bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of Indolobenzazepinones by Application of an Isocyanide‐Based Multicomponent Reaction
Authors: Beaumont Stéphane , Retailleau Pascal , Dauban Philippe , Dodd Robert H.
Published: September 2008

Application of a Ugi multicomponent reaction to oxo acids 4 allows the formation of potentially antimitotic indolobenzazepinones of type 5 in good yields of up to 72 %, whereas the same transformation from the starting substrate 6 gives access to analogues of paullone with yields of up to 89 %. The reaction could be applied to a wide range of isocyanides, thereby ensuring introduction of molecular diversity at the key C‐5 position. Use of cyclohexenyl isocyanide allows post‐condensation modifications, while careful choice of the amine and the indole protecting groups proved to be important for providing the deprotected compounds necessary for biological tests. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Synthesis of L‐ and D‐4,6‐Dideoxyhexoses and 4,6‐Dideoxy‐C‐phenylglycosides from Enzyme‐Generated Products
Authors: Acetti Daniela , Brenna Elisabetta , Fuganti Claudio , Gatti Francesco G. , Malpezzi Luciana , Serra Stefano
Published: September 2008

Optically active 1,3‐diols 1 were prepared by biocatalysed routes. The synthetic versatility of compounds 1 as chiral building blocks was shown. The oxidative cleavage of the double bond afforded a carbonyl moiety, which allowed for elongation by Grignard addition and further derivatisation to make deoxy sugars readily available. The epoxidation of the same double bond allowed the direct intramolecular opening of the epoxide ring to generate deoxy C‐phenylglycosides. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Hydrolytic Deallylation of N‐Allyl Amides Catalyzed by PdII Complexes
Authors: Ohmura Naoya , Nakamura Asami , Hamasaki Akiyuki , Tokunaga Makoto
Published: September 2008

Hydrolytic deallylation of N‐allyl amides to give amides and propanal can be achieved with PdII catalysts. The optimized catalyst consists of Pd(OCOCF3)2 and 1,3‐bis(diphenylphosphanyl)propane (DPPP). Several kinds of open‐chain N‐allyl amides and N‐allyl lactams undergo hydrolytic deallylation to give the corresponding amides and lactams in good to high yield. A mechanism which includes isomerization to enamides and subsequent hydrolysis is proposed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Electrochemical Study of Chitosan‐SiO2‐MWNT Composite Electrodes for the Fabrication of Cholesterol Biosensors
Authors: Tiwari Ashutosh , Gong Shaoqin
Published: September 2008

We report a novel composite electrode made of chitosan‐SiO2‐multiwall carbon nanotube (CHIT‐SiO2‐MWNT) composite coated on the indium‐tin oxide (ITO) glass substrate. Cholesterol oxidase (ChOx) was covalently immobilized on the CHIT‐SiO2‐MWNT/ITO electrode that resulted in a ChOx/CHIT‐SiO2‐MWNT/ITO cholesterolactive bioelectrode. The CHIT‐SiO2‐MWNT/ITO and ChOx/CHIT‐SiO2‐MWNT/ITO electrodes were characterized with Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The influence of various parameters was investigated, including the applied potential, pH of the medium, and the concentration of the enzyme on the performance of the biosensor. The cholesterol bioelectrode exhibited a sensitivity of 3.4 nA/ mgdL−1 with a response time of five seconds. The biosensor using ChOx/CHIT‐SiO2‐MWNT/ITO as the working electrode retained its original response after being stored for six months. The biosensor using ChOx/CHIT‐SiO2‐MWNT/ITO as the working electrode showed a linear current response to the cholesterol concentration in the range of 50–650 mg/dL.
Electrochemical and Electrocatalytic Properties of Imidazole Analogues of the Redox Cofactor Pyrroloquinoline Quinone
Authors: Lumibao Claudine Y. , Tillekeratne L. M. Viranga , Kirchhoff Jon R. , Fouchard David M. D. , Hudson Richard A.
Published: September 2008

The electrochemical and electrocatalytic properties of two synthetic imidazole analogues of the redox cofactor pyrroloquinoline quinone (PQQ) were evaluated. Cyclic voltammetry measurements as a function of pH indicated that both 4,5‐dihydro‐4,5‐dioxo‐1H‐imidazolo[5,4‐f]quinoline‐7,9‐dicarboxylic acid (1) and 4,5‐dihydro‐4,5‐dioxo‐2‐methyl‐1H‐imidazolo[5,4‐f]quinoline‐7,9‐dicarboxylic acid (2) undergo a reversible reduction of theo‐quinone moiety below pH 8 with potentials slightly more positive than those observed for PQQ. Upon incorporation into a polypyrrole membrane on the tip of a glassy carbon electrode,1and2exhibited electrocatalytic properties sufficient for the indirect amperometric detection of cysteine. The response for cysteine was linear up to 1 mM over a wide pH range. Detection limits (S/N=3) were in the μM range and dependent on the solution pH. Interference from redox active species such as dopamine and uric acid were minimized by the pH‐dependent redox potentials of1and2and thus the ability to tune the detection potential.
Amperometric Detection and Quantification of 8‐Hydroxy‐2′‐deoxyguanosine (8‐OHdG) Using Dendrimer Modified Electrodes
Authors: Gutiérrez Alejandro , Osegueda Soraya , Gutiérrez‐Granados Silvia , Alatorre Alejandro , García Ma. Guadalupe , Godínez Luis A.
Published: September 2008

8‐Hydroxy‐2′‐deoxyguanosine (8‐OHdG) detection by high performance liquid chromatography (HPLC) with amperometric detection was studied using a Au electrode modified with different dendrimer based thin films. Gold electrode is thiol‐modified, forming self‐assembled monolayers on which different generation PAMAM dendrimers with terminal functional groups COOH and NH2 have been attached using peptidic bonds. Results obtained in synthetic samples show low limits of detection and quantification for 8‐OHdG (1.2×10−9 and 3.7×10−9 M respectively), with matrix interference elimination, thus avoiding sample pretreatment. Best results are obtained with electrodes modified with aliphatic amino thiols and 3.5 and 4.5 generation carboxylated dendrimers (Au/AET/DG3.5 and Au/AET/DG4.5), demonstrating that these materials constitute a good alternative for 8‐OHdG determination in biological fluids.
Incorporating spatially variable bottom stress and Coriolis force into 2D, a posteriori, unstructured mesh generation for shallow water models
Authors: Parrish D. Michael , Hagen Scott C.
Published: September 2008

An enhanced version of our localized truncation error analysis with complex derivatives (LTEA−CD ) a posteriori approach to computing target element sizes for tidal, shallow water flow, LTEA+CD , is applied to the Western North Atlantic Tidal model domain. The LTEA + CD method utilizes localized truncation error estimates of the shallow water momentum equations and builds upon LTEA and LTEA−CD‐based techniques by including: (1) velocity fields from a nonlinear simulation with complete constituent forcing; (2) spatially variable bottom stress; and (3) Coriolis force. Use of complex derivatives in this case results in a simple truncation error expression, and the ability to compute localized truncation errors using difference equations that employ only seven to eight computational points. The compact difference molecules allow the computation of truncation error estimates and target element sizes throughout the domain, including along the boundary; this fact, along with inclusion of locally variable bottom stress and Coriolis force, constitute significant advancements beyond the capabilities of LTEA. The goal of LTEA + CD is to drive the truncation error to a more uniform, domain‐wide value by adjusting element sizes (we apply LTEA + CD by re‐meshing the entire domain, not by moving nodes). We find that LTEA + CD can produce a mesh that is comprised of fewer nodes and elements than an initial high‐resolution mesh while performing as well as the initial mesh when considering the resynthesized tidal signals (elevations). Copyright © 2008 John Wiley & Sons, Ltd.
Performance of a Glucose/O2 Enzymatic Biofuel Cell Containing a Mediated Melanocarpus albomyces Laccase Cathode in a Physiological Buffer
Authors: Kavanagh P. , Boland S. , Jenkins P. , Leech D.
Published: September 2008

We report on the performance of a prototype glucose/O2 biofuel cell in a physiological buffer. The cell consists of cathode based on Melanocarpus albomyces laccase (with a reported T1 copper redox potential of + 0.26 V vs. Ag/AgCl) co‐immobilised with an osmium redox polymer mediating film on glassy carbon (GC) separated by a Nafion 117 membrane from a GC anode in anolyte of glucose oxidase, N,N,N′,N′‐tetramethyl‐p‐phenylenediamine (TMPD) as a mediator, all immersed in pH 7.4 phosphate buffer solution containing 0.15 M NaCl and dissolved oxygen, thermostated at 37 °C, mimicking physiological conditions. Two osmium redox polymers are employed for cathodic mediation: [Os(2,2′‐bipyridine)2(polyvinylimidazole)10Cl]+/2+ (E°′ 0.22 V vs. Ag/AgCl) and [Os(4,4′‐dichloro‐2,2′‐bipyridine)2(polyvinylimidazole)10Cl]+/2+ (E°′ 0.35 V vs. Ag/AgCl). Power outputs of 52 μW cm–2 at 0.21 V and 17 μW cm–2 at 0.34 V were obtained for assembled fuel cells containing the respective redox polymer‐mediated laccase cathodes, illustrating the increased power obtained as a result of higher biocatalytic efficiency using a redox polymer with redox potential tailored for the enzyme.
Kinetics of Anode Reactions for a Yeast‐Catalysed Microbial Fuel Cell
Authors: Ganguli R. , Dunn B. S.
Published: September 2008

Chronoamperometric investigations with rotating disc electrodes (RDEs) were used to characterise the anodic half‐cell of yeast powered microbial fuel cells using methylene blue (MB) as a mediator. Both convection and mediator adsorption were shown to affect the anodic current. A microbe–mediator limited reaction model was developed and shown to agree well with the experimental data. A power density of ∼150 μW cm–2 was achieved in a full cell, which represented a significant increase from prior reports on yeast‐catalysed fuel cells. The increased power density was enabled by using high mediator concentrations and by controlling the mediator adsorption.
Palliative radiation therapy for head and neck cancer: Toward an optimal fractionation scheme
Authors: Chen Allen M. , Vaughan Andrew , Narayan Samir , Vijayakumar Srinivasan
Published: September 2008

Background.

To analyze the efficacy of various fractionation schedules for the palliation of head and neck cancer with radiation therapy.

Methods.

Sixty patients completed palliative irradiation to primary head and neck sites. The most commonly used fractionation regimen was the one previously described by the Radiation Therapy Oncology Group (RTOG) protocol 85‐02 and was designed to deliver 440 cGy using 370 cGy fractionation, administered twice a day for 2 consecutive days at 2‐ to 3‐week intervals for 3 total cycles.

Results.

The rates of palliative response were 83%, 77%, 67%, 86%, and 60% among those treated using the RTOG regimen, 7000 cGy/35 fractions, 3000 cGy/10 fractions, 3750 cGy/15 fractions, and 2000 cGy/5 fractions, respectively (p = .42). Nine percent (2/23) of those treated with the RTOG regimen developed grade 3+ toxicity compared with 37% among those treated with other schedules (p = .01).

Conclusion.

Although all of the analyzed schedules were effective at providing palliation, the RTOG 85‐02 regimen was associated with less toxicity. © 2008 Wiley Periodicals, Inc. Head Neck, 2008
Regulation of IAPs gene family by interleukin‐1α and Epstein‐Barr virus in nasopharyngeal carcinoma
Authors: Chua Huey‐Huey , Yeh Te‐Huei , Wang Ying‐Piao , Sheen Tzung‐Shiahn , Shew Jin‐Yuh , Huang Yu‐Tzu , Tsai Ching‐Hwa
Published: September 2008

Background.

Inhibitors of apoptosis proteins (IAPs), which counteract apoptosis by potently inhibiting caspase activation, are promising targets of new anti‐tumor therapy. However, their roles in the pathogenesis of nasopharyngeal carcinoma (NPC), an Epstein‐Barr virus (EBV)‐associated carcinoma, are not fully understood. Herein, we investigated the expression and regulation of IAPs in NPC.

Methods and Results.

Using real‐time quantitative polymerase chain reaction (PCR) analysis, we found that among the IAPs family only the transcription of survivin, HIAP‐1, and HIAP‐2 was consistently up‐regulated in NPC and metastatic NPC tissues. Immunohistochemical staining showed that their proteins were more predominantly expressed in tumor cells nests. Noteworthy, these IAPs were upregulated by interleukin‐1α stimulation or EBV infection, and subsequently resulted in triggering rapid proliferation of NPC verified by strong Ki‐67 staining.

Conclusion.

Survivin, HIAP‐1, and HIAP‐2 were distinctly upregulated in NPC, suggesting they may play significant roles in NPC tumorigenesis and serve as tumor markers with prognostic and therapeutic implications. © 2008 Wiley Periodicals, Inc. Head Neck, 2008
Biochemotherapy in patients with advanced head and neck mucosal melanoma
Authors: Bartell Holly L. , Bedikian Agop Y. , Papadopoulos Nicholas E. , Dett Tina K. , Ballo Matthew T. , Myers Jeffrey N. , Hwu Patrick , Kim Kevin B.
Published: September 2008

Background.

No systemic therapy regimen has been recognized as effective for metastatic mucosal melanoma of the head and neck. We retrospectively analyzed the effectiveness of biochemotherapy in patients with advanced head and neck mucosal melanoma.

Methods.

We evaluated the medical records of 15 patients at our institution who had received various biochemotherapy regimens for advanced head and neck mucosal melanoma.

Results.

After a median follow‐up duration of 13 months, 3 patients (20%) had partial response, and 4 patients (27%) had complete response. The median time to disease progression for all 15 patients was 10 months. The median overall survival duration for all patients was 22 months.

Conclusions.

Although this was a small study, our results, especially the high complete response and overall response rates, indicate that biochemotherapy for advanced head and neck mucosal melanoma should be considered as a systemic treatment option for patients with this aggressive malignancy. © 2008 Wiley Periodicals, Inc. Head Neck, 2008
Esthesioneuroblastoma: The Princess Margaret Hospital experience
Authors: Bachar Gideon , Goldstein David P. , Shah Manish , Tandon Asheesh , Ringash Jolie , Pond Gregory , Gullane Patrick J. , Perez‐Ordonez Bayardo , Gilbert Ralph W. , Brown Dale H. , Gentili Fred , O'Sullivan Brian , Irish Jonathan C.
Published: September 2008

Background.

Esthesioneuroblastoma is rare. The aim of the study was to review our experience and to evaluate the staging system and treatment that best correlates with the patient outcome.

Methods.

Thirty‐nine patients were identified between 1972 and 2006.

Results.

At presentation 10% had cervical metastases. None had distant metastasis. Five were treated with surgery, 2 with chemotherapy, 1 with radiotherapy, and 30 with surgery and radiation. Local disease control was 82.6% at 5 years. Recurrence was seen in 33% with local and regional disease recurrence at 15% and 18%, respectively. The 5‐ and 10‐year overall survival rates were 87.9% and 69.2%, respectively. Dulguerov classification correlated most closely to survival and recurrence.

Conclusions.

Dulguerov classification best correlates with the patient's outcome. A combined approach is the preferred treatment. It makes no difference whether radiotherapy is given pre or postsurgical resection. Recurrence can occur even 15 years after treatment. Therefore, long‐term follow‐up is essential. © 2008 Wiley Periodicals, Inc. Head Neck, 2008
Distant metastases after transoral laser microsurgery for laryngeal and hypopharyngeal squamous cell carcinoma
Authors: Caballero Miguel , Vilaseca Isabel , Bernal‐Sprekelsen Manuel , Guilemany Jose M. , Moragas Miguel , Blanch Jose Luís
Published: September 2008

Background.

Transoral CO2 laser microsurgery (TLM) resection of laryngeal–hypopharyngeal squamous cell carcinomas has become a standard procedure. The objective was to evaluate whether there is a relationship between TLM and a higher incidence of distant metastases.

Methods.

We conducted a retrospective analysis of 340 consecutive patients with laryngeal or hypopharyngeal squamous cell carcinoma treated with TLM.

Results.

Distant metastases occurred in 24 of 340 (7.1%) patients. The mean time of distant metastases diagnosis was 19.1 months (range, 1–41) postsurgery. Univariate study demonstrated an association with alcoholism (p = .008), tumor site (p<.001), grade of differentiation (p = .032), stage (p<.001), tumor classification (T; p = .001), node involvement (N; p<.001), extracapsular node spread (p<.001), and positive surgical margin (p = .004). In multivariate logistic regression analysis, location (sinus piriform: OR = 15.37, p = .025), node involvement (N2: OR = 7.36, p = .003; N3: OR = 19.28, p = .027), and the affected surgical margin (OR 5.32; p = .005) predicted an increased likelihood of distant metastases.

Conclusions.

Development of distant metastases after TLM in patients with squamous cell carcinoma depends mainly on the tumor site, the presence of metastatic lymph node disease, and the margin status after resection. © 2008 Wiley Periodicals, Inc. Head Neck, 2008
The impact of land use change and check‐dams on catchment sediment yield
Authors: Boix‐Fayos Carolina , de Vente Joris , Martínez‐Mena María , Barberá Gonzalo G. , Castillo Víctor
Published: September 2008

Extensive land use changes have occurred in many areas of SE Spain as a result of reforestation and the abandonment of agricultural activities. Parallel to this the Spanish Administration spends large funds on hydrological control works to reduce erosion and sediment transport. However, it remains untested how these large land use changes affect the erosion processes at the catchment scale and if the hydrological control works efficiently reduce sediment export. A combination of field work, mapping and modelling was used to test the influence of land use scenarios with and without sediment control structures (check‐dams) on sediment yield at the catchment scale. The study catchment is located in SE Spain and suffered important land use changes, increasing the forest cover 3‐fold and decreasing the agricultural land 2·5‐fold from 1956 to 1997. In addition 58 check‐dams were constructed in the catchment in the 1970s accompanying reforestation works.

The erosion model WATEM‐SEDEM was applied using six land use scenarios: land use in 1956, 1981 and 1997, each with and without check‐dams. Calibration of the model provided a model efficiency of 0·84 for absolute sediment yield. Model application showed that in a scenario without check dams, the land use changes between 1956 and 1997 caused a progressive decrease in sediment yield of 54%. In a scenario without land use changes but with check‐dams, about 77% of the sediment yield was retained behind the dams. Check‐dams can be efficient sediment control measures, but with a short‐lived effect. They have important side‐effects, such as inducing channel erosion downstream. While also having side‐effects, land use changes can have important long‐term effects on sediment yield. The application of either land use changes (i.e. reforestation) or check‐dams to control sediment yield depends on the objective of the management and the specific environmental conditions of each area. Copyright © 2008 John Wiley & Sons, Ltd.
Effects of 2003 wildfires on stream chemistry in Glacier National Park, Montana
Authors: Mast M. Alisa , Clow David W.
Published: September 2008

Changes in stream chemistry were studied for 4 years following large wildfires that burned in Glacier National Park during the summer of 2003. Burned and unburned drainages were monitored from December 2003 through August 2007 for streamflow, major constituents, nutrients, and suspended sediment following the fires. Stream‐water nitrate concentrations showed the greatest response to fire, increasing up to tenfold above those in the unburned drainage just prior to the first post‐fire snowmelt season. Concentrations in winter base flow remained elevated during the entire study period, whereas concentrations during the growing season returned to background levels after two snowmelt seasons. Annual export of total nitrogen from the burned drainage ranged from 1·53 to 3·23 kg ha−1 yr−1 compared with 1·01 to 1·39 kg ha−1 yr−1 from the unburned drainage and exceeded atmospheric inputs for the first two post‐fire water years. Fire appeared to have minimal long‐term effects on other nutrients, dissolved organic carbon, and major constituents with the exception of sulfate and chloride, which showed increased concentrations for 2 years following the fire. There was little evidence that fire affected suspended‐sediment concentrations in the burned drainage. Sediment yields in subalpine streams may be less affected by fire than in lower elevation streams because of the slow release rate of water during spring snowmelt. Published in 2008 by John Wiley & Sons, Ltd.
Analysis of the water content in an unconfined aquifer with a partially penetrated pumping well
Authors: Chen Jiann‐Mou
Published: September 2008

Most methods developed to represent water flow phenomena in an unconfined aquifer with a fully penetrated pumping well are either numerical, such as the well‐known FEMWTER model, or experimental; analytical models of a partially penetrated pumping well are rare. This study employs the linearized Richards equation as the governing equation, with the aid of Fourier Integral Transformation, to obtain an analytical solution of the water content distribution in an unconfined aquifer with a partially penetrated pumping well. The results from this study could serve to substantiate in some sense results from numerical models. In addition, the theory developed herein can be modified to simulate a vacuum‐pressured pumping well since it is derived by considering, among others, the location and length of a well screen with fluxes. Copyright © 2008 John Wiley & Sons, Ltd.
Bone marrow stroma cells regulate TIEG1 expression in acute lymphoblastic leukemia cells: Role of TGFβ/BMP‐6 and TIEG1 in chemotherapy escape
Authors: Døsen‐Dahl Guri , Munthe Else , Nygren Marit Kveine , Stubberud Heidi , Hystad Marit E. , Rian Edith
Published: September 2008

The bone marrow microenvironment regulates early B lymphopoiesis and protects leukemia cells against chemotherapy treatment, thus the microenvironment may serve as a sanctuary site for these cells. Yet, few factors that contribute to this process are known. We have explored the role of transforming growth factor β (TGFβ) and bone morphogenetic protein‐6 (BMP‐6) and one target gene, TGFβ inducible early gene 1 (TIEG1), in the communication between stroma cells and acute lymphoblastic leukemia (ALL) cell lines and their escape from chemotherapy. Here, we have demonstrated TIEG1 expression in both normal B progenitor cells and ALL cells, which increased rapidly upon TGFβ and BMP‐6 treatment. Stimulation with TGFβ or BMP‐6, as well as overexpression of TIEG1 inhibited proliferation. Furthermore, interaction with stroma cells induced TIEG1 expression in ALL cells, inhibited their proliferation and protected the cells against chemotherapeutic treatment. Similarly, treatment with TGFβ or BMP‐6, as well as overexpression of TIEG1, protected ALL cells against chemotherapy‐induced cell death. These data suggest that TGFβ and BMP‐6 in the bone marrow microenvironment allow leukemia cells to escape therapy. Further, the data indicate that TIEG1 might be involved in mediating this effect from the microenvironment onto the leukemia cells. © 2008 Wiley‐Liss, Inc.
Genetic polymorphisms in the MMP‐7 gene and breast cancer survival
Authors: Beeghly‐Fadiel Alicia , Shu Xiao‐ou , Long Jirong , Li Chun , Cai Qiuyin , Cai Hui , Gao Yu‐Tang , Zheng Wei
Published: September 2008

Matrix metalloproteinase‐7 (MMP‐7) is a small secreted proteolytic enzyme with broad substrate specificity. Its expression has been shown to be associated with tumor invasion, metastasis and survival for a variety of cancers. We systematically evaluated single nucleotide polymorphisms (SNPs) in MMP‐7 in relation to breast cancer survival in a large follow‐up study. Included were 1,079 breast cancer cases that were recruited from 1996 to 1998 and followed for a median of 7.1 years as part of the Shanghai Breast Cancer Study (SBCS). Eleven SNPs, including 2 known functional promoter SNPs, were analyzed using the Affymetrix Targeted Genotyping System. Associations with survival were evaluated by Cox proportional hazards regression and Kaplan‐Meier functions. Statistically significant associations with disease‐free and/or overall survival (OS) were found for 5 polymorphisms; these associations were explained primarily by 2 SNPs (rs11568818 and rs11225297) that were in high linkage disequilibrium (LD) with the others. Patients homozygous for the rs11568818 rare allele (G) had a significantly worse prognosis (OS HR: 6.7, 95% CI: 2.4–18.6) than patients homozygous for the common allele (A). Significantly improved survival was seen for patients with the rs11225297 T allele, and this association occurred in a dose‐response manner; patients with AT (OS HR: 0.7, 95% CI: 0.5–0.9) and TT (OS HR: 0.3, 95% CI: 0.1–0.8) fared better than patients with AA (p‐value for trend: 0.001). Thus, common MMP‐7 genetic polymorphisms were found to be significant determinants of survival among Chinese women with breast cancer. © 2008 Wiley‐Liss, Inc.
Antiadult T‐cell leukemia effects of brown algae fucoxanthin and its deacetylated product, fucoxanthinol
Authors: Ishikawa Chie , Tafuku Senji , Kadekaru Takashi , Sawada Shigeki , Tomita Mariko , Okudaira Taeko , Nakazato Tetsuro , Toda Takayoshi , Uchihara Jun‐Nosuke , Taira Naoya , Ohshiro Kazuiku , Yasumoto Takeshi , Ohta Takao , Mori Naoki
Published: September 2008

Adult T‐cell leukemia (ATL) is a fatal malignancy of T lymphocytes caused by human T‐cell leukemia virus type 1 (HTLV‐1) infection and remains incurable. Carotenoids are a family of natural pigments and have several biological functions. Among carotenoids, fucoxanthin is known to have antitumorigenic activity, but the precise mechanism of action is not elucidated. We evaluated the anti‐ATL effects of fucoxanthin and its metabolite, fucoxanthinol. Both carotenoids inhibited cell viability of HTLV‐1‐infected T‐cell lines and ATL cells, and fucoxanthinol was approximately twice more potent than fucoxanthin. In contrast, other carotenoids, β‐carotene and astaxanthin, had mild inhibitory effects on HTLV‐1‐infected T‐cell lines. Importantly, uninfected cell lines and normal peripheral blood mononuclear cells were resistant to fucoxanthin and fucoxanthinol. Both carotenoids induced cell cycle arrest during G1 phase by reducing the expression of cyclin D1, cyclin D2, CDK4 and CDK6, and inducing the expression of GADD45α, and induced apoptosis by reducing the expression of Bcl‐2, XIAP, cIAP2 and survivin. The induced apoptosis was associated with activation of caspase‐3, ‐8 and ‐9. Fucoxanthin and fucoxanthinol also suppressed IκBα phosphorylation and JunD expression, resulting in inactivation of nuclear factor‐κB and activator protein‐1. Mice with severe combined immunodeficiency harboring tumors induced by inoculation of HTLV‐1‐infected T cells responded to treatment with fucoxanthinol with suppression of tumor growth, showed extensive tissue distribution of fucoxanthinol, and the presence of therapeutically effective serum concentrations of fucoxanthinol. Our preclinical data suggest that fucoxanthin and fucoxanthinol could be potentially useful therapeutic agents for patients with ATL. © 2008 Wiley‐Liss, Inc.
Defining the molecular action of HDAC inhibitors and synergism with androgen deprivation in ERG‐positive prostate cancer
Authors: Björkman Mari , Iljin Kristiina , Halonen Pasi , Sara Henri , Kaivanto Elisa , Nees Matthias , Kallioniemi Olli P.
Published: September 2008

Gene fusions between prostate‐specific, androgen responsive TMPRSS2 gene and oncogenic ETS factors, such as ERG, occur in up to 50% of all prostate cancers. We recently defined a gene signature that was characteristic to prostate cancers with ERG activation. This suggested epigenetic reprogramming, such as upregulation of histone deactylase 1 (HDAC1) gene and downregulation of its target genes. We then hypothesized that patients with ERG‐positive prostate cancers may benefit from epigenetic therapy such as HDAC inhibition (HDACi), especially in combination with antiandrogens. Here, we exposed ERG‐positive prostate cancer cell lines to HDAC inhibitors Trichostatin A (TSA), MS‐275 and suberoylanilide hydroxamic acid (SAHA) with or without androgen deprivation. We explored the effects on cell phenotype, gene expression as well as ERG and androgen receptor (AR) signaling. When compared with 5 other prostate cell lines, ERG‐positive VCaP and DuCap cells were extremely sensitive to HDACi, in particular TSA, showing synergy with concomitant androgen deprivation increasing apoptosis. Both of the HDAC inhibitors studied caused repression of the ERG‐fusion gene, whereas the pan‐HDAC inhibitor TSA prominently repressed the ERG‐associated gene signature. Additionally, HDACi and flutamide caused retention of AR in the cytoplasm, indicating blockage of androgen signaling. Our results support the hypothesis that HDACi, especially in combination with androgen deprivation, is effective against TMPRSS2‐ERG‐fusion positive prostate cancer in vitro. Together with our previous in vivo observations of an “epigenetic reprogramming gene signature” in clinical ERG‐positive prostate cancers, these studies provide mechanistic insights to ERG‐associated tumorigenesis and suggest therapeutic paradigms to be tested in vivo. © 2008 Wiley‐Liss, Inc.
Sensitivity to the non‐COX inhibiting celecoxib derivative, OSU03012, is p21WAF1/CIP1 dependent
Authors: Ding Haiming , Han Chunhua , Guo Dongmei , Wang Dasheng , Duan Wenrui , Chen Ching‐Shih , D'Ambrosio Steven M.
Published: September 2008

OSU03012 is a non‐COX inhibiting celecoxib derivative with growth inhibiting and apoptotic activity in many cancer cell lines. To investigate mechanisms related to cell cycle proteins in growth inhibition and apoptosis induced by OSU03012, the primary human oral epithelial cell line, TE1177, was transformed with HPV16 E6 (TE/E6), HPV16 E7 (TE/E7) or empty vector (TE/V). TE/E6 cell lines exhibiting low levels of p53 and undetectable levels of p21WAF1/CIP1 were sensitized to the growth inhibiting and apoptotic effects of OSU03012. The TE/E7 cell lines expressing low levels of Rb and elevated levels of p53 and p21WAF1/CIP1 were resistant. OSU03012 reduced the number of cells in the S phase of the TE/E7 and TE/V cell lines with intact p53‐p21WAF1/CIP1 checkpoint, but not in the checkpoint defective TE/E6 cell lines. Treatment with OSU03012 also markedly reduced the levels of cyclin A and Cdk2 in TE/E7 and TE/V, but not in TE/E6 cell lines, which had significantly enhanced basal levels of cyclin A and Cdk2. Consistent with the TE/E6 cell line, p21WAF1/CIP1−/− mouse embryo fibroblasts were more sensitive to OSU03012‐induced apoptosis as evidenced by PARP and caspase 3 cleavages. These data suggest that p21WAF1/CIP1 is an important factor in the sensitivity of cells to the growth inhibiting and apoptotic effects of OSU03012. © 2008 Wiley‐Liss, Inc.
OSU03012 activates Erk1/2 and Cdks leading to the accumulation of cells in the S‐phase and apoptosis
Authors: Ding Haiming , Han Chunhua , Guo Dongmei , Wang Dasheng , Chen Ching‐Shih , D'Ambrosio Steven M.
Published: September 2008

OSU03012, a Celecoxib derivative, has been shown to inhibit proliferation and induce apoptosis in human cancer cell lines. However, its underlying mechanisms are not completely understood. In our study, the relationship between cell cycle inhibition and apoptosis induced by OSU03012 was investigated in human oral cancer cell lines. In the premalignant and malignant cell lines, OSU03012‐induced growth inhibition, S‐phase arrest, and apoptosis were accompanied by a marked increase in the activity of Erk1/2 and Cdk2/cyclin A. Inhibition of Cdks by roscovitine partially blocked OSU03012‐induced growth inhibition and apoptosis. Although the activity of cdc2/cyclin B was reduced, expression of constructively active cdc2AF did not reverse OSU03012‐induced S‐phase arrest. When Erk1/2 was inhibited by U0126 before addition of OSU03012, growth inhibition and apoptosis induced by OSU03012 were attenuated. The levels of the Cdk2/cyclin A were reduced and cells accumulated in the G0/G1 phase. When cells were allowed to accumulate in S‐phase before addition of U0126, apoptosis also was attenuated suggesting that Erk1/2 is required for both progression of cells into the S‐phase and apoptosis. Expression of constructively active MEK enhanced OSU03012‐induced apoptosis. OSU03012 selectively inhibited the proliferation in premalignant and malignant, but not normal human oral cell lines. In conclusion, we show that OSU03012 has potent anti‐proliferative and apoptotic activity against premalignant and malignant human oral cells through activation of Erk1/2, and Cdks. OSU0312 may provide unique opportunities for cancer prevention and sensitization of cancer cells to S‐phase modalities. © 2008 Wiley‐Liss, Inc.
Estrogen alpha and progesterone receptor expression in the normal mammary epithelium in relation to breast cancer risk
Authors: Lagiou Pagona , Georgila Christina , Samoli Evangelia , Lagiou Areti , Zourna Pantelina , Minaki Ploumitsa , Vassilarou Dorothy , Papadiamandis Ioannis , Sfikas Constantinos , Kalapothaki Victoria , Sekeris Constantine E. , Trichopoulos Dimitrios
Published: September 2008

Estrogens play a central role in the etiology of breast cancer, and results from observational studies and randomized trials have also implicated progestins. The effects of these hormones in the mammary tissue are exerted through binding with specific receptor proteins in the cell nucleus. It has been proposed that higher estrogen receptor alpha expression in the normal breast epithelium may increase breast cancer risk. In a study in Greece, we determined estrogen alpha and progesterone receptor expression in normal mammary tissue adjacent to the pathological tissue from 267 women with breast cancer and 299 women with benign breast disease. Mouse monoclonal antibodies specific for estrogen receptor alpha and progesterone receptor were applied. The H–index, which incorporates frequency and intensity of staining of the cells, and can range from 0 to 300, was deemed positive when it exceeded 9. Among premenopausal women, there was no evidence for an association with breast cancer risk for expression of either type of receptors. Among postmenopausal women, breast cancer risk was inversely associated with expression of both estrogen alpha (odds ratio (OR) = 0.39; p = 0.015) and progesterone (OR = 0.40; p = 0.008) receptors. The hypothesis that overexpression of estrogen receptors alpha or progesterone receptors in normal breast epithelium may increase the risk of breast cancer was not supported by our data. Instead, we found evidence that overexpression of these receptors may be associated with reduced risk for breast cancer in line with the well‐known association of expression of these receptors in the malignant tissue and better breast cancer prognosis. © 2008 Wiley‐Liss, Inc.
The head and neck muscles of the Philippine colugo (Dermoptera: Cynocephalus volans), with a comparison to tree‐shrews, primates, and other mammals
Authors: Diogo Rui
Published: September 2008

The colugos, or flying lemurs (Dermoptera), are arboreal gliding mammals that are commonly grouped with tree‐shrews (Scandentia) and Primates in the superorder Euarchonta. However, little is known about the head and neck muscles of these gliding mammals. This raises difficulties for the discussion of not only the functional morphology and evolution of colugos, but also the origin, evolution, functional morphology, and phylogenetic relationships of the Euarchonta as a whole, and thus also of our own clade, the Primates. In this work, I describe the head and neck muscles of the colugo Cynocephalus volans, and compare these muscles with those of other mammals, either dissected by me or described in the literature. My observations and comparisons indicate that, with respect to the number of muscles, the plesiomorphic condition for euarchontans as well as for primates is more similar to that found in extant tree‐shrews than in extant colugos. This is because various muscles that were probably plesiomorphically present in the euarchontan and primate clades, as, e.g., the stylohyoideus, mandibulo‐auricularis, cleido‐occipitalis, omohyoideus, and sternohyoideus, are not present as independent elements in extant colugos. These observations and comparisons also indicate that various laryngeal and facial muscles that are present in modern humans were absent in the last common ancestor of extant primates. J. Morphol., 2009. © 2008 Wiley‐Liss, Inc.
Inhibition by KMI‐574 leads to dislocalization of BACE1 from lipid rafts
Authors: Ebina Maiko , Futai Eugene , Tanabe Chiaki , Sasagawa Noboru , Kiso Yoshiaki , Ishiura Shoichi
Published: September 2008

BACE1 initiates processing of the amyloid precursor protein (APP) in the production of amyloid β (Aβ) peptide. After β‐cleavage by BACE1, the C‐terminal stub of the APP fragment is further processed by the γ‐secretase complex to produce Aβ. Because APP, Aβ, the γ‐secretase complex, and BACE1 are found in lipid raft membranes, Aβ production is widely accepted to occur in lipid rafts. However, whether BACE1 is activated within the rafts is unclear. To analyze the relationship between the activity and the localization of BACE1, we used a new BACE1 inhibitor, KMI‐574, and separated raft membranes on sucrose density gradients. In the presence of KMI‐574, the localization of BACE1 shifted from the rafts to nonraft membranes in HEK293 cells. We also analyzed the proteolytically inactive mutants, D93A, D289A, and D93A/D289A, of BACE1. These mutants also moved from rafts to nonrafts, and the D93A/D289A double‐mutant localized exclusively to nonraft membranes. The mutants were defective in maturation by glynosylation and formed hyperoligomers, suggesting that the BACE1 oligomers could not exit from the ER and be transported to the Golgi apparatus. Our findings suggest that the activated conformation of BACE1 is important for protein transport and localization to lipid rafts. © 2008 Wiley‐Liss, Inc.
Role for Rab3a in oligodendrocyte morphological differentiation
Authors: Anitei Mihaela , Cowan Ann E. , Pfeiffer Steven E. , Bansal Rashmi
Published: September 2008

Rab3a, a small GTPase important for exocytosis, is uniquely up‐regulated as oligodendrocytes enter terminal differentiation and initiate myelin biosynthesis. In this study, we analyze the role of this protein in oligodendrocyte morphological differentiation by using Rab3a overexpression and siRNAi‐mediated Rab3a silencing. We found that Rab3a silencing delayed mature oligodendrocyte morphological differentiation but did not interfere with lineage progression of OL progenitors; this is consistent with the high levels of Rab3a expressed by mature oligodendrocytes compared with progenitor cells. Overexpression of GTP‐bound, but not that of wild‐type, Rab3a delayed OL morphological differentiation; this suggests that expression of a GTP‐bound Rab3a mutant interferes with the normal function of endogenous Rab3a. We have also identified in oligodendrocytes two other exocytic small GTPases, Rab27B and RalA. Together, these findings indicate that Rab3a specifically stimulates morphological differentiation of mature oligodendrocytes and thus may be part of the necessary machinery for myelin membrane biogenesis. © 2008 Wiley‐Liss, Inc.
Enhancement of plant growth and decontamination of nickel‐spiked soil using PGPR
Authors: Tank Neelam , Saraf Meenu
Published: September 2008

Phytoremediation i.e. the use of plants to adsorb, accumulate or detoxify contaminants is an emerging area of interest. A viable technology needs optimum biomass production in metal contaminated soil. Five strains of microbes were selected after testing their potential as plant growth promoters, on the basis of their phosphate solubilization ability, IAA, siderophore and HCN production and biocontrol potentials. They were examined for growth in synthetic medium supplemented with nickel and their MIC (2 mM) was determined. These isolates were also able to grow and produce siderophores in presence of heavy metals like Ni, Zn and Cd. A positive response of bacterial inoculants was observed in chickpea plants towards toxic effect of nickel present in soil at different concentration (0, 1 and 2 mM). Bacterial inoculants enhanced fresh and dry weight of plants even at 2 mM nickel concentration. Pot experiments indicated that presence of nickel at upto 1 mM enhanced plant growth compared to uninoculated nickel free plants. The accumulation of nickel/plant was just 50% inPseudomonasinoculated plants as compared to uninoculated plants with 2 mM nickel concentration along with increased biomass. The results suggest the use of these PGPR to enhance plant growth in nickel‐spiked land and remediate nickel from contaminated sites. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Transcriptional and metabolic response in yeast Saccharomyces cerevisiae cells during polyethylene glycol‐dependent transformation
Authors: Kawai Shigeyuki , Phan Tuan Anh , Kono Emi , Harada Kazuo , Okai Chihiro , Fukusaki Eiichiro , Murata Kousaku
Published: September 2008

Intact cells of the yeast Saccharomyces cerevisiae were transformed with exogenous DNA by incubating the cells with plasmid in the presence of polyethylene glycol (PEG), which has been shown to be required, although the underlying has not been elucidated. In this study, we found that incubation of the S. cerevisiae cells with PEG was not only required for the PEG‐dependent transformation but also enhanced transformation, suggesting that PEG might cause an intracellular response. To understand the response, microarray and metabolome analyses were conducted. We found that incubation of the cells without PEG caused up‐regulation of several genes, including those which are involved in carbon source metabolisms, e.g. fatty acid metabolism, yielding acetyl‐CoA and those involved in stress‐response. Contrary to this, incubation of the cells with PEG gave no transcriptional change. These microarray data were supported by the results of metabolome analysis for anionic metabolites, implying that the physical effect of PEG on cell membrane, rather than the effect of PEG itself on the intracellular response, could cause high transformation in the PEG‐dependent transformation. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Characterization and utilization of a novel triflate ionic liquid stationary phase for use in comprehensive two‐dimensional gas chromatography
Authors: Reid Vanessa R. , Crank Jeffery A. , Armstrong Daniel W. , Synovec Robert E.
Published: September 2008

A novel triflate (trifluoromethylsulfonate) ionic liquid (IL) thin film (0.08 μm) stationary phase was implemented for use within the second column of a comprehensive GC×GC configuration. The first column in the configuration had a 5% phenyl/95% dimethyl polysiloxane (DMPS) stationary phase with a 0.4 μm film. The DMPS×IL column configuration was used to separate a mixture of 32 compounds of various chemical functional classes. The GC×GC results for the IL column were compared with a commercially available polar column (with a 0.1 μm PEG stationary phase film) used as the second column instead. Additional studies focused on the rapid and selective separation of four phosphorous–oxygen (P–O) containing compounds from the 32‐compound matrix: dimethyl methylphosphonate (DMMP), diethyl methylphosphonate (DEMP), diisopropyl methylphosphonate (DIMP), and triethyl phosphate (TEP). van't Hoff plots (plots of ln k vs. 1/T) demonstrated the difference in retention between the P–O containing compounds (with DMMP reported in detail) and other classes of compounds (i. e., 2‐pentanol and n‐dodecane as representative) using either the IL column or the commercial PEG column. The selectivity (α) of the triflate IL column and the commercially available PEG column were also compared. The IL column provided significantly larger selectivities between DMMP and the other two compounds (2‐pentanol and n‐dodecane) than the commercial PEG column. The α for DMMP relative to n‐dodecane was 3.0‐fold greater for the triflate IL column, and the α for DMMP relative to 2‐pentanol was 1.7‐fold greater for the triflate IL column than for the PEG column.
Use of partially porous column as second dimension in comprehensive two‐dimensional system for analysis of polyphenolic antioxidants
Authors: Dugo Paola , Cacciola Francesco , Herrero Miguel , Donato Paola , Mondello Luigi
Published: September 2008

In the present work, a comprehensive LC system using a microbore HPLC column in the first dimension and a partially porous column in the second dimension was developed and applied to the separation of polyphenolic components in a red wine sample. The performance of the partially porous short column (3.0 cm) was compared to that of a monolithic column, of comparable dimensions. The results obtained demonstrated the possibility to use partially porous columns to obtain fast analyses, using high flow rates, under repetitive gradient conditions and with very brief reconditioning times. A conventional HPLC system was used since the backpressure generated by the shell‐packed column, even at very high flow rates, was well within the operational limits. The use of an increased column temperature (60°C) allowed a further pressure‐drop decrease, with no stationary phase degradation, or loss in column performance.
Photodynamic therapy with intratumoral administration of Lipid‐Based mTHPC in a model of breast cancer recurrence
Authors: D'Hallewin Marie Ange , Kochetkov Dmitri , Viry‐Babel Yan , Leroux Agnes , Werkmeister Elisabeth , Dumas Dominique , Gräfe Susanna , Zorin Vladimir , Guillemin François , Bezdetnaya Lina
Published: September 2008

Background and Objectives

Generalized skin sensitization is a main drawback of photodynamic therapy with systemic administration of photosensitizers. We have evaluated the potential use of an intratumoral injection of a liposomal formulation of mTHPC (Foslip) in a mouse model of local recurrence of breast cancer.

Materials and Methods

Mice were directly injected into the tumor (IT) with 25 µl of a Foslip suspension (0.15 mg/ml) and illumination (652 nm, 20 J/cm2) was performed at different time points with pathological assessment after 48 hours. In a parallel mice series plasma samples were obtained at different endpoints after IT Foslip injection for HPLC analysis and the tumors were subjected in toto to macrofluorescence imaging. Fluorescence polarization measurements were conducted in vitro to estimate the rate of sensitizer redistribution from liposomes.

Results

Optimal, albeit partial, cure rates were obtained at 24 hours post‐sensitizer and uninistration. Inhomogeneous and weak fluorescence was observed at early time points and became maximal at 24 hours. Plasma levels of mTHPC increased until 15 hours. Fluorescence polarization measurements showed a slow sensitizer transfer from liposomes to model membranes.

Discussion and Conclusion

The weak intratumoral fluorescence at early time points could be explained by concentration quenching within the liposomes as evidenced from fluorescence polarization studies. Progressive mTHPC redistribution from liposomes and its further incorporation into tumor tissue resulted in fluorescence build‐up over time with a maximum at 24 hours post‐injection. This correlates perfectly with the best therapeutic effect at this time point. The absence of total cure can be attributed to inhomogeneous photosensitizer distribution. mTHPC is reabsorbed into the blood stream but the total administered amount is much reduced as opposed to systemic administration so that repeated PDT sessions might be favorable in terms of side effects and tumor response. Lesers Surg. Med. 40:543–549, 2008. © 2008 Wiley‐Liss, Inc.