bluuebunny/crossref_metadata_2025 huggingface dataset:
Asymmetric Induction and Configurational Stability at the Metal Centre in Half‐Sandwich (η6‐p‐Cymene)ruthenium(II) and (η5‐C5Me5)rhodium(III) Complexes Containing Chiral N‐N* Ligands with Different Rigidity and Flexibility
Authors: Saporita Maria , Bottari Giovanni , Brancatelli Giovanna , Drommi Dario , Bruno Giuseppe , Faraone Felice
Published: October 2007

The half‐sandwich chelate complexes [Ru(η6‐p‐cymene)(N‐N*)Cl]X (X = Cl, PF6) and [Rh(η5‐C5Me5)(N‐N*)Cl]X (X = SbF6, PF6; N‐N* = (Sa)‐1 and (Sa)‐2] have been prepared by treating the complexes [{Ru(η6‐p‐cymene)Cl2}2] and [{Rh(η5‐C5Me5)Cl2}2] with the bidentate N‐N* chiral ligands in their enantiomerically pure form. The ligands contain rigid 2‐pyridinyl or 8‐quinolinyl skeletons and the C2‐symmetric chiral framework trans‐2,5‐dimethylpyrrolidinyl or (+)‐(S)‐2,2′‐(2‐azapropane‐1,3‐diyl)‐1,1′‐binaphthalene. The chelate complexes [Ru(η6‐p‐cymene)(N‐N*)Cl]Cl and [Rh(η5‐C5Me5)(N‐N*)Cl]SbF6 [N‐N* = (Sa)‐1 and (Sa)‐2] were obtained in CH3OH or CHCl3, with 100 % diastereomeric excess, in the absolute configurations (Sa,SRu) and (Sa,RRh), respectively; the ligands (R,R)‐3 and (R,R)‐4 gave the corresponding products as pairs of diastereomers with high de. A kinetic effect is present during the formation of the ruthenium and rhodium chelate complexes. The (Sa,RRh) absolute configuration of [Rh(η5‐C5Me5)(N‐N*)Cl]PF6 [N‐N* = (Sa)‐1 and (Sa)‐2], which were obtained as a single diastereomer, was assigned by X‐ray diffraction determination of their molecular structures. The nucleophilic substitution reaction of chloride by iodide in [Ru(η6‐p‐cymene)(N‐N*)Cl]PF6 [N‐N* = (Sa)‐1 and (Sa)‐2], in methanol at 328 K, occurs with retention of configuration at the metal centre, and a possible mechanism is proposed on the basis of kinetic measurements. The results indicate a striking analogy between the isoelectronic complexes [Ru(η6‐p‐cymene)(N‐N*)Cl]PF6 and [Rh(η5‐C5Me5)(N‐N*)Cl]SbF6 containing the same N‐N* chiral ligand. A rationalisation of the results is proposed on the basis of X‐ray diffraction analysis and density functional calculations. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Coordination Polymers Constructed from [Mn(N)(CN)4]2–: Synthesis, Structures, and Magnetic Properties
Authors: Guo Jun‐Fang , Yeung Wai‐Fun , Gao Song , Lee Gene‐Hsiang , Peng Shie‐Ming , Lam Michael Hon‐Wah , Lau Tai‐Chu
Published: October 2007

The dimetallic complexes [{Ni(cyclen)}{Mn(N)(CN)4}·CH3OH]n (cyclen = 1,4,7,10‐tetraazacyclododecane) (1), [{Cu(cyclen)}{Mn(N)(CN)4}]n (2), and [{Mn(5,5′‐Me2salen)}2{Mn(N)(CN)4}·CH3OH]n [5,5′‐Me2salen = N,N′‐bis(5,5′‐dimethylsalicylidene)‐o‐ethylenediimine] (3) have been synthesized and structurally characterized. Compounds 1 and 2 have one‐dimensional chain structures, while compound 3 has a two‐dimensional sheet‐like network structure. Magnetic studies of 1 and 3 show that there is no significant magnetic coupling between the paramagnetic metal centers. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Click Chelators for Platinum‐Based Anticancer Drugs
Authors: Maisonial Aurélie , Serafin Patrycja , Traïkia Mounir , Debiton Eric , Théry Vincent , Aitken David J. , Lemoine Pascale , Viossat Bernard , Gautier Arnaud
Published: October 2007

Triazoles from “click chemistry” are convenient ligands for the formation of platinum complexes bearing combined triazole–amine or triazole–carboxylate moieties. Striking differences in the chelation modes are observed between the two series. One of the triazole–amine platinum complexes exhibits selective cytotoxicity against breast cancer cells lines. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
pH‐Induced Luminescence Changes of Chromophore‐Quencher Tricarbonylpolypyridylrhenium(I) Complexes with 4‐Pyridinealdazine
Authors: Cattaneo Mauricio , Fagalde Florencia , Katz Néstor E. , Borsarelli Claudio D. , Parella Teodor
Published: October 2007

The new chromophore‐quencher tricarbonylrhenium(I) complexes [Re(4,4′‐X2‐bpy)(CO)3(PCA)]+, [(4,4′‐X2‐bpy)(CO)3Re(μ‐PCA)Re(CO)3(4,4′‐X2‐bpy)]2+, and [(4,4′‐X2‐bpy)(CO)3ReI(μ‐PCA)RuII(NH3)5]3+ (X = Ph or CO2Me and PCA = 4‐pyridinealdazine) have been synthesized as their PF6– salts and characterized by spectroscopic, electrochemical, and photophysical techniques. In contrast to previously reported species with X = Me or H, these complexes emit at room temperature in CH3CN. The recovery of luminescence can thus be ascribed to the change of energy levels induced by adding electron‐withdrawing substituents to the 2,2′‐bipyridine ring, since the emissive ReII(X2bpy–) excited state becomes much lower in energy than the ReII(PCA–) non‐emissive excited state. For the mononuclear and symmetric dinuclear rhenium(I) complexes with X = CO2Me, consecutive protonation of both the pyridinyl and imine N atoms of PCA in aqueous solution leads to unusual bell‐shaped curves for both the absorption and the emission intensities vs. pH because of opposite effects on the electronic delocalization of PCA. This latter property can be employed to devise novel luminescent pH sensors of the on‐off‐on type. The corresponding unsymmetrical dinuclear complexes [(4,4′‐X2‐bpy)(CO)3ReI(μ‐PCA)RuIII(NH3)5]4+ have been obtained in situ by oxidizing the [ReI,RuII] precursors in CH3CN solution. Spectral and electrochemical measurements with these complexes lead to the values of the metal‐to‐metal electronic coupling elements.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Syntheses, Crystal Structures, and Optical Properties of Metal Complexes with 4′,5′‐Diaza‐9′‐(4,5‐disubstituted‐1,3‐dithiol‐2‐ylidene)fluorene Ligands
Authors: Zhu Qin‐Yu , Lu Wen , Zhang Yong , Bian Guo‐Qing , Gu Jing , Lin Xiao‐Min , Dai Jie
Published: October 2007

Four complexes with 4′,5′‐diaza‐9′‐[4,5‐bis(methylthio)‐1,3‐dithiol‐2‐ylidene]fluorene (L1) or 4′,5′‐diaza‐9′‐[4,5‐bis(ethylthio)‐1,3‐dithiol‐2‐ylidene]fluorene (L2) were synthesized. The complexes [Co(L1)2Cl2]·2CH3OH (1), [Cu(L2)2Cl2]·CH3OH·0.5CH2Cl2 (3), and [Cu(L2)2Br2]·CH3OH (4) adopt a trans configuration and the compound [Cd(L1)2(NO3)2] (2) is a cis structure. Short S···S, C···C, and C···S contacts were found to be important in the molecular packing. Both the solution and solid‐state electronic spectra show a redshift in the intramolecular CT bands when forming metal complexes. This intramolecular charge transition in the solid state is enhanced relative to that in solution. Their third‐order nonlinear optical properties of compounds 1–4 were studied, and the results reveal that these complexes exhibit negative γ values (about 10–30) and are self‐defocusing samples. These γ values are comparable to those of the known cluster compounds. The trans coordination of the two ligands to the metal center would be beneficial to the NLO properties. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
A Pyridine‐Stabilized Alumoxane Containing Two 1,3,2‐Diazaalumina[3]ferrocenophane Units
Authors: Wrackmeyer Bernd , Klimkina Elena V. , Milius Wolfgang
Published: October 2007

Dialuminoxane 6, in which both aluminum atoms are coordinated by pyridine and each is part of a 1,3‐bis(trimethylsilyl)‐1,3,2‐diazaalumina[3]ferrocenophane unit, was isolated as a side product accompanying the synthesis of the corresponding [3]ferrocenophane with Al–H or Al–Cl functionalities. Although attempted high‐yield syntheses of 6 failed, its structure could be established by 1H, 13C, and 29Si NMR spectroscopy in solution and by X‐ray structural analysis in the solid state. In various experiments to obtain 6, crystalline material was isolated and identified as the desired dialuminoxane either with a linear Al–O–Al (6A) or bent Al–O–Al (6B) unit. This is the first example of a structurally characterized bis(amino)dialuminoxane.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Antioxidant and antimutagenic effects of the crude foliar extract and the alkaloid brachycerine of Psychotria brachyceras
Authors: do Nascimento Naíla Cannes , Fragoso Variluska , Moura Dinara Jaqueline , e Silva Ana Catarina Romano , Fett‐Neto Arthur Germano , Saffi Jenifer
Published: October 2007

The monoterpene indole alkaloid brachycerine from Psychotria brachyceras has been shown to be induced by UV and to have in vitro antioxidant activity, indicating a possible protective role against the secondary effects of this radiation. In this work, we have studied the antioxidant properties of brachycerine and a crude foliar extract from P. brachyceras by using Saccharomyces cerevisiae strains proficient and deficient in antioxidant defenses. The mutagenic and antimutagenic potential of these substances were assayed in S.cerevisiae N123 strain in the presence and absence of H2O2. In addition, we tested the antioxidant capacity of brachycerine and a crude foliar extract from P. brachyceras on hydroxyl radicals (OH•) using the hypoxanthine/xanthine oxidase assay. The results show that brachycerine and the crude foliar extract of P. brachyceras have antioxidant and antimutagenic effects in yeast and probably this action is mainly due to the scavenging of OH• radicals. Environ. Mol. Mutagen., 2007. © 2007 Wiley‐Liss, Inc.
Difficulty of mode of action determination for trichloroethylene: An example of complex interactions of metabolites and other chemical exposures
Authors: Caldwell Jane C. , Keshava Nagalakshmi , Evans Marina V.
Published: October 2007

The mode(s) of action (MOA) of a pollutant for adverse health effects may be dependent on the mixture of metabolites resulting from exposure to a single agent and may also be affected by coexposure to pollutants that have similar targets or affected pathways. Trichloroethylene (TCE) can be an useful example for illustration of the complexity coexposure can present to elucidation of the MOA of an agent. TCE exposure has been associated with increased risk of liver and kidney cancer in both laboratory animal and epidemiologic studies. There are a number of TCE metabolites that could play a role in the induction of these effects. Coexposures of other chemicals with TCE typically occurs as a result of environmental cocontamination that include its own metabolites, such as trichloroacetic acid, dichloroacetic acid, and other pollutants with similar metabolites such as perchloroethylene. Behaviors such as alcohol consumption can also potentially modify TCE toxicity through similar MOAs. The U.S. Environmental Protection Agency (EPA)'s 2001 draft TCE risk assessment, Trichloroethylene (TCE) Health Risk Assessment: Synthesis and Characterization, concluded that it was difficult to determine which of the metabolites of TCE may be responsible for these effects, what key events in their hypothesized MOAs are involved, and the relevance of some of the hypothesized MOAs to humans. Since the publication of U.S. EPA's draft TCE assessment, several studies have been conducted to understand the effects of coexposures to TCE. They cover both pharmacodynamic and pharmacokinetic considerations. This article highlights some of the recently published scientific literature on toxicological interactions between TCE, its metabolites, and other coexposures, including solvents, haloacetates, and ethanol. These studies give insight into both the potential MOAs of TCE exposure itself and putative modulators of TCE toxicity, and illustrate the difficulties encountered in determining the MOAs and modulators of toxicity for pollutants with such complex metabolism and coexposures. Environ. Mol. Mutagen., 2007. Published 2007 Wiley‐Liss, Inc.
Evaluation of DNA damage induced by decabromodiphenyl ether (BDE‐209) in hemocytes of Dreissena polymorpha using the comet and micronucleus assays
Authors: Riva Consuelo , Binelli Andrea , Cogni Daniele , Provini Alfredo
Published: October 2007

The recent widespread production and use of flame retardants, polybrominated diphenyl ethers (PBDEs), is one of the reason of the increasing contamination observed worldwide. At the present, deca‐BDE mixture, in which the decabromodiphenyl ether (BDE‐209) is the major congener (98%), dominates the EU market. The potential genotoxicity of BDE‐209 was examined in the freshwater bivalve zebra mussel (Dreissena polymorpha) by means of Comet assay and micronucleus assay (MN assay). Mussels were exposed in vivo to BDE‐209 at nominal concentration of 0.1, 2, and 10 μg/l under laboratory conditions. The assays were performed on the bivalve hemocytes monitoring the levels of DNA strand breaks and the percentage of micronuclei until 168 and 96 hr of exposure, respectively. At the same time, BDE‐209 levels were measured daily in mussel soft tissues to evaluate the bioaccumulation. Results of the Comet assay showed a significant increase of DNA damages compared to controls, but a lack of dose/effect relationship probably due to the formation of less‐brominated congeners. By contrast, no significant changes in MN frequency from baseline levels were observed. These preliminary results about the potential genotoxicity of this compound in invertebrates indicated a clear BDE‐209 capability to induce DNA damage, but no irreversible effects on DNA hemocytes. Furthermore, bioaccumulation of this high‐molecular‐weight substance and its uptake mechanism in zebra mussel are also discussed. Environ. Mol. Mutagen., 2007. © 2007 Wiley‐Liss, Inc.
An exact expression for MPSK SEP
Authors: Nadarajah Saralees
Published: October 2007

Many of the known expressions for the M ary phase shift keying (MPSK) symbol error probability (SEP) are of dubious nature because they are based on an infinite series representation that diverges. In this note, an exact and convergent expression is derived for the MPSK SEP. Some numerical comparison is provided with the known expressions. Copyright © 2007 John Wiley & Sons, Ltd.
Arylamine N‐acetyltransferase 1 expression in breast cancer cell lines: A potential marker in estrogen receptor‐positive tumors
Authors: Wakefield Larissa , Robinson James , Long Hilary , Ibbitt J. Claire , Cooke Susanna , Hurst Helen C. , Sim Edith
Published: October 2007

The prognosis for patients with estrogen receptor (ER)‐positive breast cancer has improved significantly with the prescription of selective ER modulators (SERMs) for ER‐positive breast cancer treatment. However, only a proportion of ER‐positive tumors respond to SERMs, and resistance to hormonal therapies is still a major problem. Detailed analysis of published microarray studies revealed a positive correlation between overexpression of the drug metabolizing enzyme arylamine N‐acetyltransferase type 1 (NAT1) and ER positivity, and increasing evidence supports a biological role for NAT1 in breast cancer progression. We have tested a range of ER‐positive and ER‐negative breast cancer cell lines for NAT1 enzyme activity, and monitored promoter and polyadenylation site usage. Amongst ER‐positive lines, NAT1 activities ranged from 202 ± 28 nmol/min/mg cellular protein (ZR‐75‐1) to 1.8 ± 0.4 nmol/min/mg cellular protein (MCF‐7). The highest levels of NAT1 activity could not be attributed to increased NAT1 gene copy number; however, we did detect differences in NAT1 promoter and polyadenylation site usage amongst the breast tumor‐derived lines. Thus, whilst all cell lines tested accumulated transcripts derived from the proximal promoter, the line expressing NAT1 most highly additionally initiated transcripts initiating at a more distal, “tissue”‐specific promoter. These data pave the way for investigating NAT1 transcripts as candidate prognostic markers in ER‐positive breast cancer. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045‐2257/suppmat. © 2007 Wiley‐Liss, Inc.
Model for end-stage liver disease score and systemic inflammatory response are major prognostic factors in patients with cirrhosis and acute functional renal failure
Authors: Thabut Dominique , Massard Julien , Gangloff Alice , Carbonell Nicolas , Francoz Claire , Nguyen-Khac Eric , Duhamel Christian , Lebrec Didier , Poynard Thierry , Moreau Richard
Published: October 2007

Although it is often functional at presentation, acute renal failure has a poor prognosis in patients with cirrhosis. The role of inflammation, a key event in the outcome of cirrhosis, has never been studied in this setting. We aimed to investigate the predictive factors of mortality in patients with cirrhosis and acute functional renal failure, specifically in relation to inflammatory events. One hundred consecutive patients with cirrhosis from 5 French hospitals were prospectively included at the day of onset of acute renal failure. Medical history, treatments, and procedures during the month before inclusion were recorded. Physical examination, blood and urinary chemistries, and renal ultrasound examination were performed. The presence of systemic inflammatory response syndrome (SIRS), infection, and sepsis was assessed. The primary outcome was in-hospital mortality. The mechanism of renal failure was functional in 83 patients. Causes of renal failure were hypovolemia (34%), hepatorenal syndrome without ongoing infection (17%), hepatorenal syndrome with ongoing infection (16%), nephrotoxicity (2%), and multifactorial (31%). SIRS was observed in 41% of patients, 56% of them with infection. In-hospital mortality was 68% in patients with SIRS and 33% in patients without (

P

= 0.001). In multivariate analysis, only model for end-stage liver disease score and presence of SIRS, but not infection, remained associated with a poor outcome.

Conclusion:

The presence of SIRS, with or without infection, is a major independent prognostic factor in patients with cirrhosis and acute functional renal failure. This suggests that preventing and treating SIRS could decrease mortality in patients with cirrhosis and acute renal failure. (Hepatology 2007.)
Efficacy of selegiline add on therapy to risperidone in the treatment of the negative symptoms of schizophrenia: a double‐blind randomized placebo‐controlled study
Authors: Amiri Afshar , Noorbala Ahmad‐Ali , Nejatisafa Ali‐Akbar , Ghoreishi Abolfazl , Derakhshan Mohammad‐Kamran , Khodaie‐Ardakani Mohammad‐Reza , Hajiazim Mohammad , Raznahan Maedeh , Akhondzadeh Shahin
Published: October 2007

Objective

It has been reported that selegiline, a Selective Monoamine Oxidase Inhibitor B (MAOI‐B), at low doses would be helpful for treating negative symptoms in schizophrenia. Nevertheless, the results are contradictory so far. This study was designed to investigate the effect of selegiline added to risperidone as augmentation therapy in patients with chronic schizophrenia and prominent negative symptoms in an 8 week, double blind and randomized clinical trial.

Methods

Eligible participants in this study were 40 patients with chronic schizophrenia. All patients were inpatients and were in the active phase of the illness, and met DSM‐IV‐TR criteria for schizophrenia. Patients were allocated in a random fashion, 20 to risperidone 6 mg/day plus selegiline 10 mg/day (5 mg bid) and 20 to risperidone 6 mg/day plus placebo. The principal measure of the outcome was Positive and Negative Syndrome Scale (PANSS).

Results

Although both protocols significantly decreased the score of the positive, negative, and general psychopathological symptoms over the trial period, the combination of risperidone and selegiline showed a significant superiority over risperidone alone in decreasing negative symptoms and PANSS total scores.

Conclusion

The present study indicates selegiline as a potential adjunctive treatment strategy for the negative symptoms of schizophrenia. Nevertheless, results of larger controlled trials are needed before recommendation for a broad clinical application can be made. Copyright © 2007 John Wiley & Sons, Ltd.
Ultrasonic measurement of suspended sediment concentrations: an experimental validation of the approach using kaolin suspensions and reservoir sediments under variable thermal conditions
Authors: Sung C. C. , Huang Y. J. , Lai J. S. , Hwang G. W.
Published: October 2007

Multiphase suspension systems are used extensively in hydrology, biochemistry, and the food industry. Ultrasonic spectroscopy is a rapid, on‐line, non‐invasive measurement technique for suspension characterization over different particle sizes and a wide range of concentration. Although the properties of kaolin suspensions have been investigated extensively, kaolin ultrasonic attenuation properties at different temperatures and concentrations have not yet been reported. Through experimental validation in the laboratory, this study provides results from a series of measurements of kaolin ultrasonic attenuation over a wide range of concentrations (0–300 000 ppm) and practical temperatures (5–25 °C). The ultrasonic measurement of attenuation of sediment sampled from the Shihmen reservoir in Taiwan is also investigated. Results show that variations in ultrasonic attenuation are driven by concentration and temperature. Two regression functions are established to quantitatively relate attenuation to kaolin concentration and the Shihmen reservoir sample at a given temperature. An ultrasonic system is designed and manufactured for real‐time sediment concentration monitoring in the Shihmen reservoir based on these experimental ultrasonic attenuation measurements. Copyright © 2007 John Wiley & Sons, Ltd.
Hereditary nonpolyposis colorectal cancer in endometrial cancer patients
Authors: Yoon Sang Nam , Ku Ja‐Lok , Shin Young‐Kyoung , Kim Kyung‐Hee , Choi Jin‐Sung , Jang Eun‐Ja , Park Hyoung‐Chul , Kim Duck‐Woo , Kim Min A. , Kim Woo Ho , Lee Taek Sang , Kim Jae Weon , Park Noh‐Hyun , Song Yong‐Sang , Kang Soon‐Beom , Lee Hyo‐Pyo , Jeong Seung‐Yong , Park Jae‐Gahb
Published: October 2007

Endometrial cancer is the second most common cancer in hereditary nonpolyposis colorectal cancer (HNPCC). It has often been overlooked to explore the possibility of HNPCC in endometrial cancer patients. Our study was to investigate how many HNPCC patients existed among endometrial cancer patients. Among patients who underwent hysterectomy for endometrial cancer at Seoul National University Hospital from 1996 to 2004, 113 patients were included, whose family history and clinical data could be obtained and tumor specimens were available for microsatellite instability (MSI) testing and immunohistochemical (IHC) staining of MLH1, MSH2 and MSH6 proteins. There were 4 (3.5%) clinical HNPCC patients fulfilling the Amsterdam criteria II, and 2 (2/4, 50%) of them carried MSH2 germline mutations. There were also 8 (7.1%) suspected HNPCC (s‐HNPCC) patients fulfilling the revised criteria for s‐HNPCC, and one (1/8, 12.5%) of them revealed MLH1 germline mutation. In 101 patients, who were not clinical HNPCC or s‐HNPCC, 11 patients showed both MSI‐high and loss of expression of MLH1, MSH2 or MSH6 proteins, and 2 (2/11, 18.2%) of them showed MSH6 germline mutations. In 113 patients with endometrial cancer, we could find 5 (4.4%) HNPCC patients with MMR germline mutation and 2 (1.8%) clinical HNPCC patients without identified MMR gene mutation. Family history was critical in detecting 3 HNPCC patients with MMR germline mutation, and MSI testing with IHC staining for MLH1, MSH2 and MSH6 proteins was needed in the diagnosis of 2 HNPCC patients who were not clinical HNPCC or s‐HNPCC, especially for MSH6 germline mutation. © 2007 Wiley‐Liss, Inc.
Synthesis and biological evaluation of an albumin‐binding prodrug of doxorubicin that is cleaved by prostate‐specific antigen (PSA) in a PSA‐positive orthotopic prostate carcinoma model (LNCaP)
Authors: Graeser Ralph , Chung Da‐Eun , Esser Norbert , Moor Sandra , Schächtele Christoph , Unger Clemens , Kratz Felix
Published: October 2007

The prostate‐specific antigen (PSA) is a serine protease that is over‐expressed in prostate carcinoma and represents a molecular target for selectively releasing an anticancer agent from a prodrug formulation. We have recently investigated a macromolecular prodrug strategy for improved cancer chemotherapy based on 2 features: (i) rapid and selective binding of thiol‐reactive prodrugs to the cysteine‐34 position of endogenous albumin after intravenous administration, and (ii) enzymatic release of the albumin‐bound drug at the tumor site (Mansour et al., Cancer Res 2003, 63, 4062–4066). In this work, we describe an albumin‐binding prodrug, EMC‐Arg‐Ser‐Ser‐Tyr‐Tyr—Ser‐Arg‐DOXO [EMC: ϵ‐Maleimidocaproic acid; DOXO = doxorubicin; X = amino acid] that is cleaved by PSA. Because of the incorporation of 2 arginine residues, the prodrug exhibited excellent water‐solubility and was rapidly and selectively bound to endogenous albumin. Incubation studies with PSA and tumor homogenates from PSA‐positive tumors (LNCaP) demonstrated that the albumin‐bound form of the prodrug was efficiently cleaved by PSA at the P1–P′ 1 scissile bond releasing the doxorubicin dipeptide H‐Ser‐Arg‐DOXO, which was further degraded to doxorubicin as the final cleavage product. In cell culture experiments, the prodrug was ∼100‐fold less active against LNCaP cells than the free drug. In contrast, in a mouse model of human prostate cancer using luciferase transduced LNCaP cells orthotopically implanted in SCID mice, the prodrug showed enhanced antitumor efficacy when compared to doxorubicin. Doxorubicin treatment at a dose of 2 × 4 mg/kg caused significant weight loss and mortality (−25%), and did not result in a significant antitumor response at the end of the experiment. The prodrug at 3 × 12 mg/kg doxorubicin equivalents, however, was well tolerated and induced a significant reduction in tumor size of 62% (±25%, **p = 0.003) as well as a decrease of the metastatic burden in the lungs as detected in luciferase assays (−50%, SD ± 115%, *p = 0.038). © 2007 Wiley‐Liss, Inc.
HER‐2 status discrepancy between primary breast cancer and metastatic sites. Impact on target therapy
Authors: Santinelli Alfredo , Pisa Eleonora , Stramazzotti Daniela , Fabris Guidalberto
Published: October 2007

In this prospective study, we determined HER‐2 status in primary breast invasive carcinomas and in the paired lymph node metastases (synchronous and metachronous), local recurrence and metachronous distant metastases, to verify the percentage of discordant cases. HercepTest™ and Fluorescence in situ hybridization (FISH) were used to determine HER‐2 status on 119 cases of primary infiltrating breast carcinoma and paired metastases (45 cases with synchronous lymph node metastases, 9 cases with metachronous lymph node metastases, 30 cases with local recurrence, and 35 cases with metachronous distant metastases). A therapeutically significant HER‐2 status discordance was demonstrated between primary carcinoma and synchronous lymph node metastases (6.7%), local recurrence (13.3%) and metachronous distant metastases (28.6%). In the first comparison, there was a normal HER‐2 status in primary tumours and HER‐2 amplification in paired metastases, in the second the opposite phenomenon was present, and both types of discordance were evident in the third comparison. Considering the cases of local recurrences and metachronous distant metastases all together, 14 out of 65 cases (21.5%) showed a therapeutically significant discordance of HER‐2 status between the primary tumour and the paired metachronous recurrence or metastasis (p < 0.001), the 15.4% of cases showing normal HER‐2 status in the primary tumour and HER‐2 amplification in the neoplastic relapse. For the treatment of metastatic patients, the evaluation of HER‐2 status should be performed in neoplastic tissue from metastatic site, whenever possible. This procedure could be also suggested in the patients that are metastatic at the time of diagnosis. © 2007 Wiley‐Liss, Inc.
Risk of gastroesophageal cancer among smokers and users of Scandinavian moist snuff
Authors: Zendehdel Kazem , Nyrén Olof , Luo Juhua , Dickman Paul W. , Boffetta Paolo , Englund Anders , Ye Weimin
Published: October 2007

Although Scandinavian moist snuff (“snus”), no doubt, is a safer alternative to smoking, there is limited evidence against an association with gastroesophageal cancers. In a retrospective cohort study, we investigated esophageal and stomach cancer incidence among 336,381 male Swedish construction workers who provided information on tobacco smoking and snus habits within a health surveillance program between 1971 and 1993. Essentially complete follow‐up through 2004 was accomplished through linkage to several nationwide registers. Multivariable Cox proportional hazards regression models estimated relative risks (RR) and 95% confidence intervals (CIs). Compared to never‐users of any tobacco, smokers had increased risks for adenocarcinoma (RR = 2.3, 95% CI 1.4–3.7) and squamous cell carcinoma (RR = 5.2, 95% CI 3.1–8.6) of the esophagus, as well as cardia (RR = 2.1, 95% CI 1.5–3.0) and noncardia stomach (RR = 1.3, 95% CI 1.2–1.6) cancers. We also observed excess risks for esophageal squamous cell carcinoma (RR = 3.5, 95% CI 1.6–7.6) and noncardia stomach cancer (RR = 1.4, 95% CI 1.1–1.9) among snus users who had never smoked. Although confounding by unmeasured exposures, and some differential misclassification of smoking, might have inflated the associations, our study provides suggestive evidence for an independent carcinogenic effect of snus. © 2007 Wiley‐Liss, Inc.
Identification of 2 putative critical segments of 17q gain in neuroblastoma through integrative genomics
Authors: Vandesompele Jo , Michels Evi , De Preter Katleen , Menten Björn , Schramm Alexander , Eggert Angelika , Ambros Peter F. , Combaret Valerie , Francotte Nadine , Antonacci Francesca , De Paepe Anne , Laureys Geneviève , Speleman Frank , Van Roy Nadine
Published: October 2007

Partial gain of chromosome arm 17q is the most frequent genetic change in neuroblastoma (NB) and constitutes the strongest independent genetic factor for adverse prognosis. It is assumed that 1 or more genes on 17q contribute to NB pathogenesis by a gene dosage effect. In the present study, we applied chromosome 17 tiling path BAC arrays on a panel of 69 primary tumors and 28 NB cell lines in order to reduce the current smallest region of gain and facilitate identification of candidate dosage sensitive genes. In all tumors and cell lines with 17q gain, large distal segments were consistently present in extra copies and no interstitial gains were observed. In addition to these large regions of distal gain with breakpoints proximal to coordinate 44.3 Mb (17q21.32), smaller regions of gain (distal to coordinate 60 Mb at 17q24.1) were found superimposed on the larger region in a minority of cases. Positional gene enrichment analysis for 17q genes overexpressed in NB showed that dosage sensitive NB oncogenes are most likely located in the gained region immediately distal to the most distal breakpoint of the 2 breakpoint regions. Interestingly, comparison of gene expression profiles between primary tumors and normal fetal adrenal neuroblasts revealed 2 gene clusters on chromosome 17q that are overexpressed in NB, i.e. a region on 17q21.32 immediately distal to the most distal breakpoint (in cases with single regions of gain) and 17q24.1, a region coinciding with breakpoints leading to superimposed gain. © 2007 Wiley‐Liss, Inc.
Targeted photodynamic therapy with multiply‐loaded recombinant antibody fragments
Authors: Bhatti Manpreet , Yahioglu Gokhan , Milgrom Lionel R. , Garcia‐Maya Mitla , Chester Kerry A. , Deonarain Mahendra P.
Published: October 2007

Current photodynamic therapy (PDT) of cancer is limited by inefficiencies involved in specifically targeting photosensitizers to tumors. Although antibodies are being explored as targeting vehicles, they present significant challenges, particularly in terms of pharmacokinetics and drug‐coupling. We describe here a novel and effective system to covalently attach multiple photosensitizer molecules (both preclinical, pyropheophorbide‐a and clinically approved, verteporfin photosensitizers) to single‐chain Fvs. Further, we demonstrate that not only do the resulting photoimmunoconjugates retain photophysical functionality, they are more potent than either free photosensitizer, effectively killing tumor cells in vitro and in vivo. For example, treatment of human breast cancer xenografts with a photoimmunoconjugate comprising an anti‐HER‐2 scFv linked to 8–10 molecules of pyropheophorbide‐a leads to significant tumor regression. These results give an insight into the important features that make scFvs good carriers for PDT drugs and provide proof of concept of our unique approach to targeted photodynamic therapy (tPDT). This promises to significantly improve on current photodynamic therapies for the treatment of cancer. © 2007 Wiley‐Liss, Inc.
RBP2‐H1/JARID1B is a transcriptional regulator with a tumor suppressive potential in melanoma cells
Authors: Roesch Alexander , Mueller Andrea M. , Stempfl Thomas , Moehle Christoph , Landthaler Michael , Vogt Thomas
Published: October 2007

The RBP2‐H1/JARID1B nuclear protein belongs to the ARID family of DNA‐binding proteins and is a potential tumor suppressor that is lost during melanoma development. As we have recently shown, one physiological function of RBP2‐H1/JARID1B is to exert cell cycle control via maintenance of active retinoblastoma protein. We now add new evidence that RBP2‐H1/JARID1B can also directly regulate gene transcription in a reporter assay system, either alone or as part of a multimolecular complex together with the developmental transcription factors FOXG1b and PAX9. In melanoma cells, chromatin immunoprecipitation combined with promoter chip analysis (ChIP‐on‐chip) suggests a direct binding of re‐expressed RBP2‐H1/JARID1B to a multitude of human regulatory chromosomal elements (promoters, enhancers and introns). Among those, a set of 23 genes, including the melanoma relevant genes CDK6 and JAG‐1 could be confirmed by cDNA microarray analyses to be differentially expressed after RBP2‐H1/JARID1B re‐expression. In contrast, in nonmelanoma HEK 293 cells, RBP2‐H1/JARID1B overexpression only evokes a minor transcriptional response in cDNA microarray analyses. Because the transcriptional regulation in melanoma cells is accompanied by an inhibition of proliferation, an increase in caspase activity and a partial cell cycle arrest in G1/0, our data support an anti‐tumorigenic role of RBP2‐H1/JARID1B in melanocytic cells. © 2007 Wiley‐Liss, Inc.
Family history of breast or ovarian cancer modifies the risk of secondary leukemia after breast cancer: Results from a population‐based study
Authors: Verkooijen Helena M. , Fioretta Gerald , Rapiti Elisabetta , Vlastos Georges , Neyroud‐Caspar Isabelle , Chappuis Pierre O. , Bouchardy Christine
Published: October 2007

We evaluated the impact of a family history of breast/ovarian cancer on the risk of secondary leukemia following breast cancer. At the Geneva cancer registry, we identified 4,397 patients diagnosed with invasive breast cancer between 1990 and 2004. Patients were followed up for leukemia until the end of 2005. Family history was categorized as positive in patients with ≥1 first‐ or second‐degree relative with breast/ovarian cancer. We compared leukemia rates in patients with positive and negative family histories with those expected in the general population, generating standardized incidence ratios (SIRs). With Cox regression analysis, we calculated adjusted risks of secondary leukemia in patients with familial risks compared to those without it. Breast cancer patients had a significantly increased risk of secondary acute leukemia (SIR 3.2, 95% CI: 1.2–6.9) but not of chronic leukemia (SIR 1.6, 95% CI: 0.6–3.5). Among patients with a positive family history (n = 1.125, 25.6%), the SIRs were 5.7 (95% CI: 1.2–16.6) for acute and 5.2 (95% CI: 1.4–13.3) for chronic leukemia. Among breast cancer patients, family history was independently associated with leukemia [adjusted hazard ratio (HRadj) of 3.2, 95% CI: 1.1–9.2, among patient with vs. without family history]. The effect of family history was stronger for chronic leukemia (HRadj: 11.6, 95% CI 1.3–104.7) than for acute leukemia (HRadj 1.6, 95% CI: 0.4–6.6). Breast cancer patients with a family history of breast/ovarian have an increased risk of secondary leukemia, both compared to the general population as well as to breast cancer patients without family histories. This excess risk is largely due to the increased risk of secondary chronic leukemia. © 2007 Wiley‐Liss, Inc.
Expression of αCP‐4 inhibits cell cycle progression and suppresses tumorigenicity of lung cancer cells
Authors: Castaño Zafira , Vergara‐Irigaray Nuria , Pajares Maria J. , Montuenga Luis M. , Pio Ruben
Published: October 2007

The protein αCP‐4 (also known as hnRNP E4) is an RNA binding protein encoded by a gene at 3p21, one of the most common altered regions in lung cancer. It has been proposed that αCP‐4 may function as a lung tumor suppressor. Lack of αCP‐4 expression is frequent in highly proliferative lung tumors and correlates with αCP‐4 allele losses. The aim of this study was to evaluate the effect of αCP‐4 on the tumorigenic capacity of lung cancer cells. αCP‐4 expression was induced by transient transfection or stable infection with recombinant retroviruses. Induction of αCP‐4 expression caused cell cycle arrest in G2/M in 3 out of the 7 lung cancer cell lines studied, while no effect on apoptosis was observed. Anchorage‐independent growth and invasion capacity of H1299 cells were significantly reduced by αCP‐4 induction. Tumorigenicity of H1299 cells in nude mice was greatly inhibited by the expression of αCP‐4. Moreover, induction of αCP‐4 expression in already established tumors resulted in a sudden growth arrest. Immunocytochemistry analysis of the xenograft tumors revealed an in vivo effect of αCP‐4 on cell proliferation and no effect on apoptosis. Finally, αCP‐4 showed a subcellular localization different from αCP‐4a, a splice variant that does not affect cell proliferation. In conclusion, expression of αCP‐4 can inhibit proliferation and tumorigenesis of lung cancer cells, both in vivo and in vitro, by delaying the progression of the cell cycle. © 2007 Wiley‐Liss, Inc.
Recent advances in strategies for immunotherapy of human papillomavirus‐induced lesions
Authors: Kanodia Shreya , Da Silva Diane M. , Kast W. Martin
Published: October 2007

Human papillomavirus (HPV)‐induced lesions are distinct in that they have targetable foreign antigens, the expression of which is necessary to maintain the cancerous phenotype. Hence, they pose as a very attractive target for “proof of concept” studies in the development of therapeutic vaccines. This review will focus on the most recent clinical trials for the immunotherapy of mucosal and cutaneous HPV‐induced lesions as well as emerging therapeutic strategies that have been tested in preclinical models for HPV‐induced lesions. Progress in peptide‐based vaccines, DNA‐based vaccines, viral/bacterial vector‐based vaccines, immune response modifiers, photodynamic therapy and T cell receptor based therapy for HPV will be discussed. © 2007 Wiley‐Liss, Inc.
Applying the Infant‐Toddler Social & Emotional Assessment (ITSEA) and Brief‐ITSEA in early intervention
Authors: Briggs‐Gowan Margaret J. , Carter Alice S.
Published: October 2007

To examine the internal consistency and validity of the Infant‐Toddler Social and Emotional Assessment (ITSEA) and Brief‐ITSEA (BITSEA) parent‐report questionnaires in an early intervention sample. A sociodemographically diverse sample of 192 parents of 11‐ to 36‐month‐old children referred to early intervention programs completed surveys containing the ITSEA, BITSEA, and Child Behavior Checklist (CBCL). Parents were interviewed with the Vineland Adaptive Behavior Scales. Evaluators blind to children's status on the ITSEA and BITSEA rated child behavior during developmental assessments. Finally, a subsample of 71 children was administered the Mullen Scales of Early Learning. Findings support the internal consistency of the ITSEA and BITSEA, with the majority of Cronbach's alphas above .70. Supporting validity, ITSEA and BITSEA problem scores correlated significantly with CBCL Internalizing and Externalizing scores (rs=.28 to .78), as well as with observational ratings of problem behaviors on constructs paralleling the ITSEA domains (rs=.21 to .45). In contrast, ITSEA Competence and BITSEA Competence demonstrated moderate negative associations with CBCL scores (rs=−.39 to −.43). Finally, ITSEA Competence and BITSEA Competence correlated significantly with developmental level on the Mullen, Vineland Socialization, and observational ratings of competence (rs=.25 to .43). Emphasizing the importance of addressing social‐emotional issues in early intervention settings, 58.6% of children had high social‐emotional/behavioral problems and/or low competence on the ITSEA; 39.8% had high ITSEA Problems and 38.5% had low ITSEA Competence. Results indicate the need to assess social‐emotional adjustment in early intervention settings and support the use of the ITSEA and BITSEA for this purpose.
With a little help from my friends?: Self‐regulation in groups of young children
Authors: Mccabe Lisa A. , Brooks‐Gunn Jeanne
Published: October 2007

This study examined self‐regulation in preschool children (mean age=51 months; 47% boys) using three situational assessments tapping delay of gratification and motor control. Assessments represented a novel adaptation for use with both individual (N=116) and groups (N=44) of four familiar peers in ecologically valid settings. Results suggest that preschoolers demonstrate an increasing ability to self‐regulate with age, as well as some evidence for girls performing better than boys on the Gift Wrap situational assessment. Children were less able to demonstrate self‐regulation in the peer group context as compared to individual assessments. Differences between age groups and gender were not significant when children were assessed with their peers. The influence of peers on self‐regulation behavior is a complex relationship with no clear patterns identified in this research. Implications for future research and assessment efforts are discussed.
Measures of effortful regulation for young children
Authors: Spinrad Tracy L. , Eisenberg Nancy , Gaertner Bridget M.
Published: October 2007

Emotion‐related regulation is a topic of increasing interest among researchers, yet there is little agreement on ways to measure emotion regulation in young children. In this paper, we first consider important conceptual distinctions in regard to the different types of emotion‐related regulation and control. Next, we describe a number of ways researchers have assessed children's regulation. We also present data from the Toddler Emotional Development project, in which laboratory‐based measures of effortful regulation were used. In this section, we highlight the measures that show promise (and those that did not work well). Future directions for research on the measurement of effortful regulation are presented
Conundrums in the use of observational measures of socioemotional behavior
Authors: Martin Mcdermott Jennifer N. , Fox Nathan A.
Published: October 2007

The potential for translation of observational measures of social and emotional behavior used in small‐scale studies for use in large‐, possibly national‐scale, studies of child development is currently an unresolved challenge. To begin to address this issue, the advantages and disadvantages to using observational measures of social and emotional behavior are discussed. In addition, alternatives to observational measures that may be helpful in assessing social and emotional behavior are considered with special emphasis on the benefits of cognitive measures.
Commentary: Difficulties assessing social and emotional behavior in large‐scale national studies
Authors: Fitzgerald Hiram E.
Published: October 2007

Innovations in the assessment of emotional development provide new opportunities to track behavioral undercontrol from early childhood to adolescence and adulthood. Less attention is given to the assessment and measurement of negative affect. Questionnaires used to measure emotions and emotion‐regulated behavior have strong psychometric properties. Large‐scale population studies provide challenges for large assessment batteries and place great pressure for the use of short forms, but it is not always clear that short forms share the psychometrics strengths of their longer versions. Use of narratives provides opportunities to gain deeper insights into the child's experiential world. Overall, the diverse set of measurement tools that has been developed to assess emotion‐regulated behavior during the earliest years contributes to our ability to design effective prevention programs or intervention strategies to shift developmental pathways.
Hydrologic and economic evaluation of water‐saving options in irrigation systems
Authors: Khan S. , Abbas A. , Gabriel H. F. , Rana T. , Robinson D.
Published: October 2007

This paper investigates a range of water savings options at irrigation system level and ranks these options according to the potential savings of each option and the economic return in terms of water saved (ML – megalitres) for each dollar invested. Most of the work was conducted on large‐area farms of the Murrumbidgee Irrigation Area (MIA) and Coleambally Irrigation Area (CIA) in the Murrumbidgee River catchment, New South Wales, Australia. Field‐based on‐farm water savings for scenarios analysed ranged from 0.1 ML ha−1 up to 3.9 ML ha−1 (10–390 mm). As capital can be a limiting resource to farmers, options that have the lowest cost per ML saved may be more appealing than options that have a higher cost but may also have higher net benefits over time. The water savings that derived the highest net benefit per megalitre saved were conversion to drip and subsurface drip for the case study farms and laser levelling which had net benefits ranging from A$ 1 64 to A$ 344 ML−1 saved per year. All of the other options had net benefits ranging from A$ 4 to A$ 37 ML−1 saved per year. All of the options that had a low annualised cost also had a relatively low net benefit (less than A$ 24 ML−1 saved per year). Marginal costs of off‐farm water savings increase with the volume of water saved. In the MIA up to 20 GL (1 gigalitre = 1 MCM million cubic metres) of potential water savings are possible at a marginal capital cost of around A$ 1500–2000 ML−1. Marginal capital costs then rise rapidly, reaching A$ 4000 ML−1 at around 38 GL reflecting the lower volumes saved at higher costs. Copyright © 2007 John Wiley & Sons, Ltd.

A$ = Australian dollar. 1 A$ = 0.81 US$ (2007).
Beneficial effect of hydrophilized porous polymer scaffolds in tissue‐engineered cartilage formation
Authors: Ju Young Min , Park Kwideok , Son Jun Sik , Kim Jae‐Jin , Rhie Jong‐Won , Han Dong Keun
Published: October 2007

Three dimensional (3D) porous poly(L‐lactic acid) (PLLA) scaffolds were fabricated using a modified gas foaming method whose effervescent porogens were a mixture of sodium bicarbonate and citric acid. To improve chondrocyte adhesion, the scaffolds were then hydrophilized through oxygen plasma treatment and in situ graft polymerization of acrylic acid (AA). When the physical properties of AA‐grafted scaffolds were examined, the porosity and pore size were 87 ∼ 93% and 100 ∼ 300 μm, respectively. The pore sizes were highly dependent on the varying ratios (w/w) between porogen and polymer solution. Influenced by their pore sizes, the compressive moduli of scaffolds significantly decreased with increasing pore size. The altered surface characteristics were clearly reflected in the reduced water contact angles that meant a significant hydrophilization with the modified polymer surface. Electron spectroscopy for chemical analysis (ESCA) and time‐of‐flight secondary ion mass spectrometer (ToF‐SIMS) also confirmed the altered surface chemistry. When chondrocytes were seeded onto the AA‐grafted PLLA scaffolds, cell adhesion and proliferation were substantially improved as compared to the unmodified scaffolds. The benefit of the modified scaffolds was clear in the gene expressions of collagen type II that was significantly upregulated after 4‐week culture. Safranin‐O staining also identified greater glycosaminoglycan (GAG) deposition in the modified scaffold. The AA‐grafted porous polymer scaffolds were effective for cell adhesion and differentiation, making them a suitable platform for tissue‐engineered cartilage. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008