bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery of Adamantyl Ethanone Derivatives as Potent 11β‐Hydroxysteroid Dehydrogenase Type 1 (11β‐HSD1) Inhibitors
Authors: Su Xiangdong , Pradaux‐Caggiano Fabienne , Thomas Mark P. , Szeto Michelle W. Y. , Halem Heather A. , Culler Michael D. , Vicker Nigel , Potter Barry V. L.
Published: May 2010

11β‐Hydroxysteroid dehydrogenases (11β‐HSDs) are key enzymes regulating the pre‐receptor metabolism of glucocorticoid hormones. The modulation of 11β‐HSD type 1 activity with selective inhibitors has beneficial effects on various conditions including insulin resistance, dyslipidemia and obesity. Inhibition of tissue‐specific glucocorticoid action by regulating 11β‐HSD1 constitutes a promising treatment for metabolic and cardiovascular diseases. A series of novel adamantyl ethanone compounds was identified as potent inhibitors of human 11β‐HSD1. The most active compounds identified (52, 62, 72, 92, 103 and 104) display potent inhibition of 11β‐HSD1 with IC50 values in the 50–70 nM range. Compound 72 also proved to be metabolically stable when incubated with human liver microsomes. Furthermore, compound 72 showed very weak inhibitory activity for human cytochrome P450 enzymes and is therefore a candidate for in vivo studies. Comparison of the publicly available X‐ray crystal structures of human 11β‐HSD1 led to docking studies of the potent compounds, revealing how these molecules may interact with the enzyme and cofactor.
NMR‐Guided Molecular Docking of a Protein–Peptide Complex Based on Ant Colony Optimization
Authors: Korb Oliver , Möller Heiko M. , Exner Thomas E.
Published: May 2010

Standard docking approaches used for the prediction of protein–ligand complexes in the drug development process have problems identifying the correct binding mode of large flexible ligands. Herein we show how additional experimental data from NMR experiments can be used to predict the binding mode of a mucin 1 (MUC‐1) pentapeptide recognized by the breast‐cancer‐selective monoclonal antibody SM3. Distance constraints derived from trNOE and saturation transfer difference NMR experiments are combined with the docking approach PLANTS. The resulting complex structures show excellent agreement with the NMR data and with a published X‐ray crystal structure. The method was then further tested on two complexes in order to demonstrate its more general applicability: T‐antigen disaccharide bound to Maclura pomifera agglutinin, and the inhibitor SBi279 bound to S100B protein. Our new approach has the advantages of being fully automatic, rapid, and unbiased; moreover, it is based on relatively easily obtainable experimental data and can greatly increase the reliability of the generated structures.
Towards MRI contrast agents responsive to Ca(II) and Mg(II) ions: metal‐induced oligomerization of dota–bisphosphonate conjugates
Authors: Kubíček Vojtěch , Vitha Tomáš , Kotek Jan , Hermann Petr , Vander Elst Luce , Muller Robert N. , Lukeš Ivan , Peters Joop A.
Published: May 2010

In magnetic resonance imaging (MRI), paramagnetic complexes are utilized as contrast agents. Much attention has been paid to the development of new contrast agents responsive to pH, temperature or concentration of various components of body liquids. We report a new type of MRI probe sensing the concentrations of calcium and magnesium in biological media. The ligand do3apBP combines a dota‐like chelator with a bisphosphonate group. In the complex, the Gd(III) ion is entrapped in the macrocyclic cavity whereas the bisphosphonate group is not coordinated and therefore is available for coordination with endogenous metal ions. In the presence of metal ions, Gd–do3apBP appears to show formation of coordination oligomers leading to an unprecedented increase in r1 up to 200–500%. The extremely high relaxivity response makes this type of compound interesting for further studies as MRI ion‐responsive probes for biomedical research. Copyright © 2010 John Wiley & Sons, Ltd.
NMR relaxation and magnetic properties of superparamagnetic nanoworms
Authors: Gossuin Yves , Disch Sabrina , Vuong Quoc L. , Gillis Pierre , Hermann Raphaël P. , Park Ji‐Ho , Sailor Michael J.
Published: May 2010

Maghemite particles are used as T2 contrast agents for magnetic resonance imaging, especially for molecular and cellular imaging. Linear clusters of particles – called nanoworms – were recently developed to enhance the targeting efficiency. In this work, the magnetic and NMR relaxation properties of these nanoworms are studied at multiple magnetic fields. After the usual saturation at 0.5 T, the magnetization of the worms is still increasing, which results in an appreciable increase of the transverse relaxivity at high magnetic fields. The obtained relaxivities are typical of superparamagnetic particles of iron oxide (SPIOs). The transverse relaxation of the worms is clearly more efficient than for the isolated grains, which is confirmed by computer simulations. At high field, the longitudinal relaxation of the worms is less pronounced than for the grains, as expected for SPIOs. The nanoworms thus constitute a promising T2 agent for cellular and molecular imaging. Copyright © 2010 John Wiley & Sons, Ltd.
Inflammatory breast cancer in Italy
Authors: Ionta Maria Teresa , Atzori Francesco , Massidda Bruno
Published: May 2010

Breast cancer represents the most common cancer among women in Italy. In the last decade, an increase in incidence and a decrease in mortality from breast cancer have been observed in Italy. These findings may be explained at least in part by the implementation of organized screening programs (SMPs). The screening programs are not diffused homogeneously throughout Italy, where approximately 60% of the population in covered, which explains in part the different outcomes observed across Italy. On the basis of the available data, the authors of this report performed a retrospective analysis on the incidence of 2 different groups of breast cancer patients: those covered or and those not covered by SMPs in Italy. The rates of incidence of T4a, T4b, and T4c breast cancer and of T4 inflammatory breast cancer (IBC) overtime appeared to be lower for the population that was covered by SMPs. On the basis of the estimated 40,000 new cases of breast cancer in Italy per year, the authors attempted to extrapolate the approximate incidence of new cases of T4 breast cancer and calculated that there were between 2800 and 3600 new cases per year taking into account the differences in incidence observed in areas covered or not covered by SMPs. Following the same extrapolations, the estimated incidence of IBC was approximately 200 to 800 new cases per year, representing from 0.6% to 2% of all breast cancers diagnosed every year in Italy. Cancer 2010;116(11 suppl):2736–40. © 2010 American Cancer Society.
Gene expression profiling of inflammatory breast cancer
Authors: Bertucci François , Finetti Pascal , Birnbaum Daniel , Viens Patrice
Published: May 2010

BACKGROUND:

Inflammatory breast cancer (IBC) is a rare but aggressive form of breast cancer. Despite multimodality treatment, the long‐term survival rate for patients with IBC has remained inferior at 50%. Until recently, IBC was understudied at the molecular level. Since 2004, new high‐throughput molecular profiling technologies have been applied to clinical samples with the aim of identifying genes or pathways potentially involved in disease development that may represent new, clinically relevant targets.

METHODS:

The authors conducted gene expression profiling studies of IBC clinical samples and investigated issues that may be addressed in the future to allow the “omics” approach to reach its full potential in IBC.

RESULTS:

Starting in December 2004, 6 research groups compared the expression profiles of IBC samples and non‐IBC samples. The series of samples were small (37 IBCs for the largest study) and heterogeneous (various tumor selection criteria and technologic platforms were used). The results indicated the feasibility of messenger RNA expression profiling from IBC biopsies, and they demonstrated the great transcriptional heterogeneity of IBC and the existence of molecular subtypes similar to non‐IBC that more frequently were basal and positive for ERBB2. Supervised analyses demonstrated differences in gene expression levels between the IBC and non‐IBC variable across studies with sometimes no or very subtle differences and, to date, no gene overlap across the reported signatures. No signature predictive of therapeutic response or clinical outcome has been reliably identified or validated.

CONCLUSIONS:

Because of the great heterogeneity of IBC, future studies will have to include larger series of IBC samples that are selected using homogeneous criteria. This calls for urgent international collaborations. Cancer 2010;116(11 suppl):2783–93. © 2010 American Cancer Society.
Angiogenesis, lymphangiogenesis, growth pattern, and tumor emboli in inflammatory breast cancer
Authors: Vermeulen Peter B. , van Golen Kenneth L. , Dirix Luc Y.
Published: May 2010

This objective of the current review was to provide the reader with a comprehensive summary of the literature related to 3 important and inter‐related features of the biology of inflammatory breast cancer (IBC): angiogenesis, lymphangiogenesis, and the formation of tumor emboli. Information derived from animal models of IBC as well as from translational studies using tissue samples of patients with IBC are discussed. Cancer 2010;116(11 suppl):2748–54. © 2010 American Cancer Society.
Overcoming radiation resistance in inflammatory breast cancer
Authors: Woodward Wendy A. , Debeb Bisrat G. , Xu Wei , Buchholz Thomas A.
Published: May 2010

The clinical‐pathological features of inflammatory breast cancer include enrichment of factors that have been previously associated with radioresistant disease, including negative hormone receptor status and a phenotype enriched for relatively radioresistant breast cancer stem/progenitor cells. The risks and benefits of accelerated postmastectomy radiation treatment regimens in the multimodality management of inflammatory breast cancer were reviewed at the first International Inflammatory Breast Cancer Conference at The University of Texas M. D. Anderson Cancer Center. The biological basis for radiation resistance and strategies to radiosensitize these tumors were also presented. The prevalent basal phenotype of inflammatory breast cancer makes it an ideal clinical model to examine stem cell hypotheses, which the authors believe can help guide future trials to continue making incremental progress against this aggressive disease. Cancer 2010;116(11 suppl):2840–5. © 2010 American Cancer Society.
Characterization of the roles of RHOC and RHOA GTPases in invasion, motility, and matrix adhesion in inflammatory and aggressive breast cancers
Authors: Wu Mei , Wu Zhi‐fen , Rosenthal Devin T. , Rhee Elliot M. , Merajver Sofia D.
Published: May 2010

BACKGROUND:

The 2 closely related small GTPases, RHOC and RHOA, are involved in mammary gland carcinogenesis; however, their specific roles in determining cancer cell adhesion and invasion have not been elucidated.

METHODS:

RHOA and RHOC are highly homologous, thereby posing a major challenge to study their individual functions in cancer cells. By selectively knocking down these proteins, we have been able to alternatively inhibit RHOC and RHOA, while preserving expression of the other rho protein. Quantitative analyses of the growth patterns and invasion in the aggressive estrogen receptor negative cell lines MDA‐231 and SUM149 were carried out on collagen I and Matrigel substrates.

RESULTS:

RHOC, and not RHOA, modulates surface expression and colocalization of α2 and β1 integrins in MDA‐MB‐231 on collagen I. Neither RHOC or RHOA affected integrin expression in the inflammatory breast cancer cell line SUM149, further highlighting the different regulation of adhesion and motility in inflammatory breast cancer.

CONCLUSIONS:

This work shows that RHOC and RHOA play different roles in cell‐matrix adhesion, motility, and invasion of MDA‐MB‐231 and reaffirms the crucial role of RHOC‐GTPase in inflammatory breast cancer cell invasion. Cancer 2010;116(11 suppl):2768–82. © 2010 American Cancer Society.
Vanishing viscosity limit of the Navier‐Stokes equations to the euler equations for compressible fluid flow
Authors: Chen Gui‐Qiang G. , Perepelitsa Mikhail
Published: May 2010

We establish the vanishing viscosity limit of the Navier‐Stokes equations to the isentropic Euler equations for one‐dimensional compressible fluid flow. For the Navier‐Stokes equations, there exist no natural invariant regions for the equations with the real physical viscosity term so that the uniform sup‐norm of solutions with respect to the physical viscosity coefficient may not be directly controllable. Furthermore, convex entropy‐entropy flux pairs may not produce signed entropy dissipation measures.

To overcome these difficulties, we first develop uniform energy‐type estimates with respect to the viscosity coefficient for solutions of the Navier‐Stokes equations and establish the existence of measure‐valued solutions of the isentropic Euler equations generated by the Navier‐Stokes equations. Based on the uniform energy‐type estimates and the features of the isentropic Euler equations, we establish that the entropy dissipation measures of the solutions of the Navier‐Stokes equations for weak entropy‐entropy flux pairs, generated by compactly supported C2 test functions, are confined in a compact set in H−1, which leads to the existence of measure‐valued solutions that are confined by the Tartar‐Murat commutator relation.

A careful characterization of the unbounded support of the measure‐valued solution confined by the commutator relation yields the reduction of the measurevalued solution to a Dirac mass, which leads to the convergence of solutions of the Navier‐Stokes equations to a finite‐energy entropy solution of the isentropic Euler equations with finite‐energy initial data, relative to the different end‐states at infinity. © 2010 Wiley Periodicals, Inc.
Donor/Acceptor Adsorbates on the Surface of Metal Oxide Nanoporous Films: A Spectroscopic Probe for Different Electron Transfer Pathways
Authors: Matylitsky Victor V. , Dworak Lars , Wachtveitl Josef
Published: May 2010

A composite model system which consists of a molecular donor/acceptor pair coupled to the surface of metal oxide nanoporous films is proposed to study the contribution of the surface trap states and their influence on the interfacial ET as well as charge trapping and spatial diffusion processes in films. The photophysics of this donor/acceptor system is investigated by time‐resolved transient absorbance spectroscopy in the UV/Vis (347–675 nm) spectral region. Variation of the band gap allows one to disentangle the ET pathways. Adsorption of the donor/acceptor pair on the nonreactive Al2O3 surface shows that coupling to the surface assists electron transfer between adsorbed donor and acceptor molecules, resulting in ultrafast intermolecular electron transfer of ∼100 fs. On the other hand, a competition between interfacial and intermolecular electron transfer is observed for the donor/acceptor pair coupled to a reactive TiO2 surface. The subsequent transfer of the conduction band electron to the electron acceptor is examined by monitoring the free charge carrier absorption in the mid‐IR (∼5 μm) spectral region.
Dynamic expression patterns of Nkx6.1 and Nkx6.2 in the developing mes‐diencephalic basal plate
Authors: Moreno‐Bravo Juan Antonio , Perez‐Balaguer Ariadna , Martinez Salvador , Puelles Eduardo
Published: May 2010

The components of the molecular codes needed to specify the different neuronal populations present in the basal neural tube are being identified. These codes become more intricate as we move to more anterior regions of the central nervous system. The aim of this study is to thoroughly analyze the expression pattern of Nkx6.1, Nkx6.2, and Pou4f1. These three genes are candidates to play an important role in the determination and differentiation of the basal nuclei of the mesencephalon and diencephalon. The results obtained have shown that there is a longitudinal domain positive for both Nkx6.1 and Nkx6.2 that is medial to the Pou4f1‐positive red nucleus. This domain could correspond to part of the reticular formation, which extends from the diencephalon and the mesencephalon. The nuclei integrated in this domain would be the rostral interstitial nucleus, the interstitial nucleus of Cajal, and a mesencephalic equivalent to these nuclei. Developmental Dynamics 239:2094–2101, 2010. © 2010 Wiley‐Liss, Inc.
Highly Crystalline, Idiomorphic Na2Ti6O13 Whiskers Grown from a NaCl Flux at a Relatively Low Temperature
Authors: Teshima Katsuya , Lee SunHyung , Murakoshi Serika , Suzuki Sayaka , Yubuta Kunio , Shishido Toetsu , Endo Morinobu , Oishi Shuji
Published: May 2010

Well‐developed, highly crystalline Na2Ti6O13 whiskers were successfully grown by cooling a NaCl flux at a relatively low temperature of 700 °C. The obtained Na2Ti6O13 whiskers were colorless and transparent. The whiskers grown at 700 °C were single phase and exhibit the lowest sizes of up to about 3.5 μm × 0.1 μm. From the results of SEM, XRD, and TEM, it was confirmed that the Na2Ti6O13 whiskers have very good crystallinity and elongated in the [lang]010[rang] directions. Furthermore, the whiskers exhibited good photocatalytic activity under ultraviolet light irradiation. It is reasonable to suppose that NaCl can be adequately used to synthesize high quality and well‐developed titanate whiskers in an environmentally friendly process of crystal growth.
Bora‐Amidinate Complexes of Lanthanide(II) Metals
Authors: Harder Sjoerd , Naglav Dominik
Published: May 2010

Reaction of (2‐Me2N‐α‐Me3Si‐benzyl)2Ln·(thf)2 (Ln = Yb, Eu and Sm) with one equivalent of DIPP(H)N‐BH‐N(H)DIPP (DIPPNBN‐H2, DIPP = 2,6‐iPr‐phenyl) gave the first LnII bora‐amidinate complexes which crystallized in the presence of THF as DIPPNBN‐Ln·(thf)4. Although only the Sm and Eu complex crystallize isomorphic, all three show similar structures. The very small N–Ln–N′ bite angles of 59.74(6)–63.28(9)° leave a large part of the metal coordination sphere available for neutral thf ligands.
New Approaches to 12‐Coordination: Structural Consequences of Steric Stress, Lanthanoid Contraction and Hydrogen Bonding
Authors: Chesman Anthony S. R. , Turner David R. , Deacon Glen B. , Batten Stuart R.
Published: May 2010

The anionic dinitrile ligand dicyanonitrosomethanide (dcnm), C(CN)2(NO)–, and the anion resulting from its addition product with water, carbamoylcyanonitrosomethanide (ccnm), C(CN)(CONH2)(NO)–, have been incorporated into lanthanoid complexes and display unusual η2(N,O) nitroso coordination modes. (Et4N)3[Ln(ccnm)6] (1Ln;1Ln=1La,1Ce,1Pr,1Nd,1Sm) and (Me4N)3[Ln(ccnm)6] (2Ln;2Ln=2La,2Ce,2Pr,2Nd) are systems containing 12‐coordinate homoleptic trianionic lanthanoidate complexes. The nitroso groups of the ccnm ligands form three‐membered ring chelates with the lanthanoid metal centre, with the asymmetry of the nitroso η2interactions dependent upon the intramolecular N–H···O=N hydrogen bonding. Additional intermolecular hydrogen bonding interactions exist between adjacent amide and nitrile groups giving rise to 3D α‐Po and 6,8‐connected (412.63)(420.68) networks in1Lnand2Ln, respectively. The compounds (Me4N)3[Ln(dcnm)6] (3Ln;3Ln=3La,3Ce,3Nd,3Sm) also contain a 12‐coordinate trianionic lanthanoidate complex with the nitroso group exhibiting a highly symmetrical η2interaction. The sterically crowded environments of [Ln(18‐crown‐6)(dcnm)3] (4Ln;4Ln = 4La,4Ce,4Pr,4Nd) result in a shift towards a more asymmetric η2bonding of the nitroso group with decrease in the Ln3+radius. There is a corresponding increase of the Ln–O–N angle, and one ligand is η1(O) binding in4Nd. The dcnm ligands in the discrete complexes [La(phen)3(dcnm)(3–x)Clx],x≈ 0.25 (5) (phen = 1,10‐phenanthroline), (Et4N)[Ce(phen)2(dcnm)4] (6a/b,6c) and [Ce(phen)2(dcnm)Cl2H2O] (7) display a variety of coordination modes. Complex5has 1D chains formed by π–π stacking of adjacent phen co‐ligands. Complexes6contain the monoanionic complex [Ce(phen)2(dcnm)4]–with two geometric isomers present in the crystal structure of6a/b. Complex7forms extended 1D chains via hydrogen bonding between coordinated water and chloride atoms and an extensive array of face‐to‐face π interactions.
Alkoxy‐5‐nitrosopyrimidines: Useful Building Block for the Generation of Biologically Active Compounds
Authors: Marchal Antonio , Nogueras Manuel , Sánchez Adolfo , Low John N. , Naesens Lieve , De Clercq Erik , Melguizo Manuel
Published: May 2010

Several alkoxy‐5‐nitrosopyrimidines were synthesised and high regioselective and sequential nucleophilic aromatic substitution of methoxy groups in 2‐amino‐4,6‐dimethoxy‐5‐nitrosopyrimidine was observed. The approach was applied to the synthesis of valuable polyfunctionalised aminopyrimidines capable of mimicking fused heterobicyclic derivatives of biological interest. In addition, new compounds were evaluated as antivirals and their usefulness as synthetic intermediates was demonstrated.
Self‐Acylation of 1‐Adamantylacetic Acid in Trifluoroacetic Anhydride Medium: A Route to 2,4‐Bis(1‐adamantyl)acetoacetic Acid and Its Derivatives
Authors: Kovalev Vladimir , Shokova Elvira , Shmailov Alexander , Vatsouro Ivan , Tafeenko Viktor
Published: May 2010

The self‐acylation of 1‐adamantylacetic acid (1) in trifluoroacetic anhydride, catalyzed by triflic acid, proceeds through the formation of the mixed 2,4‐bis(1‐adamantyl)acetoacetic–trifluoroacetic anhydride 2, and it was used as an efficient approach to previously unknown 2,4‐bis(1‐adamantyl)acetoacetic acid (3), its esters 4–6 and amides 7–11, and the sterically hindered 1‐adamantyl(1‐adamantylacetyl)ketene (12). The latter is stable in solution and can be isolated as a neat solid. Addition of methanol or primary amines to 12 gave the corresponding derivatives of acid 3. Acid 3 was decarboxylated to 1,3‐bis(1‐adamantyl)acetone (22), whereas theheterocyclization of phenyl ester 6 with thiourea gave two isomeric adamantylated thiouracils 23 and 24. The structures of N‐benzylamide 7 and thiouracil 23 were confirmed by single‐crystal X‐ray analysis. The utilization of the self‐acylation method for the conversion of some other aliphatic acids is discussed and preliminarily tested.
Novel Approach for the Synthesis of Five‐Membered‐Ring‐Fused Pyrazinones
Authors: Gembus Vincent , Janvier Solenn , Lecouvé Jean‐Pierre , Gloanec Philippe , Marsais Francis , Levacher Vincent
Published: May 2010

We describe a new route to access important pharmaceutical intermediates for the synthesis of constrained fused pyrazinones. These compounds are prepared in five to seven steps with a good overall yield from glycine methyl ester and commercial propanediol derivatives involving an intramolecular alkylation of a glycine moiety as key step.
Ecology, chorology and commonness of the Trifolium taxa in Greece
Authors: Fotiadis G. , Vrahnakis M. S. , Merou Th. , Vidakis K.
Published: May 2010

The taxa of the genus Trifolium L. are considered valuable genetic plant resources worldwide. The study of their chorological and floristic characteristics is of great importance. This paper aims at evaluating the taxa of the genus found in the flora of Greece in terms of their ecological, chorological and commonness characteristics. A floristic catalogue was produced based on published, but not genus‐specific, floristic data collected at various parts of the country and field surveys carried out by the authors in years 2004 and 2005. Information on the localities of the taxa, either found in the field surveys or scattered into floristic reports, was gathered. The present analysis was based on several research results and bibliographic information. It was found that the Greek flora contains 113 taxa (95 species, 17 subspecies, one hybrid) out of a total of approximately 255 species reported worldwide; six of them being Greek endemics. The taxa are distributed into two subgenera of the genus; subgenus Chronosemium including 14 species and subgenus Trifolium that includes 98 taxa (without counting one hybrid) distributed in five out of eight sections: Trifolium (56), Vesicaria (18), Trifoliastrum (15), Trichocephalum (7) and Paramesus (2). The majority of the taxa are mediterranean elements (38%), annuals (76%), therophytes (76%), and of scapose growth type (78%). It was also found that the centre of distribution of Trifolium is located in Anatolia (Turkey) and Greece, so pointing out this part of east Mediterranean as an important “gene‐pool” region. The most common Trifolium species in Greece are T. repens, T. campestre, T. fragiferum, T. physodes and T. arvense (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Seed morphology of some species of TephrosiaPers. (Fabaceae) from Saudi Arabia Identification of species and systematic significance
Authors: Al‐Ghamdi F. A. , Al‐Zahrani R. M.
Published: May 2010

Seed morphology of eight species belonging to the genus Tephrosia Pers. were examined by using light and scanning electron microscopy. Macro‐ and micromorphological characters, including seed shape, colour, size, surface, epidermal cell shape, anticlinal boundaries, outer periclinal cell wall and relief of outer cell walls, are presented. Two types of basic anticlinal cell wall boundaries and two types of relief outer cell walls are recognized and two different shapes of the outer periclinal cell wall are described. A key for the identification of the investigated taxa based on seed characters is provided (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Cadherin 13 in cancer
Authors: Andreeva Alexandra V. , Kutuzov Mikhail A.
Published: May 2010

We review the evidence suggesting the involvement of Cadherin 13 (CDH13, T‐cadherin, H‐cadherin) in various cancers. CDH13 is an atypical member of the cadherin family, devoid of a transmembrane domain and anchored to the exterior surface of the plasma membrane via a glycosylphosphatidylinositol anchor. CDH13 is thought to affect cellular behavior largely through its signaling properties. It is often down‐regulated in cancerous cells. CDH13 down‐regulation has been associated with poorer prognosis in various carcinomas, such as lung, ovarian, cervical and prostate cancer. CDH13 re‐expression in most cancer cell lines inhibits cell proliferation and invasiveness, increases susceptibility to apoptosis, and reduces tumor growth in in vivo models. These properties suggest that CDH13 may represent a possible target for therapy in some cancers. At the same time, CDH13 is up‐regulated in blood vessels growing through tumors and promotes tumor neovascularization. In contrast to most cancer cell lines, CDH13 overexpression in endothelial cells promotes their proliferation and migration, and has a pro‐survival effect. We also discuss molecular mechanisms that may regulate CDH13 expression and underlie its roles in cancer. © 2010 Wiley‐Liss, Inc.
Risk factors for developing synchronous esophageal neoplasia in patients with head and neck cancer
Authors: Wang Wen‐Lun , Lee Ching‐Tai , Lee Yi‐Chia , Hwang Tzer‐Zen , Wang Chih‐Chun , Hwang Jau‐Chung , Tai Chi‐Ming , Chang Chi‐Yang , Tsai Shang‐Shyue , Wang Cheng‐Ping , Ko Jenq‐Yuh , Lin Jaw‐Town
Published: May 2010

Background

This study investigated the risk factors for synchronous esophageal neoplasia in patients with head and neck squamous cell carcinoma (HNSCC).

Methods

All 315 consecutive patients with newly diagnosed HNSCC received endoscopic esophageal screening with image‐enhanced endoscopy.

Results

Sixty‐nine patients (21.9%) had synchronous esophageal neoplasia, 37 (53.6%) with superficial neoplasia and 21 (30.4%) with multiple esophageal lesions. Univariate analysis revealed age <50 years, drinking alcohol, and location of index HNSCC were significant risk factors for developing synchronous esophageal neoplasia. In multivariate analysis, drinking alcohol (odds ratio [OR], 3.792; p = .0035), index oropharynxgeal cancers (OR, 3.618; p = .0045) and hypopharyngeal cancers (OR, 2.627; p = .0029) were independent risk factors. Drinking alcohol was clearly dose–response related (p = .001).

Conclusion

Alcohol consumption and index tumor location are associated with the development of synchronous esophageal neoplasia in patients with HNSCC. Because of the high prevalence, routine endoscopic examination of the esophagus should be recommended, especially in patients with the risk factors identified. © 2010 Wiley Periodicals, Inc. Head Neck, 2011
Impact and management of airway obstruction in patients with squamous cell carcinoma of the larynx
Authors: Chu Pen‐Yuan , Lee Tsung‐Lun , Chang Shyue‐Yih
Published: May 2010

Background

We compared postoperative complications and oncologic results after laryngectomy of patients with laryngeal squamous cell carcinoma (SCC), with and without airway obstruction.

Methods

We retrospectively reviewed the medical records of 544 patients with laryngeal SCC between 1990 and 2000. Of 175 advanced cases receiving total laryngectomy, 32 initially presented with upper airway obstruction.

Results

Postoperative complications after laryngectomy did not differ significantly between patients with and without airway obstruction (36% vs 28%; p = .353). Although patients with airway obstruction had more T4 (81% vs 42%; p < .001) and stage IV disease (82% vs 48%; p = .0004), tumor recurrence rates did not increase (21% vs 29%; p = .374). Five‐year overall (52% vs 60%; p = .251), disease‐specific (73% vs 70%; p = .982), and relapse‐free (72% vs 68%; p = .982) survival did not differ significantly between groups.

Conclusion

After appropriate management of airway obstruction, the postoperative complications and oncologic results were similar to those without airway obstruction. © 2010 Wiley Periodicals, Inc. Head Neck, 2011
Evolving treatment strategies in thin cutaneous head and neck melanoma: 1 institution's experience
Authors: Jaber James J. , Clark Joseph I. , Muzaffar Kamil , Ruggiero Francis P. , Feustel Paul J. , Frett Michael J. , Zender Chad A.
Published: May 2010

Background

Although existing melanoma literature provides recommendations for thinner lesions (≤1 mm) within a heterogeneous population, a focus on the head and neck group is less pervasive.

Methods

The records of 49 node‐negative individuals with thin head and neck melanoma that underwent surgical intervention ± sentinel lymph node (SLN) biopsy were reviewed.

Results

A significant increased Breslow thickness and mitotic rate, and a trend toward significance in Clark level ≥ IV were shown in patients that underwent an SLN biopsy versus those that did not. The total number of positive biopsies was 2 (5%). In our subset analysis using the modified American Joint Committee on Cancer recommendations by Wong and colleagues, the incidence of positive SLN biopsy would have increased to 11%.

Conclusion

We advocate performing an SLN biopsy in thin head and neck melanomas for primary tumors > 0.75 mm, regardless of “high‐risk” features as described by Wong and colleagues. © 2010 Wiley Periodicals, Inc. Head Neck, 2011
Calpain 10 gene and laryngeal cancer: A survival analysis
Authors: Moreno‐Luna Ramón , Abrante Antonio , Esteban Francisco , González‐Moles Miguel Angel , Delgado‐Rodríguez Miguel , Sáez María Eugenia , González‐Pérez Antonio , Ramírez‐Lorca Reposo , Real Luis Miguel , Ruiz Agustín
Published: May 2010

Background

Laryngeal carcinoma is a common upper respiratory tract cancer with different environmental and genetic factors involved in its development. Calpains are Ca2+‐dependent cysteine proteases that modulate cellular function. A novel association between calpain 10 (CAPN10) haplotypes and laryngeal cancer has been found recently. Therefore, the goal of this study was to analyze the contribution of CAPN10 alleles to laryngeal cancer survival.

Methods

Patients were recruited from southern Spain. Genotypes were determined using pyrosequencing technology. We analyzed CAPN10 UCSNP‐44, UCSNP‐43, UCSNP‐19, and UCSNP‐63 allelic distributions in 199 patients with unrelated laryngeal cancer. Survival curves were calculated from the date of the intervention to the date of death. Multivariate analyses were done using the Cox proportional risk model.

Results

UCSNP‐19, UCSNP‐43, and UCSNP‐44 were unrelated to survival in both univariate and multivariate analyses. However, for UCSNP‐63 genotype 12 a significant relationship was observed in multivariate analysis (hazard ratio [HR] = 2.73; 95% confidence interval [CI], 1.21–6.20).

Conclusion

CAPN10 UCSNP‐63 genotype 12 seems to be related with a worse prognosis in laryngeal cancer. © 2010 Wiley Periodicals, Inc. Head Neck, 2011
Associations between quality of life, coping styles, optimism, and anxiety and depression in pretreatment patients with head and neck cancer
Authors: Horney Debbie J. , Smith Helen E. , McGurk Mark , Weinman John , Herold Jim , Altman Keith , Llewellyn Carrie D.
Published: May 2010

Background

Head and neck cancer is often diagnosed at a late stage and consequently radical treatment is necessary. The pretreatment phase is a time of high anxiety and depression for patients. This study aimed to investigate whether anxiety and depression are related to quality of life, coping styles, and dispositional optimism.

Methods

One hundred and three patients were recruited after diagnosis to a questionnaire study. Measures included the Hospital Anxiety and Depression Scale; SF12v2 Health Survey; Brief COPE, and the Revised Life Orientation Test.

Results

Quality of life, in particular emotional role explained a large proportion of the variance in pretreatment anxiety and depression. In addition, the use of negative coping styles was related to high anxiety levels and low levels of optimism were related to higher levels of depression.

Conclusion

There are a small but significant proportion of pretreatment patients that may benefit from individualized support. © 2010 Wiley Periodicals, Inc. Head Neck, 2011
Preoperative CT diagnosis of right nonrecurrent inferior laryngeal nerve
Authors: Wang Yu , Ji Qinghai , Li Duanshu , Wu Yi , Zhu Yongxue , Huang Caiping , Shen Qiang , Wang Zhuoying , Zhang Ling , Sun Tuanqi
Published: May 2010

Background

The nonrecurrent inferior laryngeal nerve is an anomaly associated with the absence of the brachiocephalic artery (BCA) and the presence of arteria lusoria.

Methods

The preoperative CT scans from 290 patients (9 nonrecurrent, 281 recurrent) were retrospectively reviewed. We identified the BCA or the arteria lusoria, and classified the relationship between the right subclavian artery (SCA) and the tracheoesophagus into 2 subtypes.

Results

The arteria lusoria was identified in 6 nonrecurrent cases. The BCA was identified in 143 recurrent cases. The right SCA was detected on the ventral side of the membranous wall of the trachea in 273 recurrent cases, whereas it was detected on the dorsal side in 8 recurrent cases with enlarged thyroid, and it was detected on the dorsal side in 9 nonrecurrent cases without pressure sign.

Conclusions

It is possible to predict a nonrecurrent inferior laryngeal nerve by identifying the arteria lusoria or other features on the preoperative CT. © 2010 Wiley Periodicals, Inc. Head Neck, 2011
Signet ring carcinoma parotid gland: A case report
Authors: Singh Meeta , Khurana Nita , Wadhwa Rachna , Gulati Achal
Published: May 2010

Background

Signet ring adenocarcinoma is a recently characterized entity occurring in the minor salivary glands. All reported cases have occurred in minor salivary gland. Pure signet ring adenocarcinoma of a major salivary gland has not been reported in the literature.

Methods

A 38‐year‐old woman presented with a mass in the parotid region. Microscopy showed signet ring cells positive for mucicarmine. Immunohistochemistry showed cytokeratin and focal smooth muscle actin (SMA) positivity; an exhaustive search for primary elsewhere did not reveal any suspicious focus.

Results

A diagnosis of low‐grade signet ring adenocarcinoma of the parotid gland was made. On 6‐month follow‐up the patient was alive and well.

Conclusions

The present case highlights a rare occurrence of this tumor in the parotid gland, which until now was labeled as a tumor exclusive to minor salivary glands. Thus this entity should be kept as a differential while investigating mucinous tumors of parotid. © 2010 Wiley Periodicals, Inc. Head Neck, 2011
Small Molecular Compounds that Inhibit Hepatitis C Virus Replication Through Destabilizing Heat Shock Cognate 70 Messenger RNA†
Authors: Peng Zong-Gen , Fan Bo , Du Na-Na , Wang Yu-Ping , Gao Li-Mei , Li Ying-Hong , Li Yu-Huan , Liu Fei , You Xue-Fu , Han Yan-Xing , Zhao Zhi-Yun , Cen Shan , Li Jian-Rui , Song Dan-Qing , Jiang Jian-Dong
Published: May 2010

Host heat shock cognate 70 (Hsc70) protein is packaged into hepatitis C viral (HCV) particles as a structural component of the virus in the assembly process. It helps HCV RNA release into the cytoplasm in the next infection cycle. The goal of this study is to investigate whether chemically down-regulating host Hsc70 expression could be a novel strategy to interrupt HCV replication. Compounds were screened with an Hsc70 messenger RNA (mRNA) assay. IMB-DM122 was found to be an effective and safe inhibitor for Hsc70 mRNA/protein expression in human hepatocytes. IMB-DM122 inhibited HCV replication through destabilization of Hsc70 mRNA, and the half-life of host Hsc70 mRNA was reduced by 78% after the compound treatment. The Hsc70 mRNA 3′ untranslated region sequence is the element responsible for the effect of IMB-DM122 on Hsc70 mRNA. The compound appears to be highly efficient in inhibiting Hsc70-related HCV replication. Treatment of the HCV-infected hepatocytes with IMB-DM122 reduced the virion encapsidation of Hsc70, and therefore disrupted HCV replication and the infection cycle. IMB-DM122 showed considerable good safety

in vitro

as well as

in vivo

with no indication of harmful effect on liver and kidney functions.

Conclusion:

Hsc70 might be a new drug target and mechanism to inhibit HCV proliferation.
Delineating low‐count defective‐contour SPECT lung scans for PE diagnosis using adaptive dual exponential thresholding and active contours
Authors: Wang Alex , Yan Hong
Published: May 2010

To develop an automated lung delineation method that greatly improves the accuracy of contour extraction in SPECT lung scans with low maximum count, total counts, and/or defective contour edges, by combining deformable contour and planar image processing techniques with our existing adaptive dual exponential thresholding method. Two datasets consisting of 90 Monte Carlo simulations and 35 SPECT scans of real patients both with low maximum/total counts were used as the basis of this study. After preliminary contour extraction using dual exponential thresholding, a deformable contour algorithm was applied, combined with edge enhancement using image processing techniques such as Gaussian transformation and Sobel edge detection. Both quantitative validation via statistical measures and qualitative verification by an experienced practitioner were implemented to evaluate the method. An average of 83% congruency was achieved for 45 simulations with maximum count values below 31. This is a significant 33% improvement on the results of our previous study using dual exponential thresholding alone. Overall congruence averaged 95% for the entire simulation dataset. With the set of 35 actual SPECT scans with relatively low maximum/total counts, congruency again averaged near 95% with a few outliers ranging between 75 and 90%. We have successfully combined active contour with adaptive dual exponential thresholding to delineate lung contours accurately for SPECT scans with low maximum/total counts and/or defective contours due to various cardiopulmonary disorders. © 2010 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 20, 149–154, 2010
Computer‐based morphometry of brain
Authors: Koo Bang‐Bon , Kim Dae‐Shik
Published: May 2010

Over the past decade, the importance of probing the anatomy of the brain has reemerged as an important field of neuroscience. In combination with functional imaging techniques, the rapid advancement of neuroimaging techniques—such as magnetic resonance imaging—and their growing applicability in studying brain morphometry has led to great advances in neuroscience research. Considering the requirements of the diverse technologies—from image processing to statistics—in performing morphometry of the brain, it is critical to have an overall understanding of this subject. The major objective of this review is to provide a practical introduction to this field. The review starts by covering basic concepts and techniques that are commonly used in morphometry of structural magnetic resonance imaging and then extends to further technical perspectives. © 2010 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 20, 117–125, 2010
Protein adsorption on biodegradable polyanhydride microparticles
Authors: Carrillo‐Conde Brenda , Garza Alicia , Anderegg James , Narasimhan Balaji
Published: May 2010

The in vitro adsorption of plasma proteins on polyanhydride microparticles based on sebacic acid (SA), 1,6‐bis(p‐carboxyphenoxy)hexane (CPH), and 1,8‐bis(p‐carboxyphenoxy)‐3,6‐dioxaoctane (CPTEG) was studied. Three model proteins from bovine serum (albumin (BSA), immunoglobulin G (IgG), and fibrinogen (Fg)) were used. The adsorption was studied using X‐Ray Photoelectron Spectroscopy and gel electrophoresis. 2D electrophoresis was used to study the adsorption of plasma proteins from bovine serum. Differences in the amount of protein adsorbed were detected as a function of the following: (i) copolymer composition and (ii) specific protein studied. A direct correlation between polymer hydrophobicity and protein adsorbed was observed and higher quantities of Fg and IgG were absorbed. In vitro release studies were performed with ovalbumin‐encapsulated microparticles that were incubated with Fg; these studies showed a reduction in the amount of ovalbumin released from the microparticles when Fg is adsorbed on the surface. An understanding of protein adsorption patterns on parenteral delivery devices is valuable in optimizing their in vivo performance. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010
Nicotinamide phosphoribosyltransferase/sirtuin 1 pathway is involved in human immunodeficiency virus type 1 Tat‐mediated long terminal repeat transactivation
Authors: Zhang Hong‐Sheng , Sang Wei‐Wei , Wang Yu‐Ou , Liu Wei
Published: May 2010

Tat is a multifunctional transactivator encoded by human immunodeficiency virus type 1 (HIV‐1). Tat transactivating activity is controlled by nicotinamide adenine nucleotide+ (NAD+)‐dependent deacetylase sirtuin 1 (SIRT1). Nicotinamide phosphoribosyltransferase (Nampt) is a rate‐limiting enzyme in the conversion of nicotinamide into NAD+, which is crucial for SIRT1 activation. Thus, the effect of Nampt on Tat‐regulated SIRT activity was studied in Hela‐CD4‐β‐gal (MAGI) cells. We demonstrated that Tat caused NAD+ depletion and inhibited Nampt mRNA and protein expression in MAGI cells. Resveratrol reversed Tat‐induced NAD+ depletion and inhibition of Nampt mRNA and protein expression. Further investigation revealed that Tat‐induced inhibition of SIRT1 activity was potentiated in Nampt‐knockdown by Nampt siRNA compared to treatment with Tat alone. Nampt siRNA potentiated Tat‐induced HIV‐1 transactivation in MAGI cells. Altogether, these results indicate that Nampt is critical in the regulation of Tat‐induced inhibition of SIRT1 activity and long terminal repeat (LTR) transactivation. Nampt/SIRT1 pathway could be a novel therapeutic tool for the treatment of HIV‐1 infection. J. Cell. Biochem. 110: 1464–1470, 2010. © 2010 Wiley‐Liss, Inc.
Extracellular high K+ stimulates vesicular glutamate release from astrocytes by activating voltage‐dependent calcium channels
Authors: Yaguchi Takahiro , Nishizaki Tomoyuki
Published: May 2010

Extracellular high K+ (75 mM) increased intracellular Ca2+ concentrations in cultured rat hippocampal astrocytes, and the Ca2+ rise was abolished by deleting extracellular Ca2+ or cadmium, a non‐selective inhibitor of voltage‐dependent calcium channels (VDCCs). In the reverse transcription‐polymerase chain reaction analysis, cultured astrocytes expressed mRNAs for L type‐VDCC subunits such as α1B, α1C, α1D, and α1E. Extracellular high K+ (75 mM) stimulated glutamate release from astrocytes. The glutamate release was not prevented by the glutamate transporter inhibitor, L‐trans‐pyrrolidine‐2,4‐dicarboxylic acid (PDC), or deleting extracellular Na+, but otherwise it was clearly inhibited by deleting extracellular Ca2+, cadmium, vesicular transport inhibitors such as brefeldin A, bafilomycin A1, and latrunculin B, or botulinum toxin‐A, an exocytosis inhibitor. Extracellular high K+ (75 mM) bleached fluorescent signals of FM1‐43, taken up into the vesicular membrane in astrocytes, that was also inhibited by deleting extracellular Ca2+, cadmium, brefeldin A, bafilomycin A1, latrunculin B, or botulinum toxin‐A, but not by PDC. Taken together, the results of the present study indicate that extracellular high K+‐evoked depolarization activates VDCCs expressed in astrocytes, causing an increase in intracellular Ca2+ concentrations through VDCCs, which triggers vesicular glutamate release from astrocytes, independently of reverse transport through glutamate transporters. J. Cell. Physiol. 225: 512–518, 2010. © 2010 Wiley‐Liss, Inc.
Hierarchical clustering of flow cytometry data for the study of conventional central chondrosarcoma
Authors: Diaz‐Romero Jose , Romeo Salvatore , Bovée Judith V.M.G. , Hogendoorn Pancras C.W. , Heini Paul F. , Mainil‐Varlet Pierre
Published: May 2010

We have investigated the use of hierarchical clustering of flow cytometry data to classify samples of conventional central chondrosarcoma, a malignant cartilage forming tumor of uncertain cellular origin, according to similarities with surface marker profiles of several known cell types. Human primary chondrosarcoma cells, articular chondrocytes, mesenchymal stem cells, fibroblasts, and a panel of tumor cell lines from chondrocytic or epithelial origin were clustered based on the expression profile of eleven surface markers. For clustering, eight hierarchical clustering algorithms, three distance metrics, as well as several approaches for data preprocessing, including multivariate outlier detection, logarithmic transformation, and z‐score normalization, were systematically evaluated. By selecting clustering approaches shown to give reproducible results for cluster recovery of known cell types, primary conventional central chondrosacoma cells could be grouped in two main clusters with distinctive marker expression signatures: one group clustering together with mesenchymal stem cells (CD49b‐high/CD10‐low/CD221‐high) and a second group clustering close to fibroblasts (CD49b‐low/CD10‐high/CD221‐low). Hierarchical clustering also revealed substantial differences between primary conventional central chondrosarcoma cells and established chondrosarcoma cell lines, with the latter not only segregating apart from primary tumor cells and normal tissue cells, but clustering together with cell lines from epithelial lineage. Our study provides a foundation for the use of hierarchical clustering applied to flow cytometry data as a powerful tool to classify samples according to marker expression patterns, which could lead to uncover new cancer subtypes. J. Cell. Physiol. 225: 601–611, 2010. © 2010 Wiley‐Liss, Inc.