Combination with low-dose gemcitabine and hTERT-promoter-dependent conditionally replicative adenovirus enhances cytotoxicity through their crosstalk mechanisms in pancreatic cancer

Manabu Onimaru; Kenoki Ohuchida; Eishi Nagai; Kazuhiro Mizumoto; Takuya Egami; Lin Cui; Norihiro Sato; Junji Uchino; Koichi Takayama; Makoto Hashizume; Masao Tanaka

doi:10.1016/j.canlet.2010.01.034

Combination with low-dose gemcitabine and hTERT-promoter-dependent conditionally replicative adenovirus enhances cytotoxicity through their crosstalk mechanisms in pancreatic cancer

Manabu Onimaru, Kenoki Ohuchida, Eishi Nagai, Kazuhiro Mizumoto, Takuya Egami, Lin Cui, Norihiro Sato, Junji Uchino, Koichi Takayama, Makoto Hashizume, Masao Tanaka

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Abstract

To overcome the limited clinical efficacy of conditionally replicative adenoviruses (CRAds), we investigated the effects of combination therapy with gemcitabine (GEM) and the hTERT-promoter-dependent CRAd (hTERT-CRAd), Ad5/3hTERTE1. This combination therapy exhibited enhanced cytotoxic effects on pancreatic cancer both in vitro and in vivo. Furthermore, we revealed that this enhancement effect was due to the multiple bidirectional interactions between hTERT-CRAd and GEM. The GEM-sensitizing effect of E1 expression derived from hTERT-CRAd, and the enhancement effect by GEM on hTERT promoter activity which led to the increase of adenovirus E1 and viral infectivity. This combination therapy may be a promising therapeutic approach for pancreatic cancer.

Original language	English
Pages (from-to)	178-186
Number of pages	9
Journal	Cancer Letters
Volume	294
Issue number	2
DOIs	https://doi.org/10.1016/j.canlet.2010.01.034
Publication status	Published - Aug 2010

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Onimaru, M., Ohuchida, K., Nagai, E., Mizumoto, K., Egami, T., Cui, L., Sato, N., Uchino, J., Takayama, K., Hashizume, M., & Tanaka, M. (2010). Combination with low-dose gemcitabine and hTERT-promoter-dependent conditionally replicative adenovirus enhances cytotoxicity through their crosstalk mechanisms in pancreatic cancer. Cancer Letters, 294(2), 178-186. https://doi.org/10.1016/j.canlet.2010.01.034

Onimaru, M, Ohuchida, K, Nagai, E, Mizumoto, K, Egami, T, Cui, L, Sato, N, Uchino, J, Takayama, K, Hashizume, M & Tanaka, M 2010, 'Combination with low-dose gemcitabine and hTERT-promoter-dependent conditionally replicative adenovirus enhances cytotoxicity through their crosstalk mechanisms in pancreatic cancer', Cancer Letters, vol. 294, no. 2, pp. 178-186. https://doi.org/10.1016/j.canlet.2010.01.034

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title = "Combination with low-dose gemcitabine and hTERT-promoter-dependent conditionally replicative adenovirus enhances cytotoxicity through their crosstalk mechanisms in pancreatic cancer",

abstract = "To overcome the limited clinical efficacy of conditionally replicative adenoviruses (CRAds), we investigated the effects of combination therapy with gemcitabine (GEM) and the hTERT-promoter-dependent CRAd (hTERT-CRAd), Ad5/3hTERTE1. This combination therapy exhibited enhanced cytotoxic effects on pancreatic cancer both in vitro and in vivo. Furthermore, we revealed that this enhancement effect was due to the multiple bidirectional interactions between hTERT-CRAd and GEM. The GEM-sensitizing effect of E1 expression derived from hTERT-CRAd, and the enhancement effect by GEM on hTERT promoter activity which led to the increase of adenovirus E1 and viral infectivity. This combination therapy may be a promising therapeutic approach for pancreatic cancer.",

author = "Manabu Onimaru and Kenoki Ohuchida and Eishi Nagai and Kazuhiro Mizumoto and Takuya Egami and Lin Cui and Norihiro Sato and Junji Uchino and Koichi Takayama and Makoto Hashizume and Masao Tanaka",

note = "Funding Information: Supported by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. ",

year = "2010",

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doi = "10.1016/j.canlet.2010.01.034",

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T1 - Combination with low-dose gemcitabine and hTERT-promoter-dependent conditionally replicative adenovirus enhances cytotoxicity through their crosstalk mechanisms in pancreatic cancer

AU - Onimaru, Manabu

AU - Ohuchida, Kenoki

AU - Nagai, Eishi

AU - Mizumoto, Kazuhiro

AU - Egami, Takuya

AU - Cui, Lin

AU - Sato, Norihiro

AU - Uchino, Junji

AU - Takayama, Koichi

AU - Hashizume, Makoto

AU - Tanaka, Masao

N1 - Funding Information: Supported by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

PY - 2010/8

Y1 - 2010/8

N2 - To overcome the limited clinical efficacy of conditionally replicative adenoviruses (CRAds), we investigated the effects of combination therapy with gemcitabine (GEM) and the hTERT-promoter-dependent CRAd (hTERT-CRAd), Ad5/3hTERTE1. This combination therapy exhibited enhanced cytotoxic effects on pancreatic cancer both in vitro and in vivo. Furthermore, we revealed that this enhancement effect was due to the multiple bidirectional interactions between hTERT-CRAd and GEM. The GEM-sensitizing effect of E1 expression derived from hTERT-CRAd, and the enhancement effect by GEM on hTERT promoter activity which led to the increase of adenovirus E1 and viral infectivity. This combination therapy may be a promising therapeutic approach for pancreatic cancer.

AB - To overcome the limited clinical efficacy of conditionally replicative adenoviruses (CRAds), we investigated the effects of combination therapy with gemcitabine (GEM) and the hTERT-promoter-dependent CRAd (hTERT-CRAd), Ad5/3hTERTE1. This combination therapy exhibited enhanced cytotoxic effects on pancreatic cancer both in vitro and in vivo. Furthermore, we revealed that this enhancement effect was due to the multiple bidirectional interactions between hTERT-CRAd and GEM. The GEM-sensitizing effect of E1 expression derived from hTERT-CRAd, and the enhancement effect by GEM on hTERT promoter activity which led to the increase of adenovirus E1 and viral infectivity. This combination therapy may be a promising therapeutic approach for pancreatic cancer.

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JO - Cancer Letters

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Combination with low-dose gemcitabine and hTERT-promoter-dependent conditionally replicative adenovirus enhances cytotoxicity through their crosstalk mechanisms in pancreatic cancer

Abstract

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UN SDGs

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