bluuebunny/crossref_metadata_2025 huggingface dataset:
Edulisones A and B, Two Epimeric Benzo[b]oxepine Derivatives from the Bark of Aglaia edulis
Authors: Kinghorn A. Douglas
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Catalyst‐Controlled Asymmetric Synthesis of Fostriecin (Ia) and 8‐epi‐Fostriecin (Ib).
Authors: Maki Keisuke , Motoki Rie , Fujii Kunihiko , Kanai Motomu , Kobayashi Takayasu , Tamura Shinri , Shibasaki Masakatsu
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Comparing the Information Content of Two Large Olfactory Databases.
Authors: Pintore Marco , Wechman Christophe , Sicard Gilles , Chastrette Maurice , Amaury Nicolas , Chretien Jacques R.
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
A Simple Algorithm for Unique Representation of Chemical Structures—Cyclic/Acyclic Functionalized Achiral Molecules.
Authors: Prabhakar Yenamandra S. , Balasubramanian Krishnan
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Quantitative Structure—Activity Relationship Modeling of Juvenile Hormone Mimetic Compounds for Culex pipiens Larvae, with a Discussion of Descriptor‐Thinning Methods.
Authors: Basak Subhash C. , Natarajan Ramanathan , Mills Denise , Hawkins Douglas M. , Kraker Jessica J.
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
A Physicochemical Model for Analyzing DNA Sequences.
Authors: Dutta Samrat , Singhal Poonam , Agrawal Praveen , Tomer Raju , Kritee Kritee , Khurana Ekta , Jayaram B.
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Proteomics and Bioinformatics Strategies to Design Countermeasures Against Infectious Threat Agents.
Authors: Khan Akbar S. , Mujer Cesar V. , Alefantis Timothy G. , Connolly Joseph P. , Mayr Ulrike Beate , Walcher Petra , Lubitz Werner , DelVecchio Vito G.
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
A Facile Preparation of Nanocrystalline Mo2C from Graphite or Carbon Nanotubes.
Authors: Yang Zeheng , Cai Peijun , Shi Liang , Gu Yunle , Chen Luyang , Qian Yitai
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Ionic Liquids—Media for Unique Phosphorus Chemistry.
Authors: Amigues Eric , Hardacre Christopher , Keane Gillian , Migaud Marie , O'Neill Maeve
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
N‐(4‐{[4‐(1H‐Benzoimidazol‐2‐yl)‐arylamino]‐methyl}‐phenyl)‐benzamide Derivatives as Small Molecule Heparanase Inhibitors.
Authors: Miao Hua‐Quan , et al. et al.
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Novel Histamine H3 Receptor Antagonists Based on the 4‐[(1H‐Imidazol‐4‐yl)methyl]piperidine Scaffold.
Authors: Berlin Michael , et al. et al.
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Processing and Modeling of Novel Nanocrystalline Soft Magnetic Materials
Authors: Suzuki Kiyonori
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Optical and Magnetic Properties of Metal Oxides
Authors: Ishihara Sumio
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Theory of Successive Transitions in Vanadium Spinels and Order of Orbitals and Spins
Authors: Motome Yukitoshi , Tsunetsugu Hirokazu
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Microheterogeneous Solid Solutions in Perovskites: Formation, Microstructure, and Catalytic Activity
Authors: Isupova L. A. , Tsybulya S. V. , Kryukova G. N. , Rogov V. A. , Yakovleva I. S. , Sadykov V. A.
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Phosphapalladacycles: Forms of Existence and Reactions
Authors: Dunina V. V. , Gorunova O. N.
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Recent Advances in Siloxane‐Based Aryl—Aryl Coupling Reactions: Focus on Heteroaromatic Systems
Authors: Handy Christopher J. , Manoso Amy S. , McElroy William T. , Seganish W. Michael , DeShong Philip
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Chiral Recognition by Cyclodextrins — A General Mechanism
Authors: Kano Koji , Nishiyabu Ryuhei
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Applications of Sequential Three‐ and Four‐Component Reactions for Parallel Synthesis
Authors: Obrecht Daniel , Ermert Philipp
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Catalytic Enantioselective Cross‐Mannich Reaction of Aldehydes
Authors: Marques Maria Manuel B.
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Mollusk Shell Formation: A Source of New Concepts for Understanding Biomineralization Processes
Authors: Addadi Lia , Joester Derk , Nudelman Fabio , Weiner Steve
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Cytochrome c: Occurrence and Functions
Authors: Bertini Ivano , Cavallaro Gabriele , Rosato Antonio
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Recent Advances in Nonclassical Interligand Si×××H Interactions
Authors: Nikonov Georgii I.
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Design, Synthesis, and Pharmacological Characterization of Polyamine Toxin Derivatives: Potent Ligands for the Pore‐Forming Region of AMPA Receptors
Authors: Jensen Lars S. , Bølcho Ulrik , Egebjerg Jan , Strømgaard Kristian
Published: March 2006

Polyamine toxins, such as philanthotoxins, are low‐molecular‐weight compounds isolated from spiders and wasps, which modulate ligand‐gated ion channels in the nervous system. Philanthotoxins bind to the pore‐forming region of AMPA receptors, a subtype of glutamate receptors which are important for memory formation and are involved in neurodegenerative diseases. Previous studies have demonstrated that modification of the polyamine moiety of philanthotoxins can lead to very potent and highly selective ligands for the AMPA receptor, as exemplified with philanthotoxin‐56. Much less attention has been paid to the importance of the aromatic head group of philanthotoxins, but herein we demonstrate that modification of this moiety leads to a significant improvement in potency relative to philanthotoxin‐56 at cloned AMPA receptors. Interestingly, the incorporation of an adamantane moiety is particularly favorable, and the most potent compound has a Kivalue of 2 nM, making it the most potent uncompetitive antagonist of AMPA receptors described to date. Such compounds are potentially useful as neuroprotective agents.
Cover Picture: A PEG‐Based Biocompatible Block Catiomer with High Buffering Capacity for the Construction of Polyplex Micelles Showing Efficient Gene Transfer toward Primary Cells (ChemMedChem 4/2006)
Authors: Kanayama Naoki , Fukushima Shigeto , Nishiyama Nobuhiro , Itaka Keiji , Jang Woo‐Dong , Miyata Kanjiro , Yamasaki Yuichi , Chung Ung‐il , Kataoka Kazunori
Published: March 2006

The cover picture shows highly transfection‐efficient and less toxic polyplex micelles formed by the electrostatic interaction between DNA and block catiomers equipped with an ethylenediamine unit at the side chain. The catiomers undergo a conformational transition of the ethylenediamine unit from the gauche (mono‐protonated) to the anti (di‐protonated) form as the pH decreases from physiological to acidic conditions, providing a high buffering capacity for efficient transfection. The polyplex micelles showed effective and non‐cytotoxic transfection of a green fluorescent protein (GFP) gene into mouse primary osteoblast cells (background). For more details, see the full paper by N. Kanayama et al. on p. 439 ff.
Economic burden associated with breast cancer recurrence
Authors: Lamerato Lois , Havstad Suzanne , Gandhi Sanjay , Jones David , Nathanson David
Published: March 2006

BACKGROUND

The economics of breast cancer recurrence are poorly understood. For this retrospective cohort study, the authors evaluated the economic burden of breast cancer recurrence by using data from a large Midwestern healthcare system.

METHODS

Women with Stage I or II breast cancer (according to the American Joint Commission on Cancer staging criteria) were identified from the tumor registry of the Henry Ford Health System. The economic burden of breast cancer recurrence was estimated from patient charges (adjusted to 2003 U.S. dollars).

RESULTS

From 1996 to 2002, 1616 patients with early breast cancer were identified, including 192 patients who had recurrent tumors. Patients with recurrence had significantly greater charges in the 6‐month and 12‐month postrecurrence periods ($45,855 and $79,253, respectively) compared with the 6‐month and 12‐month prerecurrence periods ($10,715 and $12,344, respectively; both P <.001). This was evident for all recurrence types (locoregional, contralateral breast, and distant), but it was most evident for distant recurrences. In a regression analysis that was adjusted for baseline characteristics, the mean monthly charges were significantly greater for patients with recurrence versus patients without recurrence (P <.001), and this was true for each recurrence type. For women with recurrence (n = 74 patients), the mean charges during the 6‐month postrecurrence period were significantly greater than mean charges during the initial 6‐month period after diagnosis ($50,355 vs. $38,254; P <.01). Quarterly charges for continuing care postrecurrence were significantly greater than prerecurrence charges ($4934 vs. $1825; P <.001). The mean charges for terminal care were significantly greater (P <.01) for women with recurrence (n = 27 patients, $63,434) versus women without recurrence (n = 65 patients, $53,872).

CONCLUSIONS

Patients with early breast cancer who experienced recurrence required more costly care than patients who did not develop recurrent disease. Therapies that reduce the risk of recurrence may reduce costs significantly. Cancer 2006. © 2006 American Cancer Society.
Comparison of disruption procedures for enumeration of activated sludge floc bacteria by flow cytometry
Authors: Falcioni Tania , Manti Anita , Boi Paola , Canonico Barbara , Balsamo Maria , Papa Stefano
Published: March 2006

Background:

In a wastewater treatment plant, the degradation process is performed by a variable and mixed community of microorganisms in an aerobic aquatic environment. The activated‐sludge process is based on the formation of strong microbial flocs where many bacteria are attached to sludge flocs.

Methods:

Cytometric analysis requires an homogeneous cell suspension and so detachment of bacteria from flocs is required. In this study, sonication and homogenization were compared to find the most adequate pretreatment method for bacterial cytometric analysis in activated sludge samples. Bacterial viability was tested with a nucleic acid double‐staining (NADS) protocol (Barbesti et al., Cytometry 2000;40:214–218) and on flow cytometry.

Results:

Each method showed a good efficiency in terms of bacterial detachment; thus finally, the choice of which could be the best treatment method was based on both viability results and analysis rapidity. On the basis of the degree of cell detachment and viability, the maximum value was obtained by sonication (2 × 45″).

Conclusions:

The use of flow cytometry in conjunction with fluorescent dyes and an adequate pretreatment represents a useful method to rapidly detect and enumerate bacteria in activated sludge samples. © 2006 International Society for Analytical Cytology
Controversies in renal anemia management
Authors: Ifudu Onyekachi
Published: March 2006

Anemia plays a key role in generating excess cardiovascular morbidity and mortality in patients with chronic kidney disease. Among patients with end‐stage renal disease, low hemoglobin levels contribute to an increased rate of hospitalization and shortened survival.

Several issues in the pathogenesis and management of renal anemia, including the use of recombinant erythropoietin, are controversial and unresolved. In addition, the management of anemia has major economic implications. Clarifying these issues ultimately could enhance patient outcomes while lessening the need for erythropoietin and intravenous iron, which could potentially save millions of dollars.
Evaluating the effects of eating disorder memoirs on readers' eating attitudes and behaviors
Authors: Thomas Jennifer J. , Judge Abigail M. , Brownell Kelly D. , Vartanian Lenny R.
Published: March 2006

Objective:

More than 50 individuals have published eating disorder (ED) memoirs. The current study was the first to test whether memoirs affect readers' eating attitudes and behaviors, and whether they normalize and/or glamorize EDs.

Method:

Fifty female undergraduates read an ED or control memoir. Before and afterward, participants completed the 26‐item Eating Attitudes Test (EAT‐26), the Eating Disorders Inventory (EDI) Drive for Thinness subscale, a measure of perceived ED symptom prevalence, and an Implicit Association Test (IAT) measuring associations between anorexia and glamour/danger.

Results:

Participants in the ED condition did not demonstrate significant changes in the EAT‐26, the EDI Drive for Thinness subscale, perceived symptom prevalence, or IAT associations compared with controls. Before reading, the EAT‐26 and EDI Drive for Thinness subscale correlated positively with perceived symptom prevalence and strength of the IAT association between anorexia and glamour.

Conclusion:

ED memoirs appear to have little effect on undergraduates' eating attitudes and behaviors. Future research should investigate whether memoirs affect individuals with preexisting eating pathology, who may normalize and glamorize ED symptoms. © 2006 by Wiley Periodicals, Inc. Int J Eat Disord 2006
Induction of IgG antibodies against the GD2 carbohydrate tumor antigen by vaccination with peptide mimotopes
Authors: Riemer Angelika B. , Förster‐Waldl Elisabeth , Brämswig Kira H. , Pollak Arnold , Zielinski Christoph C. , Pehamberger Hubert , Lode Holger N. , Scheiner Otto , Jensen‐Jarolim Erika
Published: March 2006

The disialoganglioside GD2, a carbohydrate antigen, is expressed on all tumors of neuroectodermal origin, including melanoma, neuroblastoma, sarcoma and small cell lung cancer. Due to its specific expression on tumor surfaces, GD2 is an attractive target for immunotherapies. The mouse/human chimeric anti‐GD2 mAb ch14.18 is already applied in melanoma and neuroblastoma trials as a passive immunotherapy. To establish an active immunotherapy alternative, we aimed to replace the poorly immunogenic ganglioside with immunogenic peptides. Previously, we used the ch14.18 antibody to select GD2 peptide mimics from a phage display library. In the present study, two mimics of the ch14.18 epitope were coupled to keyhole limpet hemocyanin and used for immunizing BALB/c mice. Induction of a specific humoral immune response towards the original antigen GD2, both purified and expressed on neuroblastoma and melanoma cells, could be demonstrated in ELISA, Western blot, and immunofluorohistochemistry. As the elicited antibodies were of the IgG isotype, the mimotope conjugates were capable of recruiting T cell help and inducing memory phenomena. In conclusion, we show that an epitope of the carbohydrate antigen GD2 can successfully be translated into immunogenic peptide mimotopes. Our immunization experiments indicate that GD2 mimotopes are suitable for active immunotherapy of GD2‐expressing tumors.
The key regulators of adult T helper cell responses, STAT6 and T‐bet, are established in early life in mice
Authors: Rose Shawn , Guevara Patricia , Farach Sandra , Adkins Becky
Published: March 2006

Murine neonatal immunity is typically Th2 biased. This is characterized by high‐level IL‐4 production at all phases of the immune response and poor IFN‐γ memory responses. The differential expression of Th1/Th2 cytokines by neonates and adults could arise if the critical regulators of Th differentiation and function, STAT6 and T‐bet, operate differently during the neonatal period. To test this idea, the Th cell responses of wild‐type, T‐bet‐deficient, or STAT6‐deficient mice were compared in vitro and in vivo. The absence of these factors had similar qualitative effects on the development of effector function in neonates and adults, i.e., if a Th lineage was inhibited or enhanced in adult animals, a similar phenomenon was observed in neonates. However, there was a striking difference observed in the in vivo Th1 memory responses of STAT6‐deficient mice initially immunized as neonates. Antigen‐specific IFN‐γ production was increased 50–100‐fold in STAT6‐deficient neonates, achieving levels similar to those of STAT6‐deficient adults. These findings demonstrate that STAT6 and T‐bet signals are central in shaping Th responses in wild‐type neonates, as in adult mice, and that the master regulators of Th cell development and function are already firmly established in early life.
Tolls for B cells
Authors: Fillatreau Simon , Manz Rudolf A.
Published: March 2006

Priming of naive lymphocytes is important for yielding efficient immune responses. Mechanisms controlling this process are also important for preventing immune cells from attacking self‐antigens. It is well known that signals provided by innate immune receptors, such as Toll‐like receptors (TLR), are essential to induce dendritic cell maturation that subsequently allows the priming of naive T cells. In this issue of the European Journal of Immunology, it is shown that TLR stimulation effectively potentiates naive human B cell activation and production of antibodies in T‐dependent immune responses. TLR signals can be delivered to B cells directly, or indirectly via cytokines provided by TLR‐activated dendritic cells.

See accompanying article http://www.dx.doi.org/10.1002/eji.200535744
Perceptions of social influence when messages favour ‘us’ versus ‘them’: A closer look at the social distance effect
Authors: Elder Tracey J. , Douglas Karen M. , Sutton Robbie M.
Published: March 2006

The third‐person effect (TPE) is the tendency for individuals to assume that persuasive communications have a stronger effect on other people than on themselves. In turn the social distance effect (SDE) is the tendency for this TPE to increase with the psychological distance between self and comparator. Two experiments showed that the SDE is moderated by whether the message favours the ingroup or the outgroup, holding all other content constant. In Study 1, male and female participants read a message arguing that either women were better drivers than men or vice versa, and then indicated how much they thought themselves, ingroup members, outgroup members and society would be influenced. The results indicate that for the pro‐outgroup message the SDE was found. However, for the pro‐ingroup message the SDE was reversed with ingroup members perceived as more influenced than all other targets, including the self. Study 2 replicated this finding using minimal groups, which eliminated the effects of prior stereotypes about male and female drivers. Across both studies the self was perceived as relatively invulnerable to influence regardless of message bias. Copyright © 2006 John Wiley & Sons, Ltd.
Counterion‐dye staining for DNA in electrophoresed gels using indoine blue and methyl orange
Authors: Hwang Sun‐Young , Jin Li‐Tai , Yoo Gyurng‐Soo , Choi Jung‐Kap
Published: March 2006

In this study, we describe a sensitive staining method for DNA in agarose and polyacrylamide gels using organic visible dyes, indoine blue (IB) and methyl orange (MO). The counterion‐dye staining method uses two oppositely charged dyes to form a hydrophobic ion pair complex in the staining solution. A decrease in the number of free forms of dyes in staining solution can enhance the selectivity of binding between the dye and DNA, and can reduce nonspecific background staining. As a result, the sensitivity of counterion‐dye staining was significantly improved compared with other dye‐based staining. This method uses a staining solution consisting of 0.008% IB, 0.002% MO, 10% ethanol and 0.2 M sodium acetate at pH 4.7, and can detect 5 ng of λ DNA/HindIII within 60 min in agarose gels and 10 ng of ΦX174 DNA/HaeIII within 20 min in polyacrylamide gels.
Digital switchover in UHF: the ATHENA concept for broadband access
Authors: Pallis Evangelos , Mantakas Charalambos , Mastorakis George , Kourtis Anastasios , Zacharopoulos Vassilios
Published: March 2006

This paper presents a concept adopted by ATHENA IST‐507312 project for the proper adoption of digital switchover (DSO) in UHF, towards establishing broadband access especially in rural and less favoured regions. Taking into account the local and networking capabilities of terrestrial digital video broadcasting standard (DVB‐T), and by building on three pillars (a) the regenerative DVB‐T concept, (b) the backhaul configurations and (c) the ‘bit‐rate allocation’ aspect rather than the ‘frequency allocation’ one, it designs, implements and validates a broadband Fusion environment, which is capable of enabling access not only to digital TV bouquets, but also and most predominant to Information Society services, such as Internet, e‐mail, multimedia on demand etc. within the same stream. Citizens access them via intermediate distribution nodes, namely cell main nodes (CMNs). Such a Fusion environment is commonly shared among broadcasters, telecom operators and active users/citizens, for open competition in technological and service level, in content creation and delivery level, in networking business/market field. Finally, the paper elaborates on the potentialities of the DSO in UHF to provide not only digital TV bouquets, but also a broadband access Fusion environment in regional level. Copyright © 2006 AEIT.
Modelling of a PEM Fuel Cell System with Propane ATR Reforming
Authors: Liu Z. , Mao Z. , Xu J. , Hess‐Mohr N. , Schmidt V. M.
Published: March 2006

Proton exchange membrane fuel cells (PEMFCs) are promising power sources not only for electric vehicles, but also for portable and stationary applications. In this paper, a 5 kW PEMFC system, suggested for domestic power applications with propane autothermal reforming, is modelled with PRO/II® from SIMSCI. When the fuel cell is operated at 2 atm, 80 °C, a hydrogen conversion of 0.75 and at an air stoichiometry 3.0, with the energies of the compressor and expander coupled with a 75% adiabatic efficiency, the system efficiency is calculated to be 34.8%. Different operating pressures and temperatures are studied; lower system efficiency is shown at higher pressure, lower temperature, and greater air stoichiometry. The simulation shows a significant drop in system efficiency for a lowered compressor and expander adiabatic efficiency. With an increase in this value from 50% to 85%, the system efficiency increases from 23.1% to 40.6%. The simulation reveals that it is critical to design special compressors and expanders for fuel cells with higher adiabatic efficiencies so that higher system efficiency can be achieved.
5‐fluorouracil‐related gene expression levels in primary colorectal cancer and corresponding liver metastasis
Authors: Kuramochi Hidekazu , Hayashi Kazuhiko , Uchida Kazumi , Miyakura Satoru , Shimizu Daisuke , Vallbohmer Daniel , Park Seongjin , Danenberg Kathleen D. , Takasaki Ken , Danenberg Peter V.
Published: March 2006

Gene expression levels of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP) and orotate phosphoribosyl transferase (OPRT) have been shown to be associated with response to 5‐fluorouracil‐based therapies. Analyzing these gene expression levels in liver metastases is important to obtain the best prediction of therapy. Our aim was to determine how TS, DPD, TP and OPRT gene expression levels in primary colorectal cancer (CRC) were related to those in liver metastases. Formalin‐fixed, paraffin‐embedded tumor specimens from 31 pairs of primary CRC and corresponding liver metastases were dissected by using laser‐captured microdissection. RNA was extracted and cDNA was prepared by reverse‐transcription. Quantitation of target gene and internal reference gene was performed using real‐time PCR. No significant difference was seen between median mRNA expression levels of TS, DPD, TP and OPRT in primary cancer and those in corresponding liver metastases (median value: TS 1.48 vs. 1.43; p = 0.92, DPD 0.19 vs.0.12; p = 0.10, TP 1.20 vs. 0.98; p = 0.39, OPRT 1.17 vs. 0.95; p = 0.10). When matched tissue sets were compared on an individual basis, there was a significant correlation for TS mRNA expression between primary cancer and corresponding liver metastases (rs = 0.52, p = 0.0026). However, no correlation was seen between matched sets for DPD, TP or OPRT. Significant correlation was seen between DPD and TP expression levels in both primary CRC (rs = 0.38, p = 0.03) and liver metastases (rs = 0.72, p < 0.0001). A good prediction of TS mRNA levels in liver metastases can be obtained by measuring those of primary CRC, although no correlation was seen for DPD, TP and OPRT. © 2006 Wiley‐Liss, Inc.
4‐HPR modulates gene expression in ovarian cells
Authors: Brewer Molly , Kirkpatrick Nathaniel D. , Wharton J. Taylor , Wang Jian , Hatch Kenneth , Auersperg Nelly , Utzinger Urs , Gershenson David , Bast Robert , Zou Changping
Published: March 2006

Ovarian cancer has a high rate of recurrence and subsequent mortality following chemotherapy despite intense efforts to improve treatment outcomes. Recent trials have suggested that retinoids, especially 4‐(N‐hydroxyphenyl) retinamide (4‐HPR), play an important role as a chemopreventive agent and are currently being used in clinical trials for ovarian cancer chemoprevention as well as treatment. This study examines the mechanism of its activity in premalignant and cancer cells. We investigated the modulation of gene expression by 4‐HPR in immortalized ovarian surface epithelial (IOSE) cells and ovarian cancer (OVCA433) cells with DNA microarray. Real time RT‐PCR and western blotting were used to confirm the microarray results and metabolic changes were examined with optical fluorescence spectroscopy. 4‐HPR resulted in an up‐regulation of expression of proapoptotic genes and mitochondrial uncoupling protein in OVCA433 cells and modulation of the RXR receptors in IOSE cells, and down‐regulation of mutant BRCA genes in both IOSE and OVCA433 cells. 4‐HPR had a larger effect on the redox in the 433 cells compared to IOSE. These findings suggest that 4‐HPR acts through different mechanisms in premalignant ovarian surface cells and cancer cells, with a preventive effect in premalignant cells and a treatment effect in cancer cells. © 2006 Wiley‐Liss, Inc.
In‐vivo measurements of the dielectric properties of breast carcinoma xenografted on nude mice
Authors: Cho Jeiwon , Yoon Jeonghoon , Cho Sungjoon , Kwon Kihyun , Lim Sungkyu , Kim Daeduk , Lee Eun Sook , Kim Chul Hwan , Choi Jin Wook , Cheon Changyul , Kwon Youngwoo
Published: March 2006

A developing method of cancer detection is to use electromagnetic waves to compare the dielectric properties of normal and cancerous tissue. Because most of the previous studies consisted of dielectric measurements taken ex‐vivo, this study investigated the advantages of in‐vivo measurements, obtained using the newly developed insertion‐type planar probe, through the measurements of cancer (MDA MB 231), which was cultivated and implanted into the mammary fat pad of nude mice. Reflection coefficients were obtained in the broadband frequency range from 0.5 to 30 GHz, from which broadband complex permittivity data was extracted. Complex permittivity, in addition to other parameters such as conductivity and characteristic frequency, were used to make comparisons between cancerous tissue, normal muscle tissue and fat tissue, as well as comparisons between in‐vivo and ex‐vivo measurements. This study investigated the suitability of in‐vivo cancer detection using microwaves with the newly developed insertion‐type planar probe. Results showed that both sensitivity and specificity of the current method was 97%. In addition, predictive values were 99% for the positive and 94% for the negative, thus greatly enhancing the practicality of this method. In conclusion, it was demonstrated that in‐vivo measurements are highly beneficial in studying the potential of microwaves as a diagnostic tool of breast cancer, especially in combination with the newly developed insertion‐type planar probe. © 2006 Wiley‐Liss, Inc.
Familial risks of esophageal cancer among the Turkmen population of the Caspian littoral of Iran
Authors: Akbari Mohammad Reza , Malekzadeh Reza , Nasrollahzadeh Dariush , Amanian Dayan , Sun Ping , Islami Farhad , Sotoudeh Masoud , Semnani Shahriar , Boffeta Paolo , Dawsey Sanford M. , Ghadirian Parviz , Narod Steven A.
Published: March 2006

In northeastern Iran, there is an area of high incidence of esophageal cancer, which is populated by residents of Turkmen ancestry. Several environmental risk factors for esophageal cancer have been proposed, but the roles of familial and genetic factors have not been studied extensively in the Turkmen population. We evaluated the importance of familial risk factors for esophageal cancer by performing a case–control study of 167 cases of esophageal squamous cell carcinoma and 200 controls of Turkmen ethnicity. Detailed family pedigrees of the cases and controls were constructed, which documented all cancers in first‐ and second‐degree relatives. The actuarial risk of cancer was then estimated in 2,097 first‐degree relatives of cases and 2,783 first‐degree relatives of the controls. A hazard ratio was constructed, based on a comparison of the 2 cumulative incidence curves. The risk to age 75 of esophageal cancer in the first‐degree relatives of Turkmen patients with esophageal cancer was 34% versus 14% for the first‐degree relatives of the controls (hazard ratio = 2.3; p = 3 × 10−8). Cases (9.6%) reported that their parents were related, versus 2.5% of the controls who reported this. (odds ratio = 4.1; p value = 0.006). Familial factors are important in the etiology of esophageal cancer among the Turkmen residents of Iran. The hazard ratio of 2.3 for cancer among first‐degree relatives is consistent with an important contribution of heritable factors. It will be of interest to perform marker studies to establish which genes are responsible. © 2006 Wiley‐Liss, Inc.
Inhibitors of the PI3‐kinase/Akt pathway induce mitotic catastrophe in non‐small cell lung cancer cells
Authors: Hemström Therese H , Sandström Margareta , Zhivotovsky Boris
Published: March 2006

Non‐small cell lung cancer cells (NSCLC) are more resistant to anticancer treatment as compared with other types of cancer cells. Recently (Hemström et al., Exp Cell Res 2005;305:200–13) we showed that apoptosis of U1810 NSCLC cells induced by the staurosporine analog PKC 412 correlated with inhibition of Akt and ERK1/2, suggesting the involvement of these kinases in cell survival. Here we investigated the contribution of the PI3‐kinase/Akt and MEK/ERK pathways to survival of NSCLC cells. The two signaling pathways were studied by using different combinations of the PI3‐kinase inhibitors LY‐294002 and wortmannin, the Akt activator Ro 31‐8220, the MEK inhibitor PD 98059 and PKC 412. PI3‐kinase inhibitors induced apoptosis‐like death in U1810 cells. H157 cells in general were relatively resistant to PI3 kinase/Akt inhibitors yet these compounds sensitized cells to the DNA‐damaging drug VP‐16, while Ro 31‐8220 could not. PD 98059 only had a sensitizing effect on H157 cells when combined with PI3‐kinase inhibition and VP‐16. Morphological data indicated that LY‐294002 and PKC 412 induced cell death at anaphase and metaphase, respectively, suggesting death by mitotic catastrophe. Analyzes of cells blocked in G2/M‐phase by nocodazol revealed that LY‐294002 increased, while PKC 412 decreased histone H3 phosphorylation, suggesting that LY‐294002 allowed, while PKC 412 inhibited cells to leave M‐phase. Flow cytometric analysis of cell cycle distribution demonstrated that LY‐294002 allowed cells to leave G2/M phase, while PKC 412 inhibited cytokinesis, resulting in formation of multinucleated cells. These results indicate that sensitization of NSCLC cells by PI3‐kinase inhibition involves interplay between cell cycle regulation, mitotic catastrophe and apoptosis. © 2006 Wiley‐Liss, Inc.
The characterization of the invasion phenotype of uveal melanoma tumour cells shows the presence of MUC18 and HMG‐1 metastasis markers and leads to the identification of DJ‐1 as a potential serum biomarker
Authors: Pardo María , García Ángel , Thomas Benjamin , Piñeiro Antonio , Akoulitchev Alexandre , Dwek Raymond A. , Zitzmann Nicole
Published: March 2006

Uveal malignant melanoma (UM) is the most frequent primary intraocular tumour in adult humans. Because the survival rate of patients with UM has changed little in the past few decades, a better understanding of the molecular events governing UM development and the identification of markers indicating the potential for metastasis at the time of diagnosis are necessary to design improved and more specific treatments. In this study, we investigated UM tumour development by comparing two recently established UM cultures with different invasion potential by two‐dimensional gel electrophoresis. Protein features expressed differentially were identified by mass spectrometric analysis. Potential markers were assayed in both cultures and in long‐term established UM cell lines (UW‐1, OCM‐1, SP6.5 and 92.1) by Western blotting and their role in invasion analysed using Matrigel membranes. Comparative analysis revealed that UM cultures with low‐ and high‐grade invasion potential differ in their cellular metabolism and, more interestingly, in several cancer‐associated proteins, including those implicated in cell adhesion and migration, proliferation and various oncogenes. Our data indicate a correlation between MUC18 and HMG‐1 expression and the invasiveness of UM cells. We also demonstrate the expression and secretion of DJ‐1 oncoprotein by UM cells. We suggest a possible role for MUC18 and HMG‐1 proteins in UM cell invasion. The secretion of DJ‐1 by UM cells, and the ability to detect this protein in UM patients' sera implicate it as a potential noninvasive biomarker for this malignancy. © 2006 Wiley‐Liss, Inc.
SH‐7, a new synthesized shikonin derivative, exerting its potent antitumor activities as a topoisomerase inhibitor
Authors: Yang Fan , Chen Yi , Duan Wenhu , Zhang Chao , Zhu Hong , Ding Jian
Published: March 2006

1‐(1,4‐dihydro‐5,8‐dihydroxy‐1,4‐dioxonaphthalen‐2‐yl)‐4‐methylpent‐3‐enylfuran‐2‐caroxylate (SH‐7), a new naphthoquinone compound, derived from shikonin, exhibited obvious inhibitory actions on topoisomerase II (Topo II) and topoisomerase I (Topo I), which were stronger than its mother compound shikonin. Notably, the SH‐7's inhibitory potency on Topo II was much stronger than that on Topo I. In addition, SH‐7 significantly stabilized Topo II‐DNA cleavable complex and elevated the expression of phosphorylated‐H2AX. The in vitro cell‐based investigation demonstrated that SH‐7 displayed wide cytotoxicity in diversified cancer cell lines with the mean IC50 value of 7.75 μM. One important finding is SH‐7 displayed significant cytotoxicity in the 3 MDR cell lines, with an average IC50 value nearly equivalent to that of the corresponding parental cell lines. The average resistance factor (RF) of SH‐7 was 1.74, which was much lower than those of reference drugs VP‐16 (RF 145.92), ADR (RF 105.97) and VCR (RF 197.39). Further studies illustrated that SH‐7 had the marked apoptosis‐inducing function on leukemia HL‐60 cells, which was validated to be of mitochondria‐dependence. The in vivo experiments showed that SH‐7 had inhibitory effects on S‐180 sarcoma implanted to mice, SMMC‐7721, BEL‐7402 human hepatocellular carcinoma and PC‐3 human prostate cancer implanted to nude mice. Taken together, these results suggest that SH‐7 induces DSBs as a Topo II inhibitor, which was crucial to activate the apoptotic process, and subsequently accounts for its both in vitro and in vivo antitumor activities. The well‐defined Topo II inhibitory activity, antitumor effects particularly with its obvious anti‐MDR action, better solubility and less toxicity make SH‐7 as a potential antitumor drug candidate for further research and development. © 2006 Wiley‐Liss, Inc.
Determination of viral load thresholds in cervical scrapings to rule out CIN 3 in HPV 16, 18, 31 and 33‐positive women with normal cytology
Authors: Snijders Peter J.F. , Hogewoning Cornelis J.A. , Hesselink Albertus T. , Berkhof Johannes , Voorhorst Feja J. , Bleeker Maaike C.G. , Meijer Chris J.L.M.
Published: March 2006

An increased high‐risk human papillomavirus (hrHPV) viral load in cervical scrapings has been proposed as a determinant for high‐grade cervical intraepithelial neoplasia (CIN) and cervical cancer (≥CIN 2), but data so far for HPV types different from HPV 16 are limited and inconsistent. In addition, a viral load threshold to distinguish hrHPV positive women without ≥CIN 2 still has not been defined. Here, we used baseline cervical scrapings of women with normal cytology participating in a large population‐based cervical screening trial (i.e. POBASCAM) who were GP5+/6+‐PCR positive for 4 common hrHPV types, i.e. HPV 16, 18, 31 or 33, as a reference to arbitrarily define various viral load thresholds (i.e. 25th, 33rd, 50th, 67th and 75th percentiles of the lowest viral load values) for distinguishing women having single infections with these types without high‐grade CIN. Viral load assessment was performed by real time type‐specific PCR. The viral load threshold values were subsequently validated on abnormal cervical scrapes of 162 women with underlying, histologically confirmed CIN lesions containing 1 of these 4 hrHPV types. All 59 women with CIN 3 had viral load levels that were higher than those of 33% of the women with normal cytology containing the respective hrHPV type detectable by GP5+/6+‐PCR (i.e. higher than the 33rd percentile of viral load). By using this 33rd percentile viral load cut‐off, sensitivity for CIN 3 of 100% (95% CI 93.9–100) was obtained. Hence, application of this viral load threshold would increase the specificity of HPV testing for HPV 16, 18, 31 and 33‐associated prevalent CIN 3 without the cost of a marked reduction in sensitivity. In practice, on the basis of viral load analysis, a less aggressive management can be foreseen for 33% of the women with normal cytology participating in a population‐based screening program who are GP5+/6+‐PCR positive for HPV 16, 18, 31 or 33. © 2006 Wiley‐Liss, Inc.
Chromosome 9 deletions are more frequent than FGFR3 mutations in flat urothelial hyperplasias of the bladder
Authors: van Oers Johanna M.M. , Adam Christoph , Denzinger Stefan , Stoehr Robert , Bertz Simone , Zaak Dirk , Stief Christian , Hofstaedter Ferdinand , Zwarthoff Ellen C. , van der Kwast Theodorus H. , Knuechel Ruth , Hartmann Arndt
Published: March 2006

Flat urothelial hyperplasias (FUHs) in patients with papillary bladder tumours frequently show deletions of chromosome 9, suggesting that FUH could be the first neoplastic step in the development of papillary bladder cancer. FGFR3 mutations are frequent in non‐invasive papillary tumours with low risk of progression. Our aim was to investigate the frequency of FGFR3 mutations and deletions of chromosomes 9p/q and 8p/q in FUH. Thirty FUH and 9 simultaneous or consecutive tumours were detected by 5‐ALA‐based photodynamic cystoscopy. DNA was isolated from frozen sections and whole genome amplification was done by I‐PEP‐PCR, followed by LOH analysis on chromosomes 8p/q and 9p/q. FGFR3 mutations were detected by SNaPshot analysis. LOH analysis on FUH revealed deletions at 9p/q (11/30, 37%) and 8p/q (3/30, 10%). FGFR3 mutations were found in 7/30 FUH (23%). Only 2 FUH showed an FGFR3 mutation without deletions of chromosome 9. In contrast, 6 FUH revealed chromosome 9 deletions but wild type FGFR3 (p = 0.03). These results suggest that chromosome 9 deletions are the earliest genetic alterations in bladder cancer. The detection of FGFR3 mutations in FUH further supports the role of this lesion as precursor of papillary bladder cancer. © 2006 Wiley‐Liss, Inc.
Anti‐tumor efficacy of a transcriptional replication‐competent adenovirus, Ad‐OC‐E1a, for osteosarcoma pulmonary metastasis
Authors: Li Xiong , Jung Chaeyong , Liu You‐Hong , Bae Kyung‐hee , Zhang Yan‐Ping , Zhang Hong‐Ji , VanderPutten Dale , Jeng Meei‐Huey , Gardner Thomas A. , Kao Chinghai
Published: March 2006

Background

Osteosarcoma (OSA) is the most frequent type of primary malignant bone tumor and is apt to occur in children and young adults. Pulmonary metastasis (OSPM) is the major reason for its fatal outcome. Osteocalcin (OC) is a major noncollagenous bone protein whose expression is limited almost exclusively to bone marrow and osteotropic tumors. OC is also known to express in cell lines with bone metastasis feathers. Gene therapy strategies with the OC promoter directing the replication of adenovirus in a tumor‐specific manner are a potential modality for OSPM therapy.

Methods

We detected OC mRNA expression by RNA in situ hybridization in OSA and OSPM samples from patients, and tested OC promoter transcriptional activity in OSA and non‐OSA cell lines. Then we used a transcriptional replication‐competent adenovirus, Ad‐OC‐E1a, to treat OSPM, and evaluated its tumor‐specific replication and killing activities in vitro as well as anti‐OSPM efficacy in vivo via systemic delivery.

Results

OC mRNA was detected in all types of OSA tissues, including OSPM tissues. The transcriptional activity of the OC promoter was much higher in a OSPM cell line SAOS‐2LM7 and primary OSA cell line MG63 than in non‐OSA cell lines, including cell lines from breast cancer, colon cancer, and liver cancer. Ad‐OC‐E1a expressed E1a protein only in MG63 and SAOS‐2LM7, which indicated that adenovirus E1a was under strict control by the OC promoter. Ad‐OC‐E1a demonstrated killing and viral replication activity close to wild‐type adenovirus levels in MG63 and SAOS‐2LM7, but the killing and viral replication activities were attenuated significantly in cells expressing low OC transcriptional activity. To test whether Ad‐OC‐E1a could be used to target human OSPM in vivo, SAOS‐2LM7 pulmonary metastasis models in nude mice were induced and treated by tail‐vein injection with Ad‐OC‐E1a. Compared to tumor nodules in the lung in groups treated with PBS or control virus, the quantity of metastasized tumor nodules decreased significantly. Adenovirus‐infected cells were stained immunohistochemically only inside and around the OSPM nodules but spared normal lung tissue and other organs.

Conclusions

These data demonstrated that OC promoter could direct adenovirus replication by controlling the E1a gene to target human OSPM in a tumor‐specific manner, providing an efficient tool to develop a feasible therapeutic modality for OSPM. Copyright © 2006 John Wiley & Sons, Ltd.
Tendon and neurovascular bundle displacement in the palm with hand flexion and extension: An MRI and gross anatomy correlative study
Authors: Canuto Holly C. , Oliveira Miguel L.R. , Fishbein Kenneth W. , Spencer Richard G.
Published: March 2006

This study evaluated the correlative use of MRI methods and gross anatomy to monitor tendon displacement in the central region of the palm at rest and during flexion and extension of the metacarpophalangeal and interphalangeal joints with respect to the corresponding neurovascular bundles (NVBs). In all of the samples the neutral and extended positions showed the NVB to be palmar with respect to the flexor tendons, while during flexion tendon displacement caused the NVB to be dorsal to both the flexor digitorum superficialis (FDS) and flexor digitorum profundus (FDP) tendons. T1‐weighted MR images correlated with gross anatomical slides demonstrated that significant changes occur in the relative positions of the flexor tendons and associated NVBs of the palm upon flexion and extension. J. Magn. Reson. Imaging 2006. Published 2006 Wiley‐Liss, Inc.