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Adam Mccluskey - One of the best experts on this subject based on the ideXlab platform.

  • Serine/threonine protein phosphatase Inhibition enhances the effect of thymidylate synthase Inhibition
    Cancer Chemotherapy and Pharmacology, 2004
    Co-Authors: Jennette A. Sakoff, Ian J. Howitt, Stephen P Ackland, Adam Mccluskey
    Abstract:

    Purpose The serine/threonine protein phosphatases 1 (PP1) and 2A (PP2A) are key enzymes in regulating entry into the cell cycle, mitosis and apoptosis. Inhibition of PP1 and PP2A is associated with enhanced S-phase entry culminating in G_2/M arrest and apoptotic cell death. Thymidylate synthase (TS) is a key regulatory enzyme in DNA Synthesis, Inhibition of which is often a first-line treatment for colorectal carcinoma. In this study the effect of combining PP Inhibition with TS Inhibition in two colorectal cell lines was examined. Methods Cantharidin and nolatrexed were used to inhibit PP and TS activity, respectively. The MTT cytotoxicity assay and cell cycle analysis were performed following single-drug treatment of HT29 and HCT116 colorectal cell lines. The median effect method was used to determine a combination index (CI), where drug antagonism was indicated by a CI>1.1, additivity by a CI between 0.9 and 1.1, and synergism by a CI

  • Serine/threonine protein phosphatase Inhibition enhances the effect of thymidylate synthase Inhibition
    Cancer chemotherapy and pharmacology, 2003
    Co-Authors: Jennette A. Sakoff, Ian J. Howitt, Stephen P Ackland, Adam Mccluskey
    Abstract:

    Purpose The serine/threonine protein phosphatases 1 (PP1) and 2A (PP2A) are key enzymes in regulating entry into the cell cycle, mitosis and apoptosis. Inhibition of PP1 and PP2A is associated with enhanced S-phase entry culminating in G2/M arrest and apoptotic cell death. Thymidylate synthase (TS) is a key regulatory enzyme in DNA Synthesis, Inhibition of which is often a first-line treatment for colorectal carcinoma. In this study the effect of combining PP Inhibition with TS Inhibition in two colorectal cell lines was examined.

Jennette A. Sakoff - One of the best experts on this subject based on the ideXlab platform.

  • Serine/threonine protein phosphatase Inhibition enhances the effect of thymidylate synthase Inhibition
    Cancer Chemotherapy and Pharmacology, 2004
    Co-Authors: Jennette A. Sakoff, Ian J. Howitt, Stephen P Ackland, Adam Mccluskey
    Abstract:

    Purpose The serine/threonine protein phosphatases 1 (PP1) and 2A (PP2A) are key enzymes in regulating entry into the cell cycle, mitosis and apoptosis. Inhibition of PP1 and PP2A is associated with enhanced S-phase entry culminating in G_2/M arrest and apoptotic cell death. Thymidylate synthase (TS) is a key regulatory enzyme in DNA Synthesis, Inhibition of which is often a first-line treatment for colorectal carcinoma. In this study the effect of combining PP Inhibition with TS Inhibition in two colorectal cell lines was examined. Methods Cantharidin and nolatrexed were used to inhibit PP and TS activity, respectively. The MTT cytotoxicity assay and cell cycle analysis were performed following single-drug treatment of HT29 and HCT116 colorectal cell lines. The median effect method was used to determine a combination index (CI), where drug antagonism was indicated by a CI>1.1, additivity by a CI between 0.9 and 1.1, and synergism by a CI

  • Serine/threonine protein phosphatase Inhibition enhances the effect of thymidylate synthase Inhibition
    Cancer chemotherapy and pharmacology, 2003
    Co-Authors: Jennette A. Sakoff, Ian J. Howitt, Stephen P Ackland, Adam Mccluskey
    Abstract:

    Purpose The serine/threonine protein phosphatases 1 (PP1) and 2A (PP2A) are key enzymes in regulating entry into the cell cycle, mitosis and apoptosis. Inhibition of PP1 and PP2A is associated with enhanced S-phase entry culminating in G2/M arrest and apoptotic cell death. Thymidylate synthase (TS) is a key regulatory enzyme in DNA Synthesis, Inhibition of which is often a first-line treatment for colorectal carcinoma. In this study the effect of combining PP Inhibition with TS Inhibition in two colorectal cell lines was examined.

Ian J. Howitt - One of the best experts on this subject based on the ideXlab platform.

  • Serine/threonine protein phosphatase Inhibition enhances the effect of thymidylate synthase Inhibition
    Cancer Chemotherapy and Pharmacology, 2004
    Co-Authors: Jennette A. Sakoff, Ian J. Howitt, Stephen P Ackland, Adam Mccluskey
    Abstract:

    Purpose The serine/threonine protein phosphatases 1 (PP1) and 2A (PP2A) are key enzymes in regulating entry into the cell cycle, mitosis and apoptosis. Inhibition of PP1 and PP2A is associated with enhanced S-phase entry culminating in G_2/M arrest and apoptotic cell death. Thymidylate synthase (TS) is a key regulatory enzyme in DNA Synthesis, Inhibition of which is often a first-line treatment for colorectal carcinoma. In this study the effect of combining PP Inhibition with TS Inhibition in two colorectal cell lines was examined. Methods Cantharidin and nolatrexed were used to inhibit PP and TS activity, respectively. The MTT cytotoxicity assay and cell cycle analysis were performed following single-drug treatment of HT29 and HCT116 colorectal cell lines. The median effect method was used to determine a combination index (CI), where drug antagonism was indicated by a CI>1.1, additivity by a CI between 0.9 and 1.1, and synergism by a CI

  • Serine/threonine protein phosphatase Inhibition enhances the effect of thymidylate synthase Inhibition
    Cancer chemotherapy and pharmacology, 2003
    Co-Authors: Jennette A. Sakoff, Ian J. Howitt, Stephen P Ackland, Adam Mccluskey
    Abstract:

    Purpose The serine/threonine protein phosphatases 1 (PP1) and 2A (PP2A) are key enzymes in regulating entry into the cell cycle, mitosis and apoptosis. Inhibition of PP1 and PP2A is associated with enhanced S-phase entry culminating in G2/M arrest and apoptotic cell death. Thymidylate synthase (TS) is a key regulatory enzyme in DNA Synthesis, Inhibition of which is often a first-line treatment for colorectal carcinoma. In this study the effect of combining PP Inhibition with TS Inhibition in two colorectal cell lines was examined.

Stephen P Ackland - One of the best experts on this subject based on the ideXlab platform.

  • Serine/threonine protein phosphatase Inhibition enhances the effect of thymidylate synthase Inhibition
    Cancer Chemotherapy and Pharmacology, 2004
    Co-Authors: Jennette A. Sakoff, Ian J. Howitt, Stephen P Ackland, Adam Mccluskey
    Abstract:

    Purpose The serine/threonine protein phosphatases 1 (PP1) and 2A (PP2A) are key enzymes in regulating entry into the cell cycle, mitosis and apoptosis. Inhibition of PP1 and PP2A is associated with enhanced S-phase entry culminating in G_2/M arrest and apoptotic cell death. Thymidylate synthase (TS) is a key regulatory enzyme in DNA Synthesis, Inhibition of which is often a first-line treatment for colorectal carcinoma. In this study the effect of combining PP Inhibition with TS Inhibition in two colorectal cell lines was examined. Methods Cantharidin and nolatrexed were used to inhibit PP and TS activity, respectively. The MTT cytotoxicity assay and cell cycle analysis were performed following single-drug treatment of HT29 and HCT116 colorectal cell lines. The median effect method was used to determine a combination index (CI), where drug antagonism was indicated by a CI>1.1, additivity by a CI between 0.9 and 1.1, and synergism by a CI

  • Serine/threonine protein phosphatase Inhibition enhances the effect of thymidylate synthase Inhibition
    Cancer chemotherapy and pharmacology, 2003
    Co-Authors: Jennette A. Sakoff, Ian J. Howitt, Stephen P Ackland, Adam Mccluskey
    Abstract:

    Purpose The serine/threonine protein phosphatases 1 (PP1) and 2A (PP2A) are key enzymes in regulating entry into the cell cycle, mitosis and apoptosis. Inhibition of PP1 and PP2A is associated with enhanced S-phase entry culminating in G2/M arrest and apoptotic cell death. Thymidylate synthase (TS) is a key regulatory enzyme in DNA Synthesis, Inhibition of which is often a first-line treatment for colorectal carcinoma. In this study the effect of combining PP Inhibition with TS Inhibition in two colorectal cell lines was examined.

Donna S. Shewach - One of the best experts on this subject based on the ideXlab platform.

  • The role of DNA Synthesis Inhibition in the cytotoxicity of 2',2'-difluoro-2'-deoxycytidine.
    Cancer Chemotherapy and Pharmacology, 2003
    Co-Authors: Leo J. Ostruszka, Donna S. Shewach
    Abstract:

    Purpose Cytotoxicity from the anticancer drug 2′,2′-difluoro-2′-deoxycytidine (dFdCyd) has been correlated with its incorporation into DNA. However, cytotoxicity may also result from Inhibition of DNA Synthesis, due to either (1) dFdCyd diphosphate-mediated Inhibition of ribonucleotide reductase, or (2) direct Inhibition of DNA polymerases by the 5′-triphosphate of dFdCyd (dFdCTP). To elucidate the role of DNA Synthesis Inhibition in the cytotoxicity of dFdCyd, we compared dFdCyd to hydroxyurea (HU), a ribonucleotide reductase inhibitor, and aphidicolin, an inhibitor of DNA polymerases, in the U251 and D54 human glioblastoma cell lines.

  • Hydroxyurea significantly enhances tumor growth delay in vivo with herpes simplex virus thymidine kinase/ganciclovir gene therapy.
    Gene therapy, 2002
    Co-Authors: Paul D. Boucher, Leo J. Ostruszka, Patrick J. Murphy, Donna S. Shewach
    Abstract:

    We have previously demonstrated with several cell lines in vitro that hydroxyurea (HU) synergistically enhances ganciclovir (GCV)-mediated cytotoxicity in bystander cells. In this study, we evaluated the role of DNA Synthesis Inhibition on enhanced bystander killing and assessed whether addition of HU would improve the efficacy of the HSV-TK/GCV system in vivo. Compared with GCV treatment alone, addition of HU resulted in increased DNA Synthesis Inhibition and delayed progression through S phase following removal of drug. In a xenograft tumor model, 1:10 and 1:1 mixtures of HSVtk- and LacZ-expressing SW620 cells were injected s.c. in the flanks of nude mice and treated i.p. (100 mg/kg GCV, 1500 mg/kg HU) daily for 5 days. Tumors from mice treated with GCV alone grew rapidly and increased to 10 times their initial size in 15.7 +/- 1.8 and 16.0 +/- 0.9 days for 1:10 and 1:1 mixtures, respectively. However, when both GCV and HU were administered in combination, a single complete tumor regression was observed in both the 1:10 and 1:1 groups. In the remaining mice treated with GCV/HU, it took 23.2 +/- 2.1 (1:10) and 26.4 +/- 3.8 days (1:1) to obtain a similar 10-fold increase in tumor size.