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In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents
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| Zeitschriftentitel: | Blood |
|---|---|
| Personen und Körperschaften: | , , , , , , |
| In: | Blood, 97, 2001, 7, S. 1999-2007 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society of Hematology
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| Schlagwörter: |
| author_facet |
Kano, Yasuhiko Akutsu, Miyuki Tsunoda, Saburo Mano, Hiroyuki Sato, Yuko Honma, Yoshio Furukawa, Yusuke Kano, Yasuhiko Akutsu, Miyuki Tsunoda, Saburo Mano, Hiroyuki Sato, Yuko Honma, Yoshio Furukawa, Yusuke |
|---|---|
| author |
Kano, Yasuhiko Akutsu, Miyuki Tsunoda, Saburo Mano, Hiroyuki Sato, Yuko Honma, Yoshio Furukawa, Yusuke |
| spellingShingle |
Kano, Yasuhiko Akutsu, Miyuki Tsunoda, Saburo Mano, Hiroyuki Sato, Yuko Honma, Yoshio Furukawa, Yusuke Blood In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents Cell Biology Hematology Immunology Biochemistry |
| author_sort |
kano, yasuhiko |
| spelling |
Kano, Yasuhiko Akutsu, Miyuki Tsunoda, Saburo Mano, Hiroyuki Sato, Yuko Honma, Yoshio Furukawa, Yusuke 1528-0020 0006-4971 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood.v97.7.1999 <jats:title>Abstract</jats:title> <jats:p>The BCR/ABL tyrosine kinase has been implicated in the pathogenesis of chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). STI571 is a novel anticancer agent that selectively inhibits the BCR/ABL tyrosine kinase. The cytotoxic effects of STI571 were studied in combination with antileukemic agents against Ph+leukemia cell lines, KU812, K-562, TCC-S, and TCC-Y. The cells were exposed to STI571 and to other agents simultaneously for 5 or 7 days. Cell growth inhibition was determined by MTT assay. The cytotoxic effects in combinations at the inhibitory concentration of 80% level were evaluated by the isobologram. STI571 produced synergistic effects with recombinant and natural α-interferons in 2 of 3 and 3 of 3 cell lines, respectively. STI571 produced additive effects with hydroxyurea, cytarabine, homoharringtonine, doxorubicin, and etoposide in all 4 cell lines. STI571 with 4-hydroperoxy-cyclophosphamide, methotrexate, or vincristine produced additive, antagonistic, and synergistic effects in 3 of 4 cell lines, respectively. These findings suggest that the simultaneous administration of STI571 with other agents except methotrexate would be advantageous for cytotoxic effects against Ph+ leukemias. Among them, the simultaneous administration of STI571 and α-interferons or vincristine would be highly effective against Ph+ leukemias and these combinations would be worthy of clinical trials. In contrast, the simultaneous administration of STI571 with methotrexate would have little therapeutic efficacy. Although there are gaps between in vitro studies and clinical trials, the present findings provide useful information for the establishment of clinical protocols involving STI571.</jats:p> In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents Blood |
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10.1182/blood.v97.7.1999 |
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American Society of Hematology, 2001 |
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| title |
In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents |
| title_unstemmed |
In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents |
| title_full |
In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents |
| title_fullStr |
In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents |
| title_full_unstemmed |
In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents |
| title_short |
In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents |
| title_sort |
in vitro cytotoxic effects of a tyrosine kinase inhibitor sti571 in combination with commonly used antileukemic agents |
| topic |
Cell Biology Hematology Immunology Biochemistry |
| url |
http://dx.doi.org/10.1182/blood.v97.7.1999 |
| publishDate |
2001 |
| physical |
1999-2007 |
| description |
<jats:title>Abstract</jats:title>
<jats:p>The BCR/ABL tyrosine kinase has been implicated in the pathogenesis of chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). STI571 is a novel anticancer agent that selectively inhibits the BCR/ABL tyrosine kinase. The cytotoxic effects of STI571 were studied in combination with antileukemic agents against Ph+leukemia cell lines, KU812, K-562, TCC-S, and TCC-Y. The cells were exposed to STI571 and to other agents simultaneously for 5 or 7 days. Cell growth inhibition was determined by MTT assay. The cytotoxic effects in combinations at the inhibitory concentration of 80% level were evaluated by the isobologram. STI571 produced synergistic effects with recombinant and natural α-interferons in 2 of 3 and 3 of 3 cell lines, respectively. STI571 produced additive effects with hydroxyurea, cytarabine, homoharringtonine, doxorubicin, and etoposide in all 4 cell lines. STI571 with 4-hydroperoxy-cyclophosphamide, methotrexate, or vincristine produced additive, antagonistic, and synergistic effects in 3 of 4 cell lines, respectively. These findings suggest that the simultaneous administration of STI571 with other agents except methotrexate would be advantageous for cytotoxic effects against Ph+ leukemias. Among them, the simultaneous administration of STI571 and α-interferons or vincristine would be highly effective against Ph+ leukemias and these combinations would be worthy of clinical trials. In contrast, the simultaneous administration of STI571 with methotrexate would have little therapeutic efficacy. Although there are gaps between in vitro studies and clinical trials, the present findings provide useful information for the establishment of clinical protocols involving STI571.</jats:p> |
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| author | Kano, Yasuhiko, Akutsu, Miyuki, Tsunoda, Saburo, Mano, Hiroyuki, Sato, Yuko, Honma, Yoshio, Furukawa, Yusuke |
| author_facet | Kano, Yasuhiko, Akutsu, Miyuki, Tsunoda, Saburo, Mano, Hiroyuki, Sato, Yuko, Honma, Yoshio, Furukawa, Yusuke, Kano, Yasuhiko, Akutsu, Miyuki, Tsunoda, Saburo, Mano, Hiroyuki, Sato, Yuko, Honma, Yoshio, Furukawa, Yusuke |
| author_sort | kano, yasuhiko |
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| description | <jats:title>Abstract</jats:title> <jats:p>The BCR/ABL tyrosine kinase has been implicated in the pathogenesis of chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). STI571 is a novel anticancer agent that selectively inhibits the BCR/ABL tyrosine kinase. The cytotoxic effects of STI571 were studied in combination with antileukemic agents against Ph+leukemia cell lines, KU812, K-562, TCC-S, and TCC-Y. The cells were exposed to STI571 and to other agents simultaneously for 5 or 7 days. Cell growth inhibition was determined by MTT assay. The cytotoxic effects in combinations at the inhibitory concentration of 80% level were evaluated by the isobologram. STI571 produced synergistic effects with recombinant and natural α-interferons in 2 of 3 and 3 of 3 cell lines, respectively. STI571 produced additive effects with hydroxyurea, cytarabine, homoharringtonine, doxorubicin, and etoposide in all 4 cell lines. STI571 with 4-hydroperoxy-cyclophosphamide, methotrexate, or vincristine produced additive, antagonistic, and synergistic effects in 3 of 4 cell lines, respectively. These findings suggest that the simultaneous administration of STI571 with other agents except methotrexate would be advantageous for cytotoxic effects against Ph+ leukemias. Among them, the simultaneous administration of STI571 and α-interferons or vincristine would be highly effective against Ph+ leukemias and these combinations would be worthy of clinical trials. In contrast, the simultaneous administration of STI571 with methotrexate would have little therapeutic efficacy. Although there are gaps between in vitro studies and clinical trials, the present findings provide useful information for the establishment of clinical protocols involving STI571.</jats:p> |
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| imprint | American Society of Hematology, 2001 |
| imprint_str_mv | American Society of Hematology, 2001 |
| institution | DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229 |
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| spelling | Kano, Yasuhiko Akutsu, Miyuki Tsunoda, Saburo Mano, Hiroyuki Sato, Yuko Honma, Yoshio Furukawa, Yusuke 1528-0020 0006-4971 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood.v97.7.1999 <jats:title>Abstract</jats:title> <jats:p>The BCR/ABL tyrosine kinase has been implicated in the pathogenesis of chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). STI571 is a novel anticancer agent that selectively inhibits the BCR/ABL tyrosine kinase. The cytotoxic effects of STI571 were studied in combination with antileukemic agents against Ph+leukemia cell lines, KU812, K-562, TCC-S, and TCC-Y. The cells were exposed to STI571 and to other agents simultaneously for 5 or 7 days. Cell growth inhibition was determined by MTT assay. The cytotoxic effects in combinations at the inhibitory concentration of 80% level were evaluated by the isobologram. STI571 produced synergistic effects with recombinant and natural α-interferons in 2 of 3 and 3 of 3 cell lines, respectively. STI571 produced additive effects with hydroxyurea, cytarabine, homoharringtonine, doxorubicin, and etoposide in all 4 cell lines. STI571 with 4-hydroperoxy-cyclophosphamide, methotrexate, or vincristine produced additive, antagonistic, and synergistic effects in 3 of 4 cell lines, respectively. These findings suggest that the simultaneous administration of STI571 with other agents except methotrexate would be advantageous for cytotoxic effects against Ph+ leukemias. Among them, the simultaneous administration of STI571 and α-interferons or vincristine would be highly effective against Ph+ leukemias and these combinations would be worthy of clinical trials. In contrast, the simultaneous administration of STI571 with methotrexate would have little therapeutic efficacy. Although there are gaps between in vitro studies and clinical trials, the present findings provide useful information for the establishment of clinical protocols involving STI571.</jats:p> In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents Blood |
| spellingShingle | Kano, Yasuhiko, Akutsu, Miyuki, Tsunoda, Saburo, Mano, Hiroyuki, Sato, Yuko, Honma, Yoshio, Furukawa, Yusuke, Blood, In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents, Cell Biology, Hematology, Immunology, Biochemistry |
| title | In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents |
| title_full | In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents |
| title_fullStr | In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents |
| title_full_unstemmed | In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents |
| title_short | In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents |
| title_sort | in vitro cytotoxic effects of a tyrosine kinase inhibitor sti571 in combination with commonly used antileukemic agents |
| title_unstemmed | In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents |
| topic | Cell Biology, Hematology, Immunology, Biochemistry |
| url | http://dx.doi.org/10.1182/blood.v97.7.1999 |