bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractAdult 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

AbstractGene 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

AbstractOSU03012 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

AbstractOSU03012, 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

AbstractEstrogens 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

AbstractThe 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

AbstractBACE1 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

AbstractRab3a, 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

AbstractPhytoremediation 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

AbstractIntact 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

AbstractA 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

AbstractIn 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

AbstractBackground and ObjectivesGeneralized 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 MethodsMice 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.ResultsOptimal, 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 ConclusionThe 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.