A phase II study employing combination regimens containing KRN8602 in drug-resistant acute myeloid leukemia and acute lymphoblastic leukemia

Kishimoto, Yuji; Sampi, K; Kuraishi, Yasushi; Takemoto, Y; Okabe, Keisuke; Tamura, Kazuki; Mizoguchi, H; Saito, Hidehiko; Masaoka, T; Ogawa, M

doi:10.1097/00001813-199903000-00003

Cited by 2 publications

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“…Anticancer drug resistance is a major obstacle in the treatment of leukemia, therefore many trials evaluating leukemia treatment have been conducted (22)(23)(24). In this study, combined treatment with indomethacin was shown to potentiate a chemotherapy-induced apoptosis in drug-resistant AML-2/ IDAC cells.…”

Section: Discussionmentioning

confidence: 86%

Alleviation of the drug-resistant phenotype in idarubicin and cytosine arabinoside double-resistant acute myeloid leukemia cells by indomethacin

Song

Kim²,

Kim³

et al. 2008

Int J Oncol

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Chemoresistance to anticancer drugs is a major issue in the successful treatment of acute myeloid leukemia (AML). In this study, we developed an AML cell line (AML-2/IDAC) that is resistant to treatment with a combination of idarubicin and cytosine arabinoside (Id/AraC) by chronic exposure for more than 3 months. We then investigated the ability of indomethacin to alleviate the chemoresistance of AML-2/IDAC cells. Treatment with indomethacin alone induced growth arrest, but not the death of AML-2/IDAC cells. However, when AML-2/IDAC cells were treated with combinations of indomethacin and Id/AraC, the cell death and apoptosis rate of AML-2/IDAC cells were significantly increased in a dose-and time-dependent manner. The combined treatment with indomethacin and Id/AraC caused the collapse of the mitochondrial membrane potential and was also demonstrated to enhance the activities of caspase-3 and-8 in AML-2/IDAC cells. Furthermore, indomethacin down-regulated expression of the ABCA3 and MRP1 genes, which were over-expressed in AML-2/IDAC cells. Taken together, the results of this study suggest that indomethacin can be used to increase the therapeutic potential against drug-resistant AML when combined with anti-leukemic drugs.

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Section: Discussionmentioning

confidence: 86%

Alleviation of the drug-resistant phenotype in idarubicin and cytosine arabinoside double-resistant acute myeloid leukemia cells by indomethacin

Song

Kim²,

Kim³

et al. 2008

Int J Oncol

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Mizumatsu

Matsumoto

Ono

et al. 2000

Journal of Neuro-Oncology

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We examined whether the intrathecal MX2 chemotherapy for treating dissemination of malignant glioma would be a feasible therapy. In the toxicity study, physiological and histological neurotoxicity was not observed in the rats treated with less than 100 microg/kg of MX2 administered intracisternally. But physiological side effects were observed in the treatment group of more than 200 microg/kg and histological brain toxicity was in the treatment group of more than 1000 microg/kg. Dissemination models were induced in rats by intracisternal inoculation of C6 glioma cells. The median survival times of the rats treated with 100 microg/kg of intrathecal MX2 on day 1, 3, or 7 after tumor inoculation were prolonged by 52.4% (p = 0.0006), 31.5% (p = 0.0007), and 7.1% (p = 0.0180), respectively, compared to that of untreated control animals. Intrathecal MX2 treatment also cured 33.6% of rats in the treatment group. These findings suggested that there was a possibility that intrathecal MX2 would be a safe and effective method for treating dissemination of malignant glioma.

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A phase II study employing combination regimens containing KRN8602 in drug-resistant acute myeloid leukemia and acute lymphoblastic leukemia

Cited by 2 publications

References 0 publications

Alleviation of the drug-resistant phenotype in idarubicin and cytosine arabinoside double-resistant acute myeloid leukemia cells by indomethacin

Alleviation of the drug-resistant phenotype in idarubicin and cytosine arabinoside double-resistant acute myeloid leukemia cells by indomethacin

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