation direction and wave number) error and anisotropy metrics are introduced to facilitate comparison among the various methods. With respect to these metrics, the consistent mass Galerkin and consistent mass control‐volume finite element methods, and their streamline upwind derivatives, exhibit comparable accuracy, and generally out‐perform their lumped mass counterparts and finite‐difference based schemes. While this work can only be considered a first step in a comprehensive multi‐methods analysis and comparison, it serves to identify some of the relative strengths and weaknesses of multiple numerical methods in a common mathematical framework. Published in 2004 by John Wiley & Sons, Ltd.
Consistent hybrid finite volume/element formulations: model and complex viscoelastic flows
Authors: Chandio M. S. , Sujatha K. S. , Webster M. F.
Published: May 2004

The accuracy and consistency of a new cell‐vertex hybrid finite element/volume scheme are investigated for viscoelastic flows. Finite element (FE) discretization is employed for the momentum and continuity equation, with finite volume (FV) applied to the constitutive law for stress. Here, the interest is to explore the consequences of utilizing conventional cell‐vertex methodology for an Oldroyd‐B model and to demonstrate resulting drawbacks in the presence of complex source terms on structured and unstructured grids. Alternative strategies worthy of consideration are presented. It is demonstrated how high‐order accuracy may be achieved in steady state by respecting consistency in the formulation. Both FE and FV spatial discretizations are embedded in the scheme, with FV triangular sub‐cells referenced within parent triangular finite elements. Both model and complex flow problems are selected to quantify and assess accuracy, appealing to analysis and experimental validation. The test problem is that of steady sink flow, a pure extensional flow, which reflects some of the numerical difficulties involved in solving more generalized viscoelastic flows, where both source and flux terms may contribute equally to stress propagation. In addition, a complex transient filament‐stretching flow is chosen to compute the evolution of stress fields within liquid bridges. Shortcomings of the various stress upwinding schemes are discussed in this context, whilst dealing with such free‐surface type problems. Here, stress fluctuation distribution alone is advocated, and a Lax‐scheme is found to deliver accuracy and stability to the computational results, comparing well with the literature. Copyright © 2004 John Wiley & Sons, Ltd.
Zero mass error using unsteady wetting–drying conditions in shallow flows over dry irregular topography
Authors: Brufau P. , García‐Navarro P. , Vázquez‐Cendón M. E.
Published: May 2004

A wetting–drying condition (WDC) for unsteady shallow water flow in two dimensions leading to zero numerical error in mass conservation is presented in this work. Some applications are shown which demonstrate the effectiveness of the WDC in flood propagation and dam break flows over real geometries. The WDC has been incorporated into a cell centred finite volume method based on Roe's approximate Riemann solver across the edges of both structured and unstructured meshes. Previous wetting–drying condition based on steady‐state conditions lead to numerical errors in unsteady cases over configurations with strong variations on bed slope. A modification of the wetting–drying condition including the normal velocity to the cell edge enables to achieve zero numerical errors. The complete numerical technique is described in this work including source terms discretization as a complete and efficient 2D river flow simulation tool. Comparisons of experimental and numerical results are shown for some of the applications. Copyright © 2004 John Wiley & Sons, Ltd.
Enhanced in vitro invasiveness and drug resistance with altered gene expression patterns in a human lung carcinoma cell line after pulse selection with anticancer drugs
Authors: Liang Yizheng , O'Driscoll Lorraine , McDonnell Susan , Doolan Padraig , Oglesby Irene , Duffy Kieran , O'Connor Robert , Clynes Martin
Published: May 2004

The human lung carcinoma cell line DLKP was exposed to sequential pulses of 10 commonly used chemotherapeutic drugs (VP‐16, vincristine, taxotere, mitoxantrone, 5‐fluorouracil, methotrexate, CCNU, BCNU, cisplatin and chlorambucil); resulting cell lines exhibited resistance to the selecting agents (ranging approx. 1.5‐ to 36‐fold) and, in some cases, cross‐resistance to methotrexate (approx. 1.4‐ to 22‐fold), vincristine (1.6‐ to 262‐fold), doxorubicin (Adriamycin, approx. 1.1‐ to 33‐fold) and taxotere (approx. 1.1‐ to 36‐fold). Several of the variants displayed collateral sensitivity to cisplatin. A marked increase in in vitro invasiveness and motility was observed with variants pulsed with mitoxantrone, 5‐fluorouracil, methotrexate, BCNU, cisplatin and chlorambucil. There was no significant change in invasiveness of cells pulsed with VP‐16, vincristine, taxotere or CCNU. All of the pulse‐selected variants showed elevated levels of MDR‐1/P‐gp protein by Western blot analysis, although mdr‐1 mRNA levels were not increased (except for DLKP‐taxotere). In DLKP‐taxotere, MRP1 protein levels were also greatly elevated, but mrp1 mRNA levels remained unchanged. BCRP was upregulated in DLKP‐mitoxantrone at both the mRNA and protein levels. Gelatin zymography, Western blot and RT‐PCR showed that DLKP and its variants secreted MMPs 2, 9 and 13. MMP inhibition assays suggested that MMP‐2 plays a more important role than MMPs 9 and 13 in cell invasion of these DLKP drug‐resistant variants in vitro. These results indicate that drug exposure may induce not only resistance but also invasiveness in cancer cells. © 2004 Wiley‐Liss, Inc.
CNTO 328, a monoclonal antibody to IL‐6, inhibits human tumor‐induced cachexia in nude mice
Authors: Zaki Mohamed H. , Nemeth Jeffrey A. , Trikha Mohit
Published: May 2004

IL‐6 is a multifunctional cytokine implicated in several cancers. IL‐6 is a growth factor for certain tumors and contributes to drug resistance, cachexia and bone resorption. Cachexia is characterized by progressive weight loss and depletion of host reserves of adipose tissue and skeletal muscle. We have developed CNTO 328 (cCLB8), a human–mouse chimeric MAb to IL‐6 (Kd approx. 10−12 M) that inhibits IL‐6 function. A phase I study with CNTO 328 in multiple myeloma patients demonstrated that the antibody was safe and had a circulating half‐life of approximately 17 days. Since IL‐6 is implicated in cachexia, we hypothesized that CNTO 328 could inhibit tumor‐induced cachexia. We used 2 human tumor‐induced cachexia models in nude mice. In the first model, human melanoma cells were inoculated in female nude mice. Control treated animals lost 19% (±7.7%) body weight from day 0 to day 31, whereas CNTO 328 (10 mg/kg)–treated animals lost only 1.5% (±1.3%) body weight from day 0 to day 31 (p = 0.023). In the second cachexia model, human prostate tumor cells were injected into male nude mice. By day 29, control treated animals lost 6% (±3.5%) body weight, whereas CNTO 328 (10 mg/kg)–treated animals gained 7% (±4%) body weight (p = 0.01). Since CNTO 328 blocks human IL‐6 but not mouse IL‐6, the data indicate that tumor cell–secreted IL‐6 directly contributes to body weight loss, highlighting the potential role for CNTO 328 as an anticachectic agent. © 2004 Wiley‐Liss, Inc.
Metalloproteinase inhibition augments antitumor efficacy of the anti‐CD30 immunotoxin Ki‐3(scFv)‐ETA′ against human lymphomas in vivo
Authors: Matthey Baerbel , Borchmann Peter , Schnell Roland , Tawadros Samir , Lange Hans , Huhn Michael , Klimka Alexander , Tur Mehmet K. , Barth Stefan , Engert Andreas , Hansen Hinrich P.
Published: May 2004

There is increasing evidence that the shedding of extracellular antigen domains impedes selective immunotherapy. One example is CD30, which is overexpressed on the surface of malignant lymphoma cells and has been identified as a promising target for antibody‐based immunotherapy. However, CD30 is cleaved from the surface of target cells and the resulting soluble ectodomain (sCD30) is protecting the cells from antibody binding. Shedding can be inhibited by hydroxamate inhibitors of metalloproteinases such as BB‐3644. We thus evaluated the influence of BB‐3644 on the efficacy of the anti‐CD30 single‐chain immunotoxin Ki‐3(scFv)‐ETA′. In vitro, the addition of BB‐3644 augmented the antitumor effect of Ki‐3(scFv)‐ETA′ against Hodgkin‐derived L540Cy cells by a factor of 2.75. Severe combined immunodeficiency (SCID) mice challenged with CD30‐positive L540Cy cells were treated with the immunotoxin. One single nontoxic dose of BB‐3644 increased the mean survival time of animals treated concomitantly with Ki‐3(scFv)‐ETA′ to 93 days as compared with 35 days in the control (p = 0.0017). When BB‐3644 was continuously delivered using subcutaneously implanted pumps, this effect was even more pronounced with no observed tumor growth in the animals within 200 days. Thus, concomitant application of metalloproteinase inhibitors might become clinically relevant in antibody‐based immunotherapy against targets known to be shed from tumor cells. © 2004 Wiley‐Liss, Inc.
Expression in bladder transitional cell carcinoma by real‐time quantitative reverse transcription polymerase chain reaction array of 65 genes at the tumor suppressor locus 9q34.1‐2: Identification of 5 candidates tumor suppressor genes
Authors: Amira Najla , Cancel‐Tassin Géraldine , Bernardini Stéphane , Cochand‐Priollet Béatrix , Bittard Hugues , Mangin Philippe , Fournier Georges , Latil Alain , Cussenot Olivier
Published: May 2004

Frequent deletions on 9q34.1‐2 were reported in bladder transitional cell carcinoma. High deletion mapping studies delimited a critical interval between markers D9S61 and D9S66, which is highly susceptible to contain a tumor suppressor gene. Expression level of the 65 genes localized in this region was analyzed by real‐time quantitative RT‐PCR, comparing tumor to normal urothelium. Five genes exhibited a significantly reduced expression level: C9orf9, KIAA0625, ABL1, LAMC3 and KIAA1857‐netrin‐G2, which exhibited the most significant downregulation (p=0.0007). KIAA1857‐netrin‐G2 belongs to the netrins and might then be a tumor suppressor gene in bladder cancer, as netrin1 receptor DCC has been implicated in tumorigenesis. © 2004 Wiley‐Liss, Inc.
Antimetastatic activity of the photodynamic agent hypericin in the dark
Authors: Blank Michael , Lavie Gad , Mandel Mathilda , Hazan Sadick , Orenstein Arie , Meruelo Daniel , Keisari Yona
Published: May 2004

A unique property of the photodynamic signal transduction inhibitor hypericin (HY) is high functionality in the dark, which has been shown to result in portfolio of anticancer activities both in vitro and in vivo. Here we show that treatment with HY significantly reduces growth rate of metastases in 2 murine models: breast adenocarcinoma (DA3) and squamous cell carcinoma (SQ2). Focus on metastases was achieved by resection of primary tumors at stages in which micrometastases exist in lungs. Long‐term animal survival in DA3 tumor‐excised groups increased from 15.6% in controls to 34.5% following supplementary treatment with HY. In mice bearing SQ2 tumor metastases, therapy with HY increased animal survival from 17.7% in controls to 46.1%. Using Laser‐induced fluorescence and multipixel spectral image analyses, we demonstrate that HY has a high tendency to accumulate in primary and metastatic tumors; HY content in lungs bearing metastases was approximately 2‐fold higher than in the lungs of healthy animals. The tendency of HY to preferentially concentrate in lung metastases, combined with its potent antiproliferative activities, may render HY as a useful supplementary modality in the treatment of metastatic cancer irrespective of photoactivation. © 2004 Wiley‐Liss, Inc.
Interleukin‐6 inhibits the growth of prostate cancer xenografts in mice by the process of neuroendocrine differentiation
Authors: Wang Qingcai , Horiatis Dimitris , Pinski Jacek
Published: May 2004

In vitro, the human prostate cancer (PCA) cell line LNCaP can be permanently transdifferentiated into a quiescent neuroendocrine (NE) phenotype by the cytokine interleukin‐6 (IL‐6). Recently, we have shown that the growth of prostate cancer cells is significantly suppressed when cocultured with NE cells. In order to explore the inhibitory activity of IL‐6 on prostate tumor growth, nude mice bearing xenografts of the PCA cell lines LNCaP and DU‐145 (a line that is incapable of NE transdifferentiation by IL‐6 in vitro) were treated with IL‐6 for 3 weeks, either injected around the tumor or systematically released from implanted minipumps. Both administration forms of IL‐6 inhibited the growth of LNCaP xenografts by more than 75% compared to the control group. In contrast, there was no difference in DU‐145 tumor growth between IL‐6‐treated animals and controls. In comparison to control and DU‐145 tumors, both IL‐6 injected and pump‐infused LNCaP tumors exhibited a significant increase in the expression of the NE markers neuron‐specific enolase (NSE) and βIII tubulin. Serum NSE levels were also significantly elevated in both IL‐6‐treated LNCaP tumor groups when compared to controls. IL‐6 treatment resulted in G0 cell cycle accumulation as evidenced by a loss of Ki‐67 expression in > 90% of LNCaP tumor cells. These combined results demonstrate that IL‐6‐induced NE transdifferentiation of PCA cells has a significant inhibitory effect on tumor growth in mice. Agents, like IL‐6, capable of NE transdifferentiation of PCA cells, should be considered as a new therapeutic approach for the treatment of prostate cancer. © 2004 Wiley‐Liss, Inc.
Role of α4 integrin and its ligand VCAM‐1 in the specific extravasation of a tumor‐specific TH2 clone into tumor tissue that initiates its rejection
Authors: Jin Zhe , Shen Yuan , Fujimoto Shigeyoshi
Published: May 2004

The effectiveness of anticancer immunotherapeutic strategies involving the transfer of tumor‐specific T cells depends on appropriate lymphocyte–endothelial cell interactions that facilitate the migration of lymphocytes into tumor. Here, we investigated the molecular mechanisms underlying the migration of the antigen‐specific Th2 CD4+ T‐cell clone YS1093 into S1509a tumor tissue. YS1093 is specific for the S1509a tumor but does not recognize the S713a tumor. Transfer of YS1093 cells into mice bearing both S1509a and S713a tumors caused only the S1509a tumor to regress. This regression was markedly inhibited by pretreating YS1093 cells with an anti‐α4 integrin MAb and administering an anti‐VCAM‐1 MAb at T‐cell transfer. Since vascular endothelial cells in S1509a tumor tissues express VCAM‐1 and the MHC class II (I‐Ek) molecule restricting YS1093 activity, labeled YS1093 cells migrated specifically into the S1509a tumor, and this migration was also blocked by the anti‐TCRβ F(ab′)2 and anti‐I‐Ek MAbs. Furthermore, in vitro assays revealed that anti‐CD3 MAb–mediated TCR cross‐linkage initiated the binding of α4 integrin on YS1093 cells to VCAM‐1. This adhesive activity was completely blocked by the anti‐α4 integrin MAb. These results strongly suggest that i.v.‐transferred YS1093 cells act in tumor regression by specifically recognizing their tumor antigen peptide in the context of I‐Ek on vascular endothelial cells in the S1509a tumor, which activates the binding of α4 integrin to VCAM‐1 on the endothelial cells, facilitating YS1093 extravasation into the tumor. It is likely that this initial migration of specific CD4+ T cells into tumor tissues promotes the subsequent infiltration into the tumor of other immunocytes that effect tumor destruction. © 2004 Wiley‐Liss, Inc.
Concise prediction models of anticancer efficacy of 8 drugs using expression data from 12 selected genes
Authors: Tanaka Tomotaka , Tanimoto Keiji , Otani Keiko , Satoh Kenichi , Ohtaki Megu , Yoshida Kazuhiro , Toge Tetsuya , Yahata Hiroshi , Tanaka Shinji , Chayama Kazuaki , Okazaki Yasushi , Hayashizaki Yoshihide , Hiyama Keiko , Nishiyama Masahiko
Published: May 2004

We developed concise, accurate prediction models of the in vitro activity for 8 anticancer drugs (5‐FU, CDDP, MMC, DOX, CPT‐11, SN‐38, TXL and TXT), along with individual clinical responses to 5‐FU using expression data of 12 genes. We first performed cDNA microarray analysis and MTT assay of 19 human cancer cell lines to sort out genes which were correlative in expression levels with cytotoxicities of the 8 drugs; we selected 13 genes with proven functional significance to drug sensitivity from a huge number of potent prediction marker genes. The correlation significance of each was confirmed using expression data quantified by real‐time RT‐PCR, and finally 12 genes (ABCB1, ABCG2, CYP2C8, CYP3A4, DPYD, GSTP1, MGMT, NQO1, POR, TOP2A, TUBB and TYMS) were selected as more reliable predictors of drug response. Using multiple regression analysis, we fixed 8 prediction formulae which embraced the variable expressions of the 12 genes and arranged them in order, to predict the efficacy of the drugs by referring to the value of Akaike's information criterion for each sample. These formulae appeared to accurately predict the in vitro efficacy of the drugs. For the first clinical application model, we fixed prediction formulae for individual clinical response to 5‐FU in the same way using 41 clinical samples obtained from 30 gastric cancer patients and found to be of predictive value in terms of survival, time to treatment failure and tumor growth. None of the 12 selected genes alone could predict such clinical responses. © 2004 Wiley‐Liss, Inc.
Omega‐3 fatty acids improve liver and pancreas function in postoperative cancer patients
Authors: Heller Axel R. , Rössel Thomas , Gottschlich Birgit , Tiebel Oliver , Menschikowski Mario , Litz Rainer J. , Zimmermann Thomas , Koch Thea
Published: May 2004

Epidemiologic studies have indicated that high intake of saturated fat and/or animal fat increases the risk of colon and breast cancer. Omega‐3 PUFAs in fish oil (FO) can inhibit the growth of human cancer cells in vitro and in vivo. These effects are related to the uptake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) into the cellular substrate pool and their competitive metabolism with arachidonic acid (AA) at the cyclooxygenase and 5‐lipoxygenase levels. The metabolites of EPA and DHA have less inflammatory and immunosuppressant potency than the substances derived from AA. Based on previous experimental data, we hypothesized that FO supplementation after major abdominal cancer surgery would improve hepatic and pancreatic function. Ours was a prospective, randomized, double‐blinded clinical trial on 44 patients undergoing elective major abdominal surgery, randomly assigned to receive total parenteral nutrition (TPN) supplemented with either soybean oil (SO 1.0 g/kg body weight daily, n = 20) for 5 days or a combination of FO and SO (FO 0.2 + SO 0.8 g/kg body weight daily, n = 24). Compared to pure SO supplementation in the postoperative period, FO significantly reduced ASAT [0.8 ± 0.1 vs. 0.5 ± 0.1 mmol/(l · sec)], ALAT [0.9 ± 0.1 vs. 0.6 ± 0.1 mmol/(l · sec)], bilirubin (16.1 ± 5.3 vs. 6.9 ± 0.6 mmol/l), LDH (7.7 ± 0.4 vs. 6.7 ± 0.4 mmol/(l · sec) and lipase (0.6 ± 0.1 vs. 0.4 ± 0.1 μmol/(l · sec) in the postoperative course. Moreover, patients with increased risk of sepsis (IL‐6/IL‐10 ratio >8) showed a tendency to shorter ICU stay (18 hr) under omega‐3 PUFA treatment. Weight loss as encountered after the SO emulsion of 1.1 ± 2.2 kg was absent in the FO group. After major abdominal tumor surgery, FO supplementation improved liver and pancreas function, which might have contributed to the faster recovery of patients. © 2004 Wiley‐Liss, Inc.
Synergistic effect of alcohol drinking and smoking on in vivo acetaldehyde concentration in saliva
Authors: Salaspuro Ville , Salaspuro Mikko
Published: May 2004

Alcohol drinking and smoking are independent risk factors for upper digestive tract cancers. Furthermore, their combined use interacts in a multiplicative way on cancer risk. There is convincing evidence that acetaldehyde, the first metabolite of ethanol and a constituent of tobacco smoke, is a local carcinogen in humans. Therefore, we examined the combined effect of alcohol drinking and tobacco smoking on in vivo acetaldehyde concentration in saliva. Seven smokers and 6 nonsmokers participated in the study. First, to measure the effect of alcohol on salivary acetaldehyde, all volunteers ingested 0.8 g/kg body weight of ethanol and saliva samples were collected every 20 min for 160 min thereafter. After a 3‐day washout period, smokers ingested again the same amount of ethanol and smoked one cigarette every 20 min and saliva samples were collected at 10 min intervals for 160 min. Acetaldehyde and ethanol concentrations were analyzed by headspace gas chromatograph. Firstly, smokers without concomitant smoking during ethanol challenge had 2 times higher in vivo salivary acetaldehyde concentrations than nonsmokers after ethanol ingestion (AUC 114.8 ± 11.5 vs. 54.2 ± 8.7 μM × hr, respectively; p = 0.002). Secondly, smokers with active smoking during ethanol challenge had 7 times higher in vivo salivary acetaldehyde levels than nonsmokers (AUC 369.5 ± 12.2 vs. 54.2 ± 8.7 μM × hr, respectively; p < 0.001). We conclude that this markedly increased exposure of upper digestive tract mucosa to carcinogenic salivary acetaldehyde of smoking and drinking subjects may explain the synergistic and multiplicative risk effect of alcohol drinking and tobacco smoking on upper gastrointestinal tract carcinogenesis. © 2004 Wiley‐Liss, Inc.
Peroxiredoxins, a novel protein family in lung cancer
Authors: Lehtonen Siri T. , Svensk Anne‐Mari , Soini Ylermi , Pääkkö Paavo , Hirvikoski Pasi , Kang Sang Won , Säily Marjaana , Kinnula Vuokko L.
Published: May 2004

Cigarette smoke, the major risk factor for lung cancer, induces an accumulation of reactive oxygen species. These have multiple effects on cell defense, cell proliferation and cell death. Thus, compounds involved in the regulators of redox balance can be hypothesized to play a fundamental role in both carcinogenesis and tumor progression. Here, we have evaluated the expressions of all 6 peroxiredoxins (Prxs I–VI) in lung carcinomas. Prxs represent a protein family with the capability of breaking down hydrogen peroxide; thus, they can participate in cellular antioxidant defense, regulate cell proliferation and increase drug resistance of cultured cells. Altogether 92 cases were investigated by immunohistochemistry, including 32 adenocarcinomas, 45 squamous cell, 9 small cell and 6 other carcinomas. Additionally, 11 cases with adenocarcinoma or squamous cell carcinoma were studied by Western analysis and/or by RT‐PCR. Prxs I, II, IV and VI were particularly elevated in lung carcinomas as assessed by immunohistochemistry and/or RT‐PCR. Western analysis revealed that Prxs I and IV were significantly elevated in tumors compared to nonmalignant tissue (p = 0.04 and 0.002, respectively). There were remarkable variations in Prx expression in various tumor subtypes, the most striking being Prx IV expression, which was mainly associated with adenocarcinoma. Elevated Prx VI expression was associated with high‐grade squamous cell carcinoma (p = 0.03) and Prx II expression, with advanced tumor stage (p = 0.01). Our results suggest that Prxs may have effects on the progression of lung cancer. © 2004 Wiley‐Liss, Inc.
Aberrant intracellular localization of SET‐CAN fusion protein, associated with a leukemia, disorganizes nuclear export
Authors: Saito Shoko , Miyaji‐Yamaguchi Mary , Nagata Kyosuke
Published: May 2004

The SET‐CAN fusion gene is the product of a chromosomal rearrangement found on 9q34 associated with an acute undifferentiated leukemia. SET‐CAN encodes an almost complete SET protein fused to the C‐terminal two‐thirds of CAN. SET is also known as TAF‐Iβ, a histone chaperone and intracellular inhibitor of protein phosphatase 2A, whereas CAN is identical to Nup214, a nucleoporin protein. To obtain insight into the leukemogenic function of SET/TAF‐Iβ‐CAN/Nup214, we have examined its subcellular localization. Immunofluorescence analyses showed that SET/TAF‐Iβ and CAN/Nup214 are found in the nucleus and the nuclear envelope, respectively, whereas the majority of SET/TAF‐Iβ‐CAN/Nup214 is localized in the nucleus. SET/TAF‐Iβ‐CAN/Nup214 interacted with hCRM1, one of the nuclear export factors, and caused aberrant intracellular localization of hCRM1. In cells expressing SET/TAF‐Iβ‐CAN/Nup214, a protein containing a nuclear export signal accumulated in the nucleus. The export of this protein was partially restored by overexpression of hCRM1. These results suggest that aberrantly localized molecules associated with SET/TAF‐Iβ‐CAN/Nup214 may be involved in oncogenesis. © 2004 Wiley‐Liss, Inc.
Combretastatin family member OXI4503 induces tumor vascular collapse through the induction of endothelial apoptosis
Authors: Sheng Yezhou , Hua Jianyi , Pinney Kevin G. , Garner Charles M. , Kane Robert R. , Prezioso Joseph A. , Chaplin David J. , Edvardsen Klaus
Published: May 2004

The mechanism of tumor cell killing by OXI4503 was investigated by studying vascular functional and morphological changes post drug administration. SCID mice bearing MHEC5‐T hemangioendothelioma were given a single dose of OXI4503 at 100 mg/kg. Tumor blood flow, measured by microsphere fluorescence, was reduced by 50% at 1 hr, and reached a maximum level 6–24 hr post drug treatment. Tumor vascular permeability, measured by Evan's blue and hemoglobin, increased significantly from 3 hr and peaked at 18 hr. The elevated tumor vessel permeability was accompanied by an increase in vascular endothelial growth factor (VEGF) from 1 hr post drug treatment. Immunohistochemical staining for CD31 and laminin showed that tumor blood vessels were affected as early as 3 hr but more prominent from 6 hr. From 12 hr, the vessel structure was completely destroyed. Histopathological and double immunohistochemical staining showed morphological change and induction of apoptosis in endothelial cells at 1–3 hr, followed by tumor cell necrosis from 6–72 hr. There were no statistically significant changes of Evan's blue and hemoglobin contents in liver tissue over the time course. These results suggest that OXI4503 selectively targets tumor blood vessels, and induces blood flow shutdown while it enhances tumor blood vessel permeability. The early induction of endothelial cell apoptosis leads to functional changes of tumor blood vessels and finally to the collapse of tumor vasculature, resulting in massive tumor cell necrosis. The time course of the tumor vascular response observed with OXI4503 treatment supports this drug for development as a stand alone therapy, and also lends support for the use of the drug in combination with other cancer therapies. © 2004 Wiley‐Liss, Inc.
Effect of exposure to light‐at‐night on life span and spontaneous carcinogenesis in female CBA mice
Authors: Anisimov Vladimir N. , Baturin Dmitri A. , Popovich Irina G. , Zabezhinski Mark A. , Manton Kenneth G. , Semenchenko Anna V. , Yashin Anatoly I.
Published: May 2004

The effect of constant illumination on the development of spontaneous tumors in female CBA mice was investigated. Fifty female CBA mice starting from the age of 2 months were kept under standard light/dark regimen (12 hr light:12hr dark; LD) and 50 CBA mice of similar age were kept under constant illumination (24 hr a day, 2,500 Lux, LL). Exposure to the LL regimen decreased food consumption but did not influence body weight, significantly accelerated age‐related disturbances in estrous function, and was followed by a significant increase in spontaneous tumor incidence in female CBA mice. Tumor incidence as well as the number of total or malignant tumors was significantly increased in the LL group compared to the LD group (p < 0.001). The incidence of lung adenocarcinomas, leukemias and hepatocarcinomas was 7/50; 6/50 and 4/50 in the LL group and 1/50; 0/50 and 0/50 in the LD group. Mice from the LL groups had shorter life spans then those from the LD group. The data demonstrate, for the first time, that exposure to constant illumination was followed by increases in the incidence of spontaneous lung carcinoma, leukemias and hepatocarcinoma in female CBA mice. © 2004 Wiley‐Liss, Inc.
CHEK2 variant I157T may be associated with increased breast cancer risk
Authors: Kilpivaara Outi , Vahteristo Pia , Falck Jacob , Syrjäkoski Kirsi , Eerola Hannaleena , Easton Douglas , Bartkova Jirina , Lukas Jiri , Heikkilä Päivi , Aittomäki Kristiina , Holli Kaija , Blomqvist Carl , Kallioniemi Olli‐Pekka , Bartek Jiri , Nevanlinna Heli
Published: May 2004

Cell cycle checkpoint kinase 2 (CHEK2) is a transducer of cellular responses to DNA damage. The CHEK2 1100delC has previously been shown to be a low‐penetrance breast cancer susceptibility allele. We have evaluated the role of another CHEK2 variant, I157T in the FHA domain of the gene, for association with breast cancer. I157T was found at a significantly higher frequency in the population‐based series of breast cancer patients (77/1035, 7.4%, odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.06–1.95, p = 0.021) than among population controls (100/1885, 5.3%). The frequency in the familial breast cancer patients was not elevated (28/507, 5.5%, OR = 1.04, 95% CI = 0.68–1.61). The I157T protein, that undermines cellular responses to ionizing radiation and shows deficiency in substrate recognition in vivo, was expressed at normal level in tumor tissues as well as in cultured cells. The I157T protein was stable and it dimerized with the wild‐type CHEK2 co‐expressed in human cells. These functional properties of the I157T protein suggest that this variant may have negative effect on the pool of normal CHEK2 protein in heterozygous carrier cells by formation of heterodimers with wild‐type CHEK2. The I157T variant may be associated with breast cancer risk, but the risk is lower than for 1100delC. © 2004 Wiley‐Liss, Inc.