The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Philippe Coucke - One of the best experts on this subject based on the ideXlab platform.
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the Ribonucleoside Diphosphate Reductase inhibitor e 2 deoxy fluoromethylene cytidine as a cytotoxic radiosensitizer in vitro
Cancer Research, 1999Co-Authors: Philippe Coucke, Laurent A Decosterd, E Cottin, Xiaoguang Chen, Linquan Sun, Sabine Stern, Nicolas Paschoud, Juliana DenekampAbstract:(E)-2′-Deoxy-(fluoromethylene)cytidine (FMdC) is known as an inhibitor of Ribonucleoside Diphosphate Reductase, a key enzyme in the de novo pathway of DNA synthesis. FMdC was tested as a modifier of radiation response in vitro on a human colon carcinoma cell line (WiDr), and the observed radiosensitization was confirmed on two human cervix cancer cell lines (C33-A and SiHa). Using the clonogenic assay, the effect ratio (ER) at a clinically relevant dose level of 2 Gy was 2.10 (50 nm FMdC), 1.70 (30 nm FMdC), and 1.71 (40 nm FMdC) for the three cell lines WiDr, C33-A, and SiHa, respectively. A more detailed analysis of the importance of timing and concentration of FMdC was done on the WiDr cell line alone, yielding an increased ER(2Gy) with increasing concentration and duration of exposure to the drug, ranging from 1.0 (6 h) to 1.8 (72 h) at 30 nm FMdC and from 1.2 (6 h) to 3.5 (24 h) at 300 nm. We investigated the effect of FMdC on the cellular deoxynucleotide triphosphate pool in WiDr cells and demonstrated a marked depletion of dATP and a significant rise of TTP levels. Cell cycle analysis showed early S-phase accumulation induced by FMdC alone, G2-M block induced by irradiation alone, and an increased accumulation of cells in G2-M if both modalities are used. Our data suggest that FMdC is a radiation response modifier in vitro on different cancer cell lines. The observed radiosensitization may in part be explained by alteration of the deoxynucleotide triphosphate pool, which is consistent with the effect of FMdC on Ribonucleoside Diphosphate Reductase.
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antitumor and radiosensitizing effects of e 2 deoxy 2 fluoromethylene cytidine a novel inhibitor of Ribonucleoside Diphosphate Reductase on human colon carcinoma xenografts in nude mice
Cancer Research, 1997Co-Authors: Linquan Sun, Louis Guillou, Reneolivier Mirimanoff, Philippe CouckeAbstract:Antitumor and radiosensitizing effects of (E)-2'-deoxy-2'-(fluromethylene) cytidine (FMdC), a novel inhibitor of ribonucleotide Reductase, were evaluated on nude mice bearing s.c. xenografts and liver metastases of a human colon carcinoma. FMdC given once daily or twice weekly has a dose-dependent antitumor effect. The maximum tolerated dose in the mice was reached with 10 mg/kg applied daily over 12 days. Twice weekly administration of FMdC reduced its toxicity but lowered the antitumor effect. Treatment of preestablished liver micrometastases obtained via intrasplenic injection of tumor cells, with 5 or 10 mg/kg FMdC, significantly prolonged the survival of the mice as compared to controls (P < 0.025 and P < 0.001, respectively). Ten mg/kg resulted in longer survival than 5 mg/kg FMdC (P < 0.05). Radiotherapy alone of s.c. xenografts (10 fractions over 12 days) yielded the radiation dose required to produce local tumor control in 50% of the treated mice (TCD50) of 43.0 Gy. When combined with FMdC, TCD50 was reduced to 22.5 and 19.0 Gy at doses of 5 and 10 mg/kg given i.p. 1 h before each irradiation, respectively. The corresponding enhancement ratios were 1.91 and 2.43, respectively. FMdC produced moderate and reversible myelosuppression. When 5 mg/kg FMdC was combined with irradiation, there was no increased skin or hematological toxicity as compared to radiotherapy or FMdC alone. At the 10 mg/kg level, however, lower leukocyte counts were observed. These results show that FMdC appears to be a potent anticancer drug and radiosensitizer.
Linquan Sun - One of the best experts on this subject based on the ideXlab platform.
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the Ribonucleoside Diphosphate Reductase inhibitor e 2 deoxy fluoromethylene cytidine as a cytotoxic radiosensitizer in vitro
Cancer Research, 1999Co-Authors: Philippe Coucke, Laurent A Decosterd, E Cottin, Xiaoguang Chen, Linquan Sun, Sabine Stern, Nicolas Paschoud, Juliana DenekampAbstract:(E)-2′-Deoxy-(fluoromethylene)cytidine (FMdC) is known as an inhibitor of Ribonucleoside Diphosphate Reductase, a key enzyme in the de novo pathway of DNA synthesis. FMdC was tested as a modifier of radiation response in vitro on a human colon carcinoma cell line (WiDr), and the observed radiosensitization was confirmed on two human cervix cancer cell lines (C33-A and SiHa). Using the clonogenic assay, the effect ratio (ER) at a clinically relevant dose level of 2 Gy was 2.10 (50 nm FMdC), 1.70 (30 nm FMdC), and 1.71 (40 nm FMdC) for the three cell lines WiDr, C33-A, and SiHa, respectively. A more detailed analysis of the importance of timing and concentration of FMdC was done on the WiDr cell line alone, yielding an increased ER(2Gy) with increasing concentration and duration of exposure to the drug, ranging from 1.0 (6 h) to 1.8 (72 h) at 30 nm FMdC and from 1.2 (6 h) to 3.5 (24 h) at 300 nm. We investigated the effect of FMdC on the cellular deoxynucleotide triphosphate pool in WiDr cells and demonstrated a marked depletion of dATP and a significant rise of TTP levels. Cell cycle analysis showed early S-phase accumulation induced by FMdC alone, G2-M block induced by irradiation alone, and an increased accumulation of cells in G2-M if both modalities are used. Our data suggest that FMdC is a radiation response modifier in vitro on different cancer cell lines. The observed radiosensitization may in part be explained by alteration of the deoxynucleotide triphosphate pool, which is consistent with the effect of FMdC on Ribonucleoside Diphosphate Reductase.
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The Ribonucleoside Diphosphate Reductase inhibitor (E)-2�-deoxy-(fluoromethylene)cytidine as a cytotoxic radiosensitizer in vitro
1999Co-Authors: Laurent A Decosterd, E Cottin, Xiaoguang Chen, Linquan Sun, Sabine Stern, Nicolas Paschoud, Juliana DenekampAbstract:(E)-2*-Deoxy-(fluoromethylene)cytidine (FMdC) is known as an inhib-itor of Ribonucleoside Diphosphate Reductase, a key enzyme in the de novo pathway of DNA synthesis. FMdC was tested as a modifier of radiation response in vitro on a human colon carcinoma cell line (WiDr), and the observed radiosensitization was confirmed on two human cervix cancer cell lines (C33-A and SiHa). Using the clonogenic assay, the effect ratio (ER) at a clinically relevant dose level of 2 Gy was 2.10 (50 nM FMdC), 1.70 (30 nM FMdC), and 1.71 (40 nM FMdC) for the three cell lines WiDr, C33-A, and SiHa, respectively. A more detailed analysis of the importance of timing and concentration of FMdC was done on the WiDr cell line alone, yielding an increased ER(2Gy) with increasing concentration and duration of exposure to the drug, ranging from 1.0 (6 h) to 1.8 (72 h) at 30 nM FMdC and from 1.2 (6 h) to 3.5 (24 h) at 300 nM. We investigated the effect of FMdC on the cellular deoxynucleotide triphosphate pool in WiDr cells and demonstrated a marked depletion of dATP and a significant rise of TTP levels. Cell cycle analysis showed early S-phase accumulation induced by FMdC alone, G2-M block induced by irradiation alone, and an increased accumulation of cells in G2-M if both modalities are used. Our data suggest that FMdC is a radiation response modifier in vitro on different cancer cell lines. The observed radiosensitization may in part be explained by alteration of the deoxynucleotide triphosphate pool, which is consistent with the effect of FMdC on Ribonucleoside Diphosphate reduc-tase
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antitumor and radiosensitizing effects of e 2 deoxy 2 fluoromethylene cytidine a novel inhibitor of Ribonucleoside Diphosphate Reductase on human colon carcinoma xenografts in nude mice
Cancer Research, 1997Co-Authors: Linquan Sun, Louis Guillou, Reneolivier Mirimanoff, Philippe CouckeAbstract:Antitumor and radiosensitizing effects of (E)-2'-deoxy-2'-(fluromethylene) cytidine (FMdC), a novel inhibitor of ribonucleotide Reductase, were evaluated on nude mice bearing s.c. xenografts and liver metastases of a human colon carcinoma. FMdC given once daily or twice weekly has a dose-dependent antitumor effect. The maximum tolerated dose in the mice was reached with 10 mg/kg applied daily over 12 days. Twice weekly administration of FMdC reduced its toxicity but lowered the antitumor effect. Treatment of preestablished liver micrometastases obtained via intrasplenic injection of tumor cells, with 5 or 10 mg/kg FMdC, significantly prolonged the survival of the mice as compared to controls (P < 0.025 and P < 0.001, respectively). Ten mg/kg resulted in longer survival than 5 mg/kg FMdC (P < 0.05). Radiotherapy alone of s.c. xenografts (10 fractions over 12 days) yielded the radiation dose required to produce local tumor control in 50% of the treated mice (TCD50) of 43.0 Gy. When combined with FMdC, TCD50 was reduced to 22.5 and 19.0 Gy at doses of 5 and 10 mg/kg given i.p. 1 h before each irradiation, respectively. The corresponding enhancement ratios were 1.91 and 2.43, respectively. FMdC produced moderate and reversible myelosuppression. When 5 mg/kg FMdC was combined with irradiation, there was no increased skin or hematological toxicity as compared to radiotherapy or FMdC alone. At the 10 mg/kg level, however, lower leukocyte counts were observed. These results show that FMdC appears to be a potent anticancer drug and radiosensitizer.
Gholamreza Darai - One of the best experts on this subject based on the ideXlab platform.
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analysis of the first complete dna sequence of an invertebrate iridovirus coding strategy of the genome of chilo iridescent virus
Virology, 2001Co-Authors: Nurith J Jakob, Kristin Muller, Udo Bahr, Gholamreza DaraiAbstract:Abstract Chilo iridescent virus (CIV), the type species of the genus Iridovirus, a member of the Iridoviridae family, is highly pathogenic for a variety of insect larvae. The virions contain a single linear ds DNA molecule that is circularly permuted and terminally redundant. The coding capacity and strategy of the CIV genome was elucidated by the analysis of the complete DNA nucleotide sequence of the viral genome (212,482 bp) using cycle sequencing by primer walking technology. Both DNA strands were sequenced independently and the average redundancy for each nucleotide was found to be 1.85. The base composition of the viral genomic DNA sequence was found to be 71.37% A+T and 28.63% G+C. The CIV genome contains 468 open reading frames (ORFs). The size of the individual viral gene products ranges between 40 and 2432 amino acids. The analysis of the coding capacity of the CIV genome revealed that 50% (234 ORFs) of all identified ORFs were nonoverlapping. The comparison of the deduced amino acid sequences to entries in protein data banks led to the identification of several genes with significant homologies, such as the two major subunits of the DNA-dependent RNA polymerase, DNA polymerase, protein kinase, thymidine and thymidylate kinase, thymidylate synthase, Ribonucleoside-Diphosphate Reductase, major capsid protein, and others. The highest homologies were detected between putative viral gene products of CIV and lymphocystis disease virus of fish (LCDV). Although many CIV putative gene products showed significant homologies to the corresponding viral proteins of LCDV, no colinearity was detected when the coding strategies of the CIV and LCDV-1 were compared to each other. An intriguing result was the detection of a viral peptide of 53 amino acid residues (ORF 160L) showing high homology (identity/similarity: 60.0%/30.0%) to sillucin, an antibiotic peptide encoded by Rhizomucor pusillus. Iridovirus homologs of cellular genes possess particular implications for the molecular evolution of large DNA viruses.
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The Complete DNA Sequence of Lymphocystis Disease Virus
Virology, 1997Co-Authors: Christian A. Tidona, Gholamreza DaraiAbstract:Lymphocystis disease virus (LCDV) is the causative agent of lymphocystis disease, which has been reported to occur in over 100 different fish species worldwide. LCDV is a member of the familyIridoviridaeand the type species of the genus Lymphocystivirus. The virions contain a single linear double-stranded DNA molecule, which is circularly permuted, terminally redundant, and heavily methylated at cytosines in CpG sequences. The complete nucleotide sequence of LCDV-1 (flounder isolate) was determined by automated cycle sequencing and primer walking. The genome of LCDV-1 is 102.653 bp in length and contains 195 open reading frames with coding capacities ranging from 40 to 1199 amino acids. Computer-assisted analyses of the deduced amino acid sequences led to the identification of several putative gene products with significant homologies to entries in protein data banks, such as the two major subunits of the viral DNA-dependent RNA polymerase, DNA polymerase, several protein kinases, two subunits of the Ribonucleoside Diphosphate Reductase, DNA methyltransferase, the viral major capsid protein, insulin-like growth factor, and tumor necrosis factor receptor homolog.
Juliana Denekamp - One of the best experts on this subject based on the ideXlab platform.
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the Ribonucleoside Diphosphate Reductase inhibitor e 2 deoxy fluoromethylene cytidine as a cytotoxic radiosensitizer in vitro
Cancer Research, 1999Co-Authors: Philippe Coucke, Laurent A Decosterd, E Cottin, Xiaoguang Chen, Linquan Sun, Sabine Stern, Nicolas Paschoud, Juliana DenekampAbstract:(E)-2′-Deoxy-(fluoromethylene)cytidine (FMdC) is known as an inhibitor of Ribonucleoside Diphosphate Reductase, a key enzyme in the de novo pathway of DNA synthesis. FMdC was tested as a modifier of radiation response in vitro on a human colon carcinoma cell line (WiDr), and the observed radiosensitization was confirmed on two human cervix cancer cell lines (C33-A and SiHa). Using the clonogenic assay, the effect ratio (ER) at a clinically relevant dose level of 2 Gy was 2.10 (50 nm FMdC), 1.70 (30 nm FMdC), and 1.71 (40 nm FMdC) for the three cell lines WiDr, C33-A, and SiHa, respectively. A more detailed analysis of the importance of timing and concentration of FMdC was done on the WiDr cell line alone, yielding an increased ER(2Gy) with increasing concentration and duration of exposure to the drug, ranging from 1.0 (6 h) to 1.8 (72 h) at 30 nm FMdC and from 1.2 (6 h) to 3.5 (24 h) at 300 nm. We investigated the effect of FMdC on the cellular deoxynucleotide triphosphate pool in WiDr cells and demonstrated a marked depletion of dATP and a significant rise of TTP levels. Cell cycle analysis showed early S-phase accumulation induced by FMdC alone, G2-M block induced by irradiation alone, and an increased accumulation of cells in G2-M if both modalities are used. Our data suggest that FMdC is a radiation response modifier in vitro on different cancer cell lines. The observed radiosensitization may in part be explained by alteration of the deoxynucleotide triphosphate pool, which is consistent with the effect of FMdC on Ribonucleoside Diphosphate Reductase.
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The Ribonucleoside Diphosphate Reductase inhibitor (E)-2�-deoxy-(fluoromethylene)cytidine as a cytotoxic radiosensitizer in vitro
1999Co-Authors: Laurent A Decosterd, E Cottin, Xiaoguang Chen, Linquan Sun, Sabine Stern, Nicolas Paschoud, Juliana DenekampAbstract:(E)-2*-Deoxy-(fluoromethylene)cytidine (FMdC) is known as an inhib-itor of Ribonucleoside Diphosphate Reductase, a key enzyme in the de novo pathway of DNA synthesis. FMdC was tested as a modifier of radiation response in vitro on a human colon carcinoma cell line (WiDr), and the observed radiosensitization was confirmed on two human cervix cancer cell lines (C33-A and SiHa). Using the clonogenic assay, the effect ratio (ER) at a clinically relevant dose level of 2 Gy was 2.10 (50 nM FMdC), 1.70 (30 nM FMdC), and 1.71 (40 nM FMdC) for the three cell lines WiDr, C33-A, and SiHa, respectively. A more detailed analysis of the importance of timing and concentration of FMdC was done on the WiDr cell line alone, yielding an increased ER(2Gy) with increasing concentration and duration of exposure to the drug, ranging from 1.0 (6 h) to 1.8 (72 h) at 30 nM FMdC and from 1.2 (6 h) to 3.5 (24 h) at 300 nM. We investigated the effect of FMdC on the cellular deoxynucleotide triphosphate pool in WiDr cells and demonstrated a marked depletion of dATP and a significant rise of TTP levels. Cell cycle analysis showed early S-phase accumulation induced by FMdC alone, G2-M block induced by irradiation alone, and an increased accumulation of cells in G2-M if both modalities are used. Our data suggest that FMdC is a radiation response modifier in vitro on different cancer cell lines. The observed radiosensitization may in part be explained by alteration of the deoxynucleotide triphosphate pool, which is consistent with the effect of FMdC on Ribonucleoside Diphosphate reduc-tase
Alfonso Jimenezsanchez - One of the best experts on this subject based on the ideXlab platform.
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Ribonucleoside Diphosphate Reductase is a component of the replication hyperstructure in escherichia coli
Molecular Microbiology, 2002Co-Authors: Elena C Guzman, Jose Luis Caballero, Alfonso JimenezsanchezAbstract:Summary Although the nrdA101 allele codes for a ribonucleo- side Diphosphate (rNDP) Reductase that is essentially destroyed in less than 2 min at 42∞C, and chemical inhibition of the enzyme by hydroxyurea stops DNA synthesis at once, we found that incubation at 42∞C of an Escherichia coli strain containing this allele allows DNA replication for about 40 min. This sug- gests that mutant rNDP Reductase is protected from thermal inactivation by some hyperstructure. If, to- gether with the temperature upshift, RNA or protein synthesis is inhibited, the thermostability time of the mutant rNDP Reductase becomes at least as long as the replication time and residual DNA synthesis becomes a run-out replication producing fully repli- cated chromosomes. This suggests that cessation of replication in the nrdA101 mutant strain is not the result of inactivation of its gene product but of the activity of a protein reflecting the presence of a par- tially altered enzyme. The absence of Tus protein, which specifically stops the replication complex by inhibiting replicative helicase activity, allows forks to replicate for a longer time at the restrictive tempera- ture in the nrdA101 mutant strain. We therefore propose that rNDP Reductase is a component of the replication complex, and that this association with other proteins protects the protein coded by allele nrdA101 from thermal inactivation.
