bluuebunny/crossref_metadata_2025 huggingface dataset:
Diorganotin Salicylaldoximate Clusters: Their Fascinating Chemistry and Structures
Authors: Gielen Marcel , Biesemans Monique , Willem Rudolph , Tiekink Edward R. T.
Published: January 2004

A large variety of small oxotin clusters, characterised as stable crystalline products or solution transients, has been obtained by the reaction of various diorganotin oxides and salicylaldoxime. The structures were investigated by high resolution multinuclear NMR methods and X‐ray crystallography. The predominant trinuclear clusters contain one seven‐ and two five‐coordinate tin atoms and undergo a series of reversible substitution reactions, including those leading to clusters of differing nuclearity, in solution at room temperature. Such a variety of structures is rather unusual in organotin chemistry. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Kinetics and Mechanism of Axial Ligand Substitution of Alkyl Cobaloximes by Substituted Pyridines in Different Solvents
Authors: Alzoubi Basam M. , Hamza Mohamed S. A. , Felluga Alessandro , Randaccio Lucio , Tauzher Giovanni , van Eldik Rudi
Published: January 2004

Ligand‐substitution reactions of trans‐RCo(Hdmg)2S (where R = PhCH2 or CF3CH2, Hdmg = dimethylglyoximate, and S = H2O or MeOH) were studied for the nucleophiles 4‐aminopyridine (4‐NH2Py), pyridine (Py) and 4‐cyanopyridine (4‐CNPy). From the pressure and temperature dependence of the substitution of methanol by 4‐NH2Py, Py, and 4‐CNPy, the activation parameters ΔH≠, ΔS≠, and ΔV≠ were estimated for the cases where R = PhCH2 and CF3CH2. The activation parameters for the substitution of H2O by Py and 4‐CNPy in the case where R = CF3CH2 were also found. The kinetic data and activation parameters show that the dissociative character of the reaction decreases on changing the R group from PhCH2 to CF3CH2 and the solvent from MeOH to H2O. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Cover Picture: Kinetics and Mechanism of Axial Ligand Substitution of Alkyl Cobaloximes by Substituted Pyridines in Different Solvents (Eur. J. Inorg. Chem. 3/2004)
Authors: Alzoubi Basam M. , Hamza Mohamed S. A. , Felluga Alessandro , Randaccio Lucio , Tauzher Giovanni , van Eldik Rudi
Published: January 2004

The cover picture shows the dissociative character of the displacement of a coordinated solvent molecule trans to the alkyl group in cobalt(III) complexes. Details are discussed in the article by R. van Eldik et al. on p. 653 ff. The work has benefited greatly from an international collaboration.
Electrochemistry of DNA at Single‐Wall Carbon Nanotubes
Authors: Wang Jianxiu , Li Meixian , Shi Zujin , Li Nanqiang , Gu Zhennan
Published: January 2004

Single‐wall carbon nanotubes (SWNTs) can be used as an electrochemical probe to study the electrochemical oxidation of DNA, two voltammetric oxidation peaks corresponding to electrochemical oxidation of guanine and adenine residues in DNA could be observed, demonstrating a new potential application of SWNTs in DNA analysis. Compared to other types of electrode materials, the electrochemical response of natural DNA was greatly enhanced at the SWNT‐modified electrode. This method can be used to investigate the interaction of SWNTs with DNA.
Nanotube Membrane Based Biosensors
Authors: Kohli Punit , Wirtz Marc , Martin Charles R.
Published: January 2004

We review highly sensitive detection based on electrochemical methods. These methods are based on monodisperse gold and alumina nanotubule membranes with inside diameter approaching molecular dimensions. The analyte species can be detected by measuring a change in trans‐membrane current when the analyte is added to the nanotubule‐based cell. The second method entails the use of a concentration change based on the nanotubule membrane. Biomemtic ion‐gated channels micropore and nanotubule membrane sensors are also reviewed. These synthetic ion channels can be switched from an “off” state to an “on” state in response to an external chemical stimulus. Using these methods, we have achieved detection limits as low as 10 pM. Potential applications for these biosensors are in fields such as bioanalytical, biomedical, pharmaceutical and drug discovery.
The Electrochemical Behavior of Hemoglobin on SWNTs/DDAB Film Modified Glassy Carbon Electrode
Authors: Yang Peilin , Zhao Qiang , Gu Zhennan , Zhuang Qiankun
Published: January 2004

The SWNTs/DDAB film modified glassy carbon electrode was successfully prepared to study the electrochemical behavior of hemoglobin (Hb). A better electrochemical response was observed than that on the DDAB or SWNTs film modified electrode. Cyclic voltammetry of Hb showed two pairs of well‐defined and nearly reversible peaks. The electrochemical reaction of hemoglobin on the SWNTs/DDAB film modified electrode was controlled by absorption. Using the SWNTs/DDAB film modified electrode, the interaction between hemoglobin and tar was studied.
Constant‐Distance Mode Scanning Electrochemical Microscopy. Part II: High‐Resolution SECM Imaging Employing Pt Nanoelectrodes as Miniaturized Scanning Probes
Authors: Ballesteros Katemann Bernardo , Schulte Albert , Schuhmann Wolfgang
Published: January 2004

The potential of needle‐type Pt disk nanoelectrodes as extremely miniaturized scanning probes for high resolution scanning electrochemical microscopy (SECM) was investigated. The accuracy of a piezoelectric shear‐force based distance control allowed a precise positioning of the Pt nanoelectrodes in close proximity to the surface of interest not only in tip approach experiments but also throughout scanning and SECM imaging. As proof of the advanced quality of SECM imaging, high‐resolution current and topography images of a three‐dimensional LIGA microstructure will be presented both simultaneously acquired by operating Pt nanoelectrodes in the constant‐distance mode of SECM.
A Novel Amperometric O2 Gas Sensor Based on Supported Room‐Temperature Ionic Liquid Porous Polyethylene Membrane‐Coated Electrodes
Authors: Wang Rong , Okajima Takeyoshi , Kitamura Fusao , Ohsaka Takeo
Published: January 2004

A novel solid‐state amperometric O2 gas sensor based on the supported 1‐ethyl‐3‐methylimidazolium tetrafluoroborate (EMIBF4) porous polyethylene membrane‐coated electrodes has been proposed with its characterization. By electrochemical impedance technique, the ionic conductivity of the supported EMIBF4 membrane was estimated to be ca. 0.6 S m−1, indicating that the supported EMIBF4 membrane (the thickness: 50 μm) can be used as a solid state ionic conductor at room temperature. The cyclic voltammograms obtained for the one‐electron redox reaction of O2/O2−.(O2−.: superoxide ion) couple at high scan rates (>100 mV s−1) showed a couple of usual redox peaks, while at low scan rates (<30 mV s−1) S‐shaped steady‐state voltammograms similar to those obtained by rotating disk voltammetry were obtained. These results were explained on the basis of the mass transport of O2 at the supported EMIBF4 membrane‐coated electrode system. The transient and steady‐state reduction currents for the reduction of O2 to O2−.as well as the transient oxidation current for the reoxidation of O2−.to O2, which were obtained by potential‐step chronoamperometry, could be used to measure the change of O2 concentration in O2‐N2 mixed gas stream. The present O2 gas sensor demonstrated a wide detection range, a high sensitivity and an excellent reproducibility.
Attachment of Ferrocene‐Capped Gold Nanoparticle/Streptavidin Conjugates onto Electrode Surfaces Covered with Biotinylated Biomolecules for Enhanced Voltammetric Analysis
Authors: Baca Alfred J. , Zhou Feimeng , Wang Jun , Hu Jingbo , Li Jinhua , Wang Jianxiu , Chikneyan Zarui S.
Published: January 2004

Ferrocene (Fc)‐capped gold nanoparticle/streptavidin conjugates were attached onto electrodes covered with either biotinylated oligodeoxynucleotides (ODNs) duplexes or N‐biotinoyl‐N′‐(6‐maleimidedohexanoyl)hydrazide that had been preadsorbed onto the reduced form of glutathione (GSH) immobilized onto a dithiobissuccinmidyl propionate self‐assembled monolayer (SAM). Effects of the DNA probe and target strand lengths on the voltammetric behavior of the Fc groups residing at the nanoparticle conjugates were studied. The voltammetric behavior was also compared to that arising from the Fc groups present at the end of the ODN duplex in a sandwich complex (Wang et al. Anal. Chem. 2003, 75, 3941). It was found that shorter duplexes would lead to a more reversible voltammetric wave. However, the formation of duplexes with a greater number of base pairs will result in a lower detection level. For the analysis of a biotinylated 30mer target at a mixed SAM of a 30mer probe and hexanethiol, a concentration level as low as 0.25 pM could be detected (which is even lower than our previously reported detection level of 2 pM for an ODN sandwich complex). The detection level for GSH (1 nM) was found to be comparable to those of many other analytical techniques. The capability of our method for trace analysis of biotinylated biomolecules can be attributed to the enhanced voltammetric detection by the large number of Fc moieties present at each conjugate. The method described herein is simple, reproducible, versatile, and selective, and does not require sophisticated analytical instrumentation.
Electrochemical Detection of PCR Amplicons Using Electroconductive Polymer Modified Electrode and Multiple Nanoparticle Labels
Authors: Li Lu‐Lu , Cai Hong , Lee Thomas Ming‐Hung , Barford John , Hsing I‐Ming
Published: January 2004

We report the utilization of an oligonucleotide‐functionalized electroconducting polymer, coupled with a nanoparticle‐based hybridization indicator for a sensitive detection of multi‐labeled PCR amplicons. The electroconducting polymer permits the immobilization of an active probe onto the transducer surface. In this work, 2‐aminobenzoic acid is electropolymerized onto an indium tin oxide electrode. The coated film has carboxyl groups for the immobilization of amino‐terminated probe, mediated by coupling agents of water‐soluble carbodiimide and N‐hydroxysulfosuccinimide. This coupling chemistry has minimal nonspecific adsorption of the gold nanoparticle indicator, leading to a low background signal allowing a more sensitive hybridization detection. Signal transduction of the hybridization event is achieved through a series of steps: i) the binding of the gold nanoparticle label to the hybridized target based on streptavidin‐biotin interaction, ii) the catalytic silver deposition onto the gold label (i.e., the silver enhancement) and iii) potentiometric stripping analysis of the deposited silver. In addition to signal amplification by silver enhancement, multiple‐labeling of the amplicons by the incorporation of biotin‐16‐dUTP is employed to further enhance the signal to background ratio. The sequence‐specific identification of both symmetric and asymmetric PCR amplicons is also demonstrated.
Electrochemistry in the Presence of Mesoporous TiO2 Phytate Nanofilms
Authors: McKenzie Katy J. , Marken Frank , Oyama Munetaka , Gardner Catherine E. , Macpherson Julie V.
Published: January 2004

Thin composite organic – inorganic membranes are formed at electrode surfaces via a layer‐by‐layer deposition process employing TiO2 nanoparticles and phytic acid as molecular binder. The mesoporous membranes form uniformly across platinum and glass surfaces and are shown via conducting atomic force microscopy (C‐AFM) to behave in dry state as electrically insulating films. Voltammetry at platinum electrodes of 1.5 mm, 100 μm, and 10 μm diameter is used to survey the effect of the composite membrane on electrochemical processes. The electrode diameter as well as concentration and nature of electrolyte have a considerable effect on the electrode process. For the one electron reduction of Ru(NH3)$\rm{ {_{6}^{3+}}}$ in aqueous media adsorption effects, mobility effects, and accumulation or ‘memory’ effects are observed. Similarly, protons or cationic molecules such as dopamine can be accumulated and ‘stored’ in the membrane and then transferred to a clean electrolyte for analysis.
Amplified Electrical Transduction of DNA Hybridization Based on Polymeric Beads Loaded with Multiple Gold Nanoparticle Tags
Authors: Kawde Abdel‐Nasser , Wang Joseph
Published: January 2004

A new strategy for amplifying particle‐based electrical DNA detection based on oligonucleotides functionalized with polymeric beads carrying numerous gold nanoparticle tags is described. The gold‐tagged beads were prepared by binding biotinylated metal nanoparticles to streptavidin‐coated polystyrene spheres. Such use of carrier‐sphere amplification platforms is combined with catalytic enlargement of the multiple gold tags and an ultrasensitive electrochemical stripping detection of the dissolved gold tags. The gold‐nanoparticle loaded beads and the resulting DNA‐linked assembly were characterized by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Factors affecting the performance have been optimized. Such amplified electrical transduction allows detection of DNA targets down to the 300amol level, and offers great promise for ultrasensitive detection of other biorecogntion events.
Sensing with Nafion Coated Carbon Nanotube Field‐Effect Transistors
Authors: Star Alexander , Han Tzong‐Ru , Joshi Vikram , Stetter Joseph R.
Published: January 2004

Sequential CVD and CMOS processes were used to make a FET that has single walled carbon nanotubes to serve as the conducting source to drain channel. This structure can be decorated to provide gas and liquid responses and herein is evaluated as a humdity sensor. The Na+, K+, and Ca2+ ion‐exchanged Nafion polymer acts as the chemically sensitive layer in this electrochemical sensor. The effect of gate voltage on the charge‐sensitive NT structure was found to be RH dependent over the range of 12–93% RH with msec response time.
Nanoengineered Encapsulation of Mediator Microcrystals and Their Use as a Non‐metallic Label System for the Silver Enhancement Technique
Authors: Cheung Mak Wing , Li Yongjun , Keung Lau Wan , Trau Dieter
Published: January 2004

We report on the nanoengineered encapsulation and functionalization of mediator microcrystals and their use as a non‐metallic bioassay label system for the silver enhancement technology. Mediator microcrystals were encapsulated and functionalized by using a Layer‐by‐Layer (LbL) based approach. This is a generic way to transform most low‐soluble mediators (e.g., ferroceneacetic acid) into a label for electrochemical bioassays. Instead of using conventional gold particles, encapsulated mediator microcrystals are used as the primary label for the silver enhancement technique. After the biorecognition reaction the unbound labels were separated and a silver(I) ion solution was added. The mediator reduces silver ions into metallic silver and the mediator microcrystal was transformed into a silver particle. Consecutively a reducing agent was added leading to a further silver growth, representing the silver enhancement step. A large amount of silver was developed from the mediator, resulting in signal amplification. The amount of developed silver was studied in a bioassay and was found proportional to the analyte concentration.
Electroanalytical and Bioelectroanalytical Systems Based on Metal and Semiconductor Nanoparticles
Authors: Katz Eugenii , Willner Itamar , Wang Joseph
Published: January 2004

Metal, semiconductor and magnetic particles act as functional units for electroanalytical applications. Metal nanoparticles provide three important functions for electroanalysis. These include the roughening of the conductive sensing interface, the catalytic properties of the nanoparticles permiting their enlargement with metals and the amplified electrochemical detection of the metal deposits and the conductivity properties of nanoparticles at nanoscale dimensions that allow the electrical contact of redox‐centers in proteins with electrode surfaces. Also, metal and semiconductor nanoparticles provide versatile labels for amplified electroanalysis. Dissolution of the nanoparticle labels and the electrochemical collection of the dissolved ions on the electrode followed by the stripping‐off of the deposited metals represents a general electroanalytical procedure. These unique functions of nanoparticles were employed for developing electrochemical gas sensors, electrochemical sensors based on molecular‐ or polymer‐functionalized nanoparticle sensing interfaces, and for the construction of different biosensors including enzyme‐based electrodes, immunosensors and DNA sensors. Semiconductor nanoparticles enable the photoelectrochemical detection of analytes. Several studies have revealed the photocurrent generation by enzyme‐mediated processes and as a result of DNA hybridization. Magnetic particles act as functional components for the separation of biorecognition complexes and for the amplified electrochemical sensing of DNA or antigen/antibody complexes. Also, electrocatalytic and bioelectrocatalytic processes at electrode surfaces are switched by means of functionalized magnetic particles and in the presence of an external magnet.
Disposable Carbon Nanotube Modified Screen‐Printed Biosensor for Amperometric Detection of Organophosphorus Pesticides and Nerve Agents
Authors: Lin Yuehe , Lu Fang , Wang Joseph
Published: January 2004

A disposable carbon nanotube‐based biosensor was successfully developed and applied to the detection of organophosphorus (OP) pesticides and nerve agents. The biosensors using acetycholinesterase (AChE)/choline oxidase (CHO) enzymes provided a high sensitivity, large linear range, and low detection limits for the analysis of OP compounds. Such characteristics may be attributed to the catalytic activity of carbon nanotube to promote the redox reaction of hydrogen peroxide produced during AChE/CHO enzymatic reactions with their substrate, as well as the large surface area of carbon nanotube materials.
Analysis of RING finger genes required for embryogenesis in C. elegans
Authors: Moore Rhonda , Boyd Lynn
Published: January 2004

The RING finger motif exists in E3 ligases of the ubiquitination pathway. These ubiquitin ligases bind to target proteins, leading to their modification by covalent addition of ubiquitin peptides. Current databases contain hundreds of proteins with RING finger motifs. This study investigates the role of RING finger genes in embryogenesis of the nematode, Caenorhabditis elegans. We expand the previous list of RING finger‐containing genes and show that there are 103 RING finger‐containing genes in the C. elegans genome. DNA microarrays of these 103 genes were probed with various RNA samples to identify 16 RING finger genes whose expression is enriched in the germline. RNA interference (RNAi) analysis was then used to determine the developmental role of these genes. One RING finger gene, C32D5.10, showed a dramatic larval arrest upon RNAi. Three RING finger genes exhibited embryonic lethality after RNAi. These three genes include par‐2, and two small RING finger proteins: F35G12.9 (an ortholog of APC11) and ZK287.5 (an ortholog of rbx1). Embryos from RNAi of the APC11 and rbx1 orthologs were arrested in the cell cycle, confirming the role of these particular RING finger proteins in regulation of the cell cycle. genesis 38:1–12, 2004. © 2003 Wiley‐Liss, Inc.
Zebrafish intestinal fatty acid binding protein (I‐FABP) gene promoter drives gut‐specific expression in stable transgenic fish
Authors: Her Guor Mour , Chiang Chia‐Chang , Wu Jen‐Leih
Published: January 2004

Mammalian intestinal fatty acid‐binding protein (I‐FABP) is a small cytosolic protein and is thought to play a crucial role of intracellular fatty acid trafficking and metabolism in gut. To establish an in vivo system for investigating its tissue‐specific regulation during zebrafish intestinal development, we isolated 5′‐flanking sequences of the zebrafish L‐FABP gene and used a transgenic strategy to generate gut‐specific transgenic zebrafish with green/red fluorescent intestine. The 4.5‐kb 5′‐flanking sequence of zebrafish I‐FABP gene was sufficient to direct fluorescent expression in intestinal tube, first observed in 3 dpf embryos and then continuously to the adult stage. This pattern of transgenic expression is consistent with the expression pattern of the endogenous gene. In all five transgenic lines 45–52% of the F2 inheritance rates were consistent with the ratio of Mendelian segregation. These fish can also provide a valuable resource of labeled adult intestinal cells for in vivo or in vitro studies. Finally, it is possible to establish an in vivo system using these fish for screening genes required for gut development. genesis 38:26–31, 2004. © 2003 Wiley‐Liss, Inc.
General method for the modification of different BAC types and the rapid generation of BAC transgenic mice
Authors: Sparwasser Tim , Gong Shiaoching , Li James Y.H. , Eberl Gerard
Published: January 2004

Most genome projects have relied on the sequencing of bacterial artificial chromosomes (BACs), which encompass 100–300 kb of genomic DNA. As a consequence, several thousand BAC clones are now mapped to the human and mouse genome. It is therefore possible to identify in silico a BAC clone that carries a particular gene and obtain it commercially. Given the large size of BACs, most if not all regulatory sequences of a gene are present and can be used to direct faithful and tissue‐specific expression of heterologous genes in vitro in cell cultures and in vivo in BAC‐transgenic mice. We describe here an optimized and comprehensive protocol to select, modify, and purify BACs in order to generate BAC‐transgenic mice. Importantly, this protocol includes a method to generate, within 2 days, complex plasmid cassettes required to modify BACs, and to efficiently modify different types of BACs selected from the two major BAC libraries available. Altogether, using a combination of genomic database analysis, overlap PCR cloning, and BAC recombination in bacteria, our approach allows for the rapid and reliable generation of “pseudo knockin” mice. genesis 38:39–50, 2004. © 2003 Wiley‐Liss, Inc.
Histone deacetylase activity is required for embryonic stem cell differentiation
Authors: Lee Jeong‐Heon , Hart Suzanne R.L. , Skalnik David G.
Published: January 2004

Mammalian development requires commitment of cells to restricted lineages, which requires epigenetic regulation of chromatin structure. Epigenetic modifications were examined during in vitro differentiation of murine embryonic stem (ES) cells. Global histone acetylation, a euchromatin marker, declines dramatically within 1 day of differentiation induction and partially rebounds by day 2. Histone H3‐Lys9 methylation, a heterochromatin marker, increases during in vitro differentiation. Conversely, the euchromatin marker H3‐Lys4 methylation transiently decreases, then increases to undifferentiated levels by day 4, and decreases by day 6. Global cytosine methylation, another heterochromatin marker, increases slightly during ES cell differentiation. Chromatin structure of the Oct4 and Brachyury gene promoters is modulated in concert with their pattern of expression during ES cell differentiation. Importantly, prevention of global histone deacetylation by treatment with trichostatin A prevents ES cell differentiation. Hence, ES cells undergo functionally important global and gene‐specific remodeling of chromatin structure during in vitro differentiation. genesis 38:32–38, 2004. © 2003 Wiley‐Liss, Inc.
When Gods Become Visible
Authors: Demmer Ulrich , Heidemann Frank
Published: January 2004

The Jenu Kurumba are hunters and gatherers. Their tribal rituals reveal surprising aspects of the social system of this Indian community
Momentum for Research in Europe
Authors: Winnacker Ernst‐Ludwig
Published: January 2004

On the road to becoming the most dynamic knowledge‐based economy in the world — Increasing competition for the best minds
Of Aphids and Ants
Authors: Hoffmann Klaus , Fischer Melanie , Völkl Wolfgang , Lorenz Matthias W.
Published: January 2004

Aphids produce honeydew from the liquids of their host plant. Ants love this sugary substance
The Capercaillie and the Question of Survival
Authors: Storch Ilse
Published: January 2004

Where once continuous woodlands existed, only islands now remain in a sea of open countryside. What impact does this have on species such as the capercaillie?
The Whole Extent of the Antarctic
Authors: Borch René , Mayer Michael , Lindner Klaus , Depenthal Claudia , Heck Bernhard
Published: January 2004

A satellite navigation system is giving geoscientists precise information about the uplift and subsidence movements of the Antarctic continent
Caesar's Waterworks
Authors: Fahlbusch Henning , Manderscheid Hubertus , Ohlig Christoph
Published: January 2004

Emperor Hadrian's spacious residence still makes an impression today. How the complex got its water supply is of interest to more than just archaeologists
Androgen receptor: A key molecule in the progression of prostate cancer to hormone independence
Authors: Taplin Mary‐Ellen , Balk Steven P.
Published: January 2004

Despite earlier detection and recent advances in surgery and radiation, prostate cancer is second only to lung cancer in male cancer deaths in the United States. Hormone therapy in the form of medical or surgical castration remains the mainstay of systemic treatment in prostate cancer. Over the last 15 years with the clinical use of prostate specific antigen (PSA), there has been a shift to using hormone therapy earlier in the disease course and for longer duration. Despite initial favorable response to hormone therapy, over a period of time these tumors will develop androgen‐independence that results in death. The androgen receptor (AR) is central to the initiation and growth of prostate cancer and to its response to hormone therapy. Analyses have shown that AR continues to be expressed in androgen‐independent tumors and AR signaling remains intact as demonstrated by the expression of the AR regulated gene, PSA. Androgen‐independent prostate cancers have demonstrated a variety of AR alterations that are either not found in hormone naïve tumors or found at lower frequency. These changes include AR amplification, AR point mutation, and changes in expression of AR co‐regulatory proteins. These AR changes result in a “super AR” that can respond to lower concentrations of androgens or to a wider variety of agonistic ligands. There is also mounting evidence that AR can be activated in a ligand independent fashion by compounds such as growth factors or cytokines working independently or in combination. These growth factors working through receptor tyrosine kinase pathways may promote AR activation and growth in low androgen environments. The clinical significance of these AR alterations in the development and progression of androgen‐independent prostate cancer remains to be determined. Understanding the changes in AR signaling in the evolution of androgen‐independent prostate cancer will be key to the development of more effective hormone therapy. © 2003 Wiley‐Liss, Inc.
Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer
Authors: Ghosh Arundhati , Heston Warren D.W.
Published: January 2004

Prostate specific membrane antigen (PSMA), is a unique membrane bound glycoprotein, which is overexpressed manifold on prostate cancer as well as neovasculature of most of the solid tumors, but not in the vasculature of the normal tissues. This unique expression of PSMA makes it an important marker as well as a large extracellular target of imaging agents. PSMA can serve as target for delivery of therapeutic agents such as cytotoxins or radionuclides. PSMA has two unique enzymatic functions, folate hydrolase and NAALADase and found to be recycled like other membrane bound receptors through clathrin coated pits. The internalization property of PSMA leads one to consider the potential existence of a natural ligand for PSMA. In this review we have discussed the regulation of PSMA expression within the cells, and significance of its expression in prostate cancer and metastasis. © 2003 Wiley‐Liss, Inc.
Prostate carcinoma: Opportunities for translational research
Authors: FitzGerald T.J. , Simon Edmund , Meyer Joshua
Published: January 2004

Adenocarcinoma of the prostate continues to be a major health concern. Although modern screening techniques have increased the number of men presenting with early stage disease, a significant population of men will present with intermediate or advanced pathological risk factors for recurrence. There are defined limitations in outcome with traditional therapies including surgery, radiation therapy, and hormone manipulation. Patients with intermediate and high‐risk factors for treatment failure are candidates for protocols using translational research strategies incorporated into studies currently in development. These strategies may be able to selectively treat expression products of tumor and thus be more selective in the target for treatment. Carefully designed studies using these translational strategies have great potential in improving clinical outcome, tumor kill, and normal tissue tolerance in the care of these patients. © 2003 Wiley‐Liss, Inc.
Prostate cancer association studies: Pitfalls and solutions to cancer misclassification in the PSA era
Authors: Platz Elizabeth A. , De Marzo Angelo M. , Giovannucci Edward
Published: January 2004

Widespread screening of American men for elevated PSA has changed the characteristics of prostate cancer cases in the U.S. The influence of the changed nature of prostate cancer cases in the PSA era and the need for careful consideration of who is a “case” and who is a “control” on the ability to detect associations of risk factors with prostate cancer in etiologic epidemiologic studies merits discussion. Issue 1: prostate cancer cases diagnosed in the PSA era are enriched with a pool of early lesions, which may differ in etiology, and are deficient in advanced lesions, which are the most likely to be the product of promotion and progression events. By admixing the two types of cases (i.e., imperfect specificity), the associations previously detected using epidemiologic designs when the majority of cases were clinically detected may no longer be apparent in the PSA era when the majority of cases are now detected in the pre‐clinical phase. Researchers must now tailor hypotheses such that they are testable using early stage cases or specifically augment the number of advanced cases when testing hypotheses related to extraprostatic growth and progression. Issue 2: even when controls are screened for elevated PSA to rule out the presence of prostate cancer, some proportion of those controls currently will have one or more foci of prostate cancer. The imperfect sensitivity of the PSA test coupled with diagnostic work‐up may in part result from (a) lack of PSA elevation in some men with prostate cancer or (b) failure of biopsy to sample the tumor focus in men with elevated PSA. Misclassification of men with undetected prostate cancer as controls usually produces a bias that tends to deflate associations. Given this type of disease misclassification, whether an association still can be statistically detected depends on the extent of misclassification, the magnitude of the true association, the prevalence of the exposure in the true controls, and the sample size, although in general moderate nondifferential misclassification does not lead to profound attenuation. However, under the same scenario attenuation does not occur in cohort or case‐cohort studies in which the rate or risk ratio (RR) is calculated. That prostate cancer cases diagnosed in the PSA era are enriched with early stage, minimally invasive disease in our opinion is likely to pose a far more serious obstacle to epidemiologic research on the etiology of clinically important prostate cancer than the issue of inclusion as controls some men who have undiagnosed prostate cancer because of imperfect sensitivity of PSA screening and biopsy sampling error. © 2003 Wiley‐Liss, Inc.
Angiopoietin 1, PDGF‐B, and TGF‐β gene regulation in endothelial cell and smooth muscle cell interaction
Authors: Nishishita Toshishita , Lin Pengnian Charles
Published: January 2004

The vascular wall is mainly composed of endothelial cells (ECs) and smooth muscle cells (SMCs). The crosstalking between these two cell types is critical in the vascular maturation process. Genetic studies suggest that the Tie2/angiopoietin 1 (Ang1) pathway regulates vascular remodeling. However, the molecular mechanism is unclear. PDGF is a potent chemoattractant for SMCs, and TGF‐β regulates SMC differentiation. Here, we examined gene regulation. PDGF‐B stimulation upregulated Ang1 expression in SMCs through the PI3K and PKC pathways. PDGF‐B stimulation also produced an acute induction of TGF‐β expression in SMCs through the MAPK/ERK pathway. Interestingly, TGF‐β negatively regulated Ang1 expression induced by the PDGF‐B stimulation in SMCs. Reciprocally, we observed that stimulation of ECs with either Ang1 or TGF‐β slightly downregulated PDGF expression. A combination of both TGF‐β with Ang1 produced much stronger downregulation of PDGF. Our data showed complex gene regulations that include both positive and negative regulations between ECs and SMCs to maintain vascular homeostasis. © 2003 Wiley‐Liss, Inc.
Chemoprevention of prostate cancer with selenium: An update on current clinical trials and preclinical findings
Authors: Meuillet Emmanuelle , Stratton Suzanne , Prasad Cherukuri Durga , Goulet Anne‐Christine , Kagey Jacob , Porterfield Bruce , Nelson Mark A.
Published: January 2004

Prostate cancer is the most common cancer diagnosed and the second leading cause of cancer‐related deaths in men in the United States. The etiological factors that give rise to prostate cancer are not known. Therefore, it is not possible to develop primary intervention strategies to remove the causative agents from the environment. However, secondary intervention strategies with selenium (Se) compounds and other agents represent a viable option to reduce the morbidity and mortality of prostate cancer. In this review, we discuss ongoing clinical trials. In addition, we discuss preclinical mechanistic studies that provide insights into the biochemical and molecular basis for the anti‐carcinogenic activity of both inorganic and organic forms of Se. © 2003 Wiley‐Liss, Inc.
GSTP1 CpG island hypermethylation as a molecular biomarker for prostate cancer
Authors: Nakayama Masashi , Gonzalgo Mark L. , Yegnasubramanian Srinivasan , Lin Xiaohui , De Marzo Angelo M. , Nelson William G.
Published: January 2004

Somatic hypermethylation of CpG island sequences at GSTP1, the gene encoding the π‐class glutathione S‐transferase, appears to be characteristic of human prostatic carcinogenesis. To consider the potential utility of this epigenetic alteration as a biomarker for prostate cancer, we present here a comprehensive review of the literature describing somatic GSTP1 changes in DNA from prostate cells and tissues. GSTP1 CpG island hypermethylation has been detected in prostate cancer DNA using a variety of assay techniques, including (i) Southern blot analysis (SB), after treatment with 5‐mC‐sensitive restriction endonucleases, (ii) the polymerase chain reaction, following treatment with 5‐mC‐sensitive restriction endonucleases (RE‐PCR), (iii) bisulfite genomic sequencing (BGS), and (iv) bisulfite modification followed by the polymerase chain reaction, using primers selective for target sequences containing 5‐mC (MSP). In the majority of the case series so far reported, GSTP1 CpG island hypermethylation was present in DNA from at least 90% of prostate cancer cases. When analyses have been carefully conducted, GSTP1 CpG island hypermethylation has not been found in DNA from normal prostate tissues, or from benign prostatic hyperplasia (BPH) tissues, though GSTP1 CpG island hypermethylation changes have been detected in DNA from candidate prostate cancer precursor lesions proliferative inflammatory atrophy (PIA) and prostatic intraepithelial neoplasia (PIN). Using PCR methods, GSTP1 CpG island hypermethylation has also been detected in urine, ejaculate, and plasma from men with prostate cancer. GSTP1 CpG island hypermethylation, a somatic epigenetic alteration, appears poised to serve as a molecular biomarker useful for prostate cancer screening, detection, and diagnosis. © 2003 Wiley‐Liss, Inc.
Pathological and molecular mechanisms of prostate carcinogenesis: Implications for diagnosis, detection, prevention, and treatment
Authors: De Marzo Angelo M. , DeWeese Theodore L. , Platz Elizabeth A. , Meeker Alan K. , Nakayama Masashi , Epstein Jonathan I. , Isaacs William B. , Nelson William G.
Published: January 2004

Prostate cancer is an increasing threat throughout the world. As a result of a demographic shift in population, the number of men at risk for developing prostate cancer is growing rapidly. For 2002, an estimated 189,000 prostate cancer cases were diagnosed in the U.S., accompanied by an estimated 30,200 prostate cancer deaths [Jemal et al., 2002]. Most prostate cancer is now diagnosed in men who were biopsied as a result of an elevated serum PSA (>4 ng/ml) level detected following routine screening. Autopsy studies [Breslow et al., 1977; Yatani et al., 1982; Sakr et al., 1993], and the recent results of the Prostate Cancer Prevention Trial (PCPT) [Thompson et al., 2003], a large scale clinical trial where all men entered the trial without an elevated PSA (<3 ng/ml) were subsequently biopsied, indicate the prevalence of histologic prostate cancer is much higher than anticipated by PSA screening. Environmental factors, such as diet and lifestyle, have long been recognized contributors to the development of prostate cancer. Recent studies of the molecular alterations in prostate cancer cells have begun to provide clues as to how prostate cancer may arise and progress. For example, while inflammation in the prostate has been suggested previously as a contributor to prostate cancer development [Gardner and Bennett, 1992; Platz, 1998; De Marzo et al., 1999; Nelson et al., 2003], research regarding the genetic and pathological aspects of prostate inflammation has only recently begun to receive attention. Here, we review the subject of inflammation and prostate cancer as part of a “chronic epithelial injury” hypothesis of prostate carcinogenesis, and the somatic genome and phenotypic changes characteristic of prostate cancer cells. We also present the implications of these changes for prostate cancer diagnosis, detection, prevention, and treatment. © 2003 Wiley‐Liss, Inc.
Distinctive regulation and function of PI 3K/Akt and MAPKs in doxorubicin‐induced apoptosis of human lung adenocarcinoma cells
Authors: Zhao Yanqiu , You Han , Yang Yu , Wei Lin , Zhang Xin , Yao Libo , Fan Daiming , Yu Qiang
Published: January 2004

Regulation and function of PI 3K/Akt and mitogen‐activated protein kinases (MAPKs) in doxorubicin‐induced cell death were investigated in human lung adenocarcinoma cells. Doxorubicin induced dose‐dependent apoptosis of human lung adenocarcinoma NCI‐H522 cells. Prior to cell death, both Akt and the MAPK family members (MAPKs: ERK1/2, JNK, and p38) were activated in response to the drug treatment. The kinetics of the inductions for Akt and MAPKs are, however, distinct. The activation of Akt was rapid and transient, activated within 30 min of drug addition, then declined after 3 h, whereas the activations of three MAPKs occurred later, 4 h after addition of the drug and sustained until cell death occurred. Inhibition of PI 3K/Akt activation had no effect on MAPKs' activation, suggesting that the two pathways are independently activated in response to the drug treatment. Inhibition of PI 3K/Akt and p38 accelerated and enhanced doxorubicin‐induced cell death. On the contrary, inhibition of ERK1/2 or JNK had no apparent effect on the cell death. Taken together, these results suggest that PI 3K/Akt and MAPKs signaling pathways are all activated, but with distinct mechanisms, in response to doxorubicin treatment. Activation of PI 3K/Akt and p38 modulates apoptotic signal pathways and inhibits doxorubicin‐induced cell death. These responses of tumor cells to cancer drug treatment may contribute to their drug resistance. Understanding of the mechanism and function of the responses will be beneficial for the development of novel therapeutic approaches for improvement of drug efficacy and circumvention of drug resistance. © 2003 Wiley‐Liss, Inc.
A LIM protein, Hic‐5, functions as a potential coactivator for Sp1
Authors: Shibanuma Motoko , Kim‐Kaneyama Joo‐ri , Sato Shotaro , Nose Kiyoshi
Published: January 2004

Hic‐5 is a LIM protein with striking similarity to paxillin, and shuttles between focal adhesions and the nucleus. Our previous study suggested that Hic‐5 participates in the transcriptional control of several genes such as the c‐fos and p21 genes. In the present study, we examined the function of Hic‐5 in the nucleus using the transcriptional promoter region of the p21 gene. When localized to the nucleus, Hic‐5 was found to transactivate the p21 promoter through two of five Sp1 sites in the region proximal to the TATA box. The Hic‐5 effect was mediated by a transactivation domain of Sp1 and functional interaction with p300 through the LIM4 domain. Hic‐5 was also shown to interact functionally and physically with Smad3 through the LIM domains and to potentiate p21 promoter activity together with Smad3 and Sp1. These properties were confirmed in an artificial system using GAL4‐fusion protein. Thus, Hic‐5 was suggested to have a potential function as a cofactor in the transcriptional complex that contains Sp1, playing a role in gene transcription in the nucleus as well as in integrin signaling at focal adhesion sites. © 2004 Wiley‐Liss, Inc.
Hydrocortisone increases the rate of differentiation of cultured human osteoblasts
Authors: Ireland Deborah C. , Bord Sharyn , Beavan Siân R. , Compston Juliet E.
Published: January 2004

Reduced bone formation is the main finding in glucocorticoid‐induced osteoporosis. The aim of this study was to determine whether differentiation of cultured human osteoblasts is inhibited by high concentrations of hydrocortisone. We measured the levels of mRNAs for three markers of cellular differentiation, type 1 collagen (COL1), alkaline phosphatase (ALP), and osteocalcin (OC), in four lines of human osteoblasts from female donors cultured with doses of hydrocortisone from 0 μM to 4 μM. The change in ALP/COL1 mRNA ratio over a given time was used to determine the average rate of differentiation of the cells in a culture. Although basal expression profiles and their changes with time were different for the different cell lines, all cell lines showed a dose‐dependent rise in the rate of increase of ALP mRNA relative to COL1 mRNA. However, increase in OC mRNA with time, seen here only in young donor hOBs, was significantly inhibited by 4 μM hydrocortisone, indicating that hydrocortisone can inhibit OC expression while promoting cellular differentiation. The data suggest that increasing concentrations of glucocorticoid, including concentrations similar to plasma levels in patients receiving oral glucocorticoid therapy, increase the rate of cellular differentiation. © 2003 Wiley‐Liss, Inc.
Estrogens and anti‐estrogens: Key mediators of prostate carcinogenesis and new therapeutic candidates
Authors: Ho Shuk‐Mei
Published: January 2004

Despite the historical use of estrogens in the treatment of prostate cancer (PCa) little is known about their direct biological effects on the prostate, their role in carcinogenesis, and what mechanisms mediate their therapeutic effects on PCa. It is now known that estrogens alone, or in synergism with an androgen, are potent inducers of aberrant growth and neoplastic transformation in the prostate. The mechanisms of estrogen carcinogenicity could be mediated via induction of unscheduled cell proliferation or through metabolic activation of estrogens to genotoxic metabolites. Age‐related changes and race‐/ethnic‐based differences in circulating or locally formed estrogens may explain differential PCa risk among different populations. Loss of expression of estrogen receptor (ER)‐β expression during prostate carcinogenesis and prevention of estrogen‐mediated oxidative damage could be exploited in future PCa prevention strategies. Re‐expression of ER‐β in metastatic PCa cells raises the possibility of using ER‐β‐specific ligands in triggering cell death in these malignant cells. A variety of new estrogenic/anti‐estrogenic/selective estrogen receptor modulator (SERM)‐like compounds, including 2‐methoxyestradiol, genistein, resveratrol, licochalcone, Raloxifene, ICI 182,780, and estramustine are being evaluated for their potential in the next generation of PCa therapies. Increasing numbers of patients self‐medicate with herbal formulations such as PC‐SPES. Some of these compounds are selective ER‐β ligands, while most of them have minimal interaction with ER‐α. Although many may inhibit testosterone production by blockade of the hypothalamal–pituitary–testis axis, the most effective agents also exhibit direct cytostatic, cytotoxic, or apoptotic action on PCa cells. Some of them are potent in interfering with tubulin polymerization, blocking angiogenesis and cell motility, suppressing DNA synthesis, and inhibiting specific kinase activities. Further discovery of other compounds with potent apoptotic activities but minimal estrogen action should promote development of a new generation of effective PCa preventive or treatment regimens with few or no side‐effects due to estrogenicity. Further advancement of our knowledge of the role of estrogens in prostate carcinogenesis through metabolic activation of estrogens and/or ER‐mediated pathways will certainly result in better preventive or therapeutic modalities for PCa. © 2003 Wiley‐Liss, Inc.
Approaches to understanding the importance and clinical implications of peroxisome proliferator‐activated receptor gamma (PPARγ) signaling in prostate cancer
Authors: Jiang Ming , Shappell Scott B. , Hayward Simon W.
Published: January 2004

The development and maintenance of the prostate are dependent upon a complex series of interactions occurring between the epithelial and stromal tissues (Hayward and Cunha [2000]: Radiol. Clin. N. Am. 38:1–14). During the process of prostatic carcinogenesis, there are progressive changes in the interactions of the nascent tumor with its surrounding stroma and extracellular matrix. These include the development of a reactive stromal phenotype and the possible promotion, by stromal cells, of epithelial proliferation and loss of differentiated function (Hayward et al. [1996]: Ann. N. Y. Acad. Sci. 784:50–62; Grossfeld et al. [1998]: Endocr. Related Cancer 5:253–270; Rowley [1998]: Cancer Metastasis Rev. 17:411–419; Tuxhorn et al. [2002]: Clin. Cancer Res. 8:2912–2923). Many molecules play an as yet poorly defined role in establishing and maintaining a growth quiescent glandular structure in the adult. Peroxisome proliferator‐activated receptor gamma (PPARγ) is a candidate regulator of prostatic epithelial differentiation and may play a role in restricting epithelial proliferation. PPARγ agonists are relatively non‐toxic and have been used with limited success to treat some prostate cancer patients. We would propose that a more complete understanding of PPARγ biology, particularly in the context of appropriate stromal–epithelial and host–tumor interactions would allow for the selection of patients most likely to benefit from this line of therapy. In particular, it seems reasonable to suggest that the patients most likely to benefit may be those with relatively indolent low stage disease for whom this line of therapy could be a useful additive to watchful waiting. © 2003 Wiley‐Liss, Inc.