The Experts below are selected from a list of 3912 Experts worldwide ranked by ideXlab platform
Maria T. Berciano - One of the best experts on this subject based on the ideXlab platform.
-
Nuclear organization and dynamics of transcription sites in rat sensory ganglia neurons detected by incorporation of 5′-Fluorouridine into nascent RNA
Neuroscience, 2006Co-Authors: Iñigo Casafont, Joaquín Navascués, Emma Pena, Miguel Lafarga, Maria T. BercianoAbstract:In this study we have used the transcription assay with 5'-Fluorouridine incorporation into nascent RNA to analyze the nuclear organization and dynamics of transcription sites in rat trigeminal ganglia neurons. The 5'-FU administrated by i.p. injection was successfully incorporated into nuclear domains containing actively transcribing genes of trigeminal neurons. 5'-Fluorouridine RNA-labeling was detected with immunocytochemistry at light and electron microscopy levels. The 5'-Fluorouridine incorporation sites were detected in the nucleolus, particularly on the dense fibrillar component, and in numerous transcription foci spread throughout the euchromatin regions, without preferential positioning at the nuclear periphery or in the nuclear interior. Double labeling experiments to combine 5'-Fluorouridine incorporation with molecular markers of nuclear compartments showed the absence of transcription sites in Cajal bodies and nuclear speckles of splicing factors. Similarly, no 5'-Fluorouridine labeling was detected in well-characterized chromatin silencing domain, the telomeric heterochromatin. The specificity and sensitivity of the run-on transcription assay in trigeminal ganglia neurons was verified by the i.p. administration of the transcription inhibitor actinomycin D. The dramatic reduction in RNA synthesis upon actinomycin D treatment was associated with two important cellular events, heterochromatin silencing and formation of DNA damage/repair nuclear foci, demonstrated by the expression of tri-methylated histone H4 and phosphorylated H2AX, respectively. 5'-Fluorouridine incorporation in animal models provides a useful tool to investigate the organization of gene expression in mammalian neurons in both normal physiology and experimental pathology systems.
-
nuclear organization and dynamics of transcription sites in rat sensory ganglia neurons detected by incorporation of 5 Fluorouridine into nascent rna
Neuroscience, 2006Co-Authors: Iñigo Casafont, Joaquín Navascués, Emma Pena, Miguel Lafarga, Maria T. BercianoAbstract:In this study we have used the transcription assay with 5'-Fluorouridine incorporation into nascent RNA to analyze the nuclear organization and dynamics of transcription sites in rat trigeminal ganglia neurons. The 5'-FU administrated by i.p. injection was successfully incorporated into nuclear domains containing actively transcribing genes of trigeminal neurons. 5'-Fluorouridine RNA-labeling was detected with immunocytochemistry at light and electron microscopy levels. The 5'-Fluorouridine incorporation sites were detected in the nucleolus, particularly on the dense fibrillar component, and in numerous transcription foci spread throughout the euchromatin regions, without preferential positioning at the nuclear periphery or in the nuclear interior. Double labeling experiments to combine 5'-Fluorouridine incorporation with molecular markers of nuclear compartments showed the absence of transcription sites in Cajal bodies and nuclear speckles of splicing factors. Similarly, no 5'-Fluorouridine labeling was detected in well-characterized chromatin silencing domain, the telomeric heterochromatin. The specificity and sensitivity of the run-on transcription assay in trigeminal ganglia neurons was verified by the i.p. administration of the transcription inhibitor actinomycin D. The dramatic reduction in RNA synthesis upon actinomycin D treatment was associated with two important cellular events, heterochromatin silencing and formation of DNA damage/repair nuclear foci, demonstrated by the expression of tri-methylated histone H4 and phosphorylated H2AX, respectively. 5'-Fluorouridine incorporation in animal models provides a useful tool to investigate the organization of gene expression in mammalian neurons in both normal physiology and experimental pathology systems.
Iñigo Casafont - One of the best experts on this subject based on the ideXlab platform.
-
Nuclear organization and dynamics of transcription sites in rat sensory ganglia neurons detected by incorporation of 5′-Fluorouridine into nascent RNA
Neuroscience, 2006Co-Authors: Iñigo Casafont, Joaquín Navascués, Emma Pena, Miguel Lafarga, Maria T. BercianoAbstract:In this study we have used the transcription assay with 5'-Fluorouridine incorporation into nascent RNA to analyze the nuclear organization and dynamics of transcription sites in rat trigeminal ganglia neurons. The 5'-FU administrated by i.p. injection was successfully incorporated into nuclear domains containing actively transcribing genes of trigeminal neurons. 5'-Fluorouridine RNA-labeling was detected with immunocytochemistry at light and electron microscopy levels. The 5'-Fluorouridine incorporation sites were detected in the nucleolus, particularly on the dense fibrillar component, and in numerous transcription foci spread throughout the euchromatin regions, without preferential positioning at the nuclear periphery or in the nuclear interior. Double labeling experiments to combine 5'-Fluorouridine incorporation with molecular markers of nuclear compartments showed the absence of transcription sites in Cajal bodies and nuclear speckles of splicing factors. Similarly, no 5'-Fluorouridine labeling was detected in well-characterized chromatin silencing domain, the telomeric heterochromatin. The specificity and sensitivity of the run-on transcription assay in trigeminal ganglia neurons was verified by the i.p. administration of the transcription inhibitor actinomycin D. The dramatic reduction in RNA synthesis upon actinomycin D treatment was associated with two important cellular events, heterochromatin silencing and formation of DNA damage/repair nuclear foci, demonstrated by the expression of tri-methylated histone H4 and phosphorylated H2AX, respectively. 5'-Fluorouridine incorporation in animal models provides a useful tool to investigate the organization of gene expression in mammalian neurons in both normal physiology and experimental pathology systems.
-
nuclear organization and dynamics of transcription sites in rat sensory ganglia neurons detected by incorporation of 5 Fluorouridine into nascent rna
Neuroscience, 2006Co-Authors: Iñigo Casafont, Joaquín Navascués, Emma Pena, Miguel Lafarga, Maria T. BercianoAbstract:In this study we have used the transcription assay with 5'-Fluorouridine incorporation into nascent RNA to analyze the nuclear organization and dynamics of transcription sites in rat trigeminal ganglia neurons. The 5'-FU administrated by i.p. injection was successfully incorporated into nuclear domains containing actively transcribing genes of trigeminal neurons. 5'-Fluorouridine RNA-labeling was detected with immunocytochemistry at light and electron microscopy levels. The 5'-Fluorouridine incorporation sites were detected in the nucleolus, particularly on the dense fibrillar component, and in numerous transcription foci spread throughout the euchromatin regions, without preferential positioning at the nuclear periphery or in the nuclear interior. Double labeling experiments to combine 5'-Fluorouridine incorporation with molecular markers of nuclear compartments showed the absence of transcription sites in Cajal bodies and nuclear speckles of splicing factors. Similarly, no 5'-Fluorouridine labeling was detected in well-characterized chromatin silencing domain, the telomeric heterochromatin. The specificity and sensitivity of the run-on transcription assay in trigeminal ganglia neurons was verified by the i.p. administration of the transcription inhibitor actinomycin D. The dramatic reduction in RNA synthesis upon actinomycin D treatment was associated with two important cellular events, heterochromatin silencing and formation of DNA damage/repair nuclear foci, demonstrated by the expression of tri-methylated histone H4 and phosphorylated H2AX, respectively. 5'-Fluorouridine incorporation in animal models provides a useful tool to investigate the organization of gene expression in mammalian neurons in both normal physiology and experimental pathology systems.
Yoshio Kaku - One of the best experts on this subject based on the ideXlab platform.
-
Novel lowly immunosuppressive antitumor Fluorouridine derivative, UK-21 : antitumor activity and effect on humoral immune response in mice.
Cancer chemotherapy and pharmacology, 1994Co-Authors: Hiroshi Mori, Ken-ichi Nakayama, Hiroichi Nagai, Akihide Koda, Daishirou Maeda, Jun-ichirou Kita, Yoshio KakuAbstract:Our previous studies indicated that a newly synthesized 5-Fluorouridine derivative, 2′,3′,5′- tris-O-[N-(2-n-propyl-n-pentanoyl)glycyl]-5-Fluorouridine (UK-21), revealed its antitumor activity by being converted to 5-Fluorouridine (5-FUR) and showed a low level of immunological side effects. However, the bioavailability of UK-21 given orally did not seem to be good. In the present study, we focused on the antitumor and immunosuppressive activities of UK-21 given i.p. to mice. UK-21 suppressed the growth of L-1210, P388 and EL4 leukemias inoculated i.v. into corresponding syngeneic mice and both the growth of Lewis lung carcinoma transplanted s.c. and its subsequent metastasis to the lung. UK-21 showed antitumor activity at doses almost 10 times lower than those of 5-fluorouracil (5-FU). The side effects of UK-21, especially on immune functions, were examined in comparison with those of 5-FUR, 5-FU, and cyclophosphamide (CY) at doses producing comparable antitumor activity. The suppressive effect of UK-21 on IgM and IgG antibody formation in mice immunized with ovalbumin was clearly weaker than that of 5-FUR, 5-FU, and CY. The suppressive effect of UK-21 on thymus weight was markedly weaker than that of 5-FU and CY. The reduction of WBC counts induced by UK-21 was also lower than that produced by any other agent. The results reported herein suggest the strong possibility of UK-21 being developed as a novel anticancer drug with cytotoxic mechanisms different from those of 5-FU. Our study also points to the chemical modification of 5-FUR as a feasible way of developing new anticancer drugs.
Wen-yong Lou - One of the best experts on this subject based on the ideXlab platform.
-
Efficient enzymatic regioselective benzoylation of 5-Fluorouridine catalysed by Novozym 435
Journal of Chemical Technology & Biotechnology, 2008Co-Authors: Min-hua Zong, Wen-yong LouAbstract:BACKGROUND: This work focuses on developing a mild, efficient and regioselective enzymatic procedure to synthesise 5′-O-benzoyl-5-Fluorouridine, a more powerful antitumour drug than 5-Fluorouridine itself, and examining the influences of several key variables on the reaction. RESULTS: The enzymatic regioselective benzoylation of 5-Fluorouridine can be successfully conducted with Novozym 435. The end-product was confirmed to be 5′-O-benzoyl-5-Fluorouridine by 13C nuclear magnetic resonance analysis. A co-solvent mixture of hexane and tetrahydrofuran (THF) (50:50 v/v) was found to be the best reaction medium. The optimal initial water activity, molar ratio of vinyl benzoate to 5-Fluorouridine and reaction temperature were 0.07, 25:1 and 70 °C respectively. Under the optimised conditions the initial reaction rate, substrate conversion and regioselectivity were found to be 32.8 mmol L−1 h−1, 98.9% and > 99% respectively. In addition, Novozym 435 still maintained 88.2% of its original activity even after being reused for ten batches at 70 °C, indicating excellent thermal and operational stability of the enzyme in the co-solvent mixture of hexane and THF. CONCLUSION: The results clearly show that the Novozym 435-catalysed regioselective benzoylation of 5-Fluorouridine is a novel and facile route for efficient preparation of 5′-O-benzoyl-5-Fluorouridine with potential antitumour activity. Copyright © 2008 Society of Chemical Industry
-
Novel and highly regioselective route for synthesis of 5-Fluorouridine lipophilic ester derivatives by lipozyme TL IM
Journal of Biotechnology, 2007Co-Authors: Huai Wang, Min-hua Zong, Wen-yong LouAbstract:Abstract For the first time, lipozyme TL IM, an inexpensive lipase from Thermomyces lanuginosa, was successfully applied to the regioselective synthesis of lipophilic 5-Fluorouridine ester derivatives. The ESI-MS and 13C NMR analysis confirmed that the end products of the acylation were 5′-O-acyl 5-Fluorouridines, more powerful anti-tumor drugs than 5-Fluorouridine itself. Notably, the chain length of acyl donors had an obvious effect on the initial rate and the maximum substrate conversion of the regioselective acylation. The acylation of 5-Fluorouridine with vinyl laurate was used as a model to explore the influence of various factors on the reaction with respect to the initial rate, the maximum substrate conversion and the regioselectivity. The optimum water activity, the molar ratio of vinyl laurate to 5-Fluorouridine, reaction temperature and shaking rate were 0.07, 15/1, 45 °C and 200 rpm, respectively, under which the maximum substrate conversion and the regioselectivity were as high as 98.4 and >99%, respectively, after a reaction time of around 6 h.
Akira Matsuda - One of the best experts on this subject based on the ideXlab platform.
-
nucleosides and nucleotides cxxxvii antitumor phospholipids with 5 Fluorouridine as a cytotoxic polar head synthesis of 5 phosphatidyl 5 Fluorouridines by phospholipase d catalyzed transphosphatidylation
Bioorganic & Medicinal Chemistry, 1995Co-Authors: Satoshi Shuto, Hiromichi Itoh, Atsushi Sakai, Keishi Nakagami, Shigeyuki Imamura, Akira MatsudaAbstract:5'-Phosphatidyl-5-Fluorouridines, with the same backbone structure as that of natural phospholipids, in which a polar-head group of usual phospholipids is replaced by 5-Fluorouridine, were designed to be potent antitumor agents. 5'-Phosphatidyl-5-Fluorouridines with a variety of diacyl or dialkyl residues in the glycerol moiety, were synthesized by phospholipase D-catalyzed transphosphatidylation from the corresponding phosphatidylcholine and 5-Fluorouridine. These new compounds were evaluated in mice with experimental tumors by ip and po administration. Dipalmitoyl and distearoyl derivatives 1b and 1c had the greatest antitumor activity against both P388 leukemia and Meth A fibrosarcoma in mice.
-
Nucleosides and nucleotides—CXXXVII. Antitumor phospholipids with 5-Fluorouridine as a cytotoxic polar-head: Synthesis of 5′-phosphatidyl-5-Fluorouridines by phospholipase d-catalyzed transphosphatidylation
Bioorganic & medicinal chemistry, 1995Co-Authors: Satoshi Shuto, Hiromichi Itoh, Atsushi Sakai, Keishi Nakagami, Shigeyuki Imamura, Akira MatsudaAbstract:Abstract 5′-Phosphatidyl-5-Fluorouridines, with the same backbone structure as that of natural phospholipids, in which a polar-head group of usual phospholipids is replaced by 5-Fluorouridine, were designed to be potent antitumor agents. 5′-Phosphatidyl-5-Fluorouridines with a variety of diacyl or dialkyl residues in the glycerol moiety, were synthesized by phospholipase D-catalyzed transphosphatidylation from the corresponding phosphatidylcholine and 5-Fluorouridine. These new compounds were evaluated in mice with experimental tumors by ip and po administration. Dipalmitoyl and distearoyl derivatives 1b and 1c had the greatest antitumor activity against both P388 leukemia and Meth A fibrosarcoma in mice.