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Combinatory cytotoxic effects produced by E1B-55kDa-deleted adenoviruses and chemotherapeutic agents are dependent on the agents in esophageal carcinoma.

Ma G, Kawamura K, Li Q, Okamoto S, Suzuki N, Kobayashi H, Liang M, Tada Y, Tatsumi K, Hiroshima K, Shimada H, Tagawa M - Cancer Gene Ther. (2010)

Bottom Line: We also confirmed the antitumor effects by the combination of Ad-delE1B55 with 5-FU in vivo.Cisplatin, however, did not achieve the combinatory effects in most of the cells tested.These data indicate that the Ad-delE1B55 produce combinatory antitumor effects with a chemotherapeutic agent irrespective of the administration schedule, but the effects depend on an agent in esophageal carcinoma.

View Article: PubMed Central - PubMed

Affiliation: Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chiba, Japan.

ABSTRACT
We examined possible combinatory antitumor effects of replication-competent type 5 adenoviruses (Ad) lacking E1B-55kDa molecules (Ad-delE1B55) and chemotherapeutic agents in nine human esophageal carcinoma cells. Ad-delE1B55 produced cytotoxic effects on all the carcinoma cells and the cytotoxicity is not directly linked with the p53 status of the tumors or with the infectivity to respective tumors. A combinatory treatment with Ad-delE1B55 and an anticancer agent, 5-fluorouracil (5-FU), mitomycin C or etoposide, produced greater cytotoxic effects than that with either the Ad or the agent. Administration of 5-FU could minimally inhibit the viral replication and a simultaneous treatment with the Ad and 5-FU achieved better cytotoxicity than sequential treatments. We also confirmed the antitumor effects by the combination of Ad-delE1B55 with 5-FU in vivo. Cisplatin, however, did not achieve the combinatory effects in most of the cells tested. These data indicate that the Ad-delE1B55 produce combinatory antitumor effects with a chemotherapeutic agent irrespective of the administration schedule, but the effects depend on an agent in esophageal carcinoma.

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(a) Cytotoxic activities of Ad-delE1B55 and Ad-LacZ as a control to esophageal carcinoma cells. s.e. bars (n=3) are also shown. (b) Cytotoxic activities of Ad-delE1B55 and Ad-LacZ as a control to HFF and IF cells. Asterisks show P<0.05 (HFF/Ad-delE1B55 vs IF/Ad-delE1B55) (n=3).
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fig2: (a) Cytotoxic activities of Ad-delE1B55 and Ad-LacZ as a control to esophageal carcinoma cells. s.e. bars (n=3) are also shown. (b) Cytotoxic activities of Ad-delE1B55 and Ad-LacZ as a control to HFF and IF cells. Asterisks show P<0.05 (HFF/Ad-delE1B55 vs IF/Ad-delE1B55) (n=3).

Mentions: We examined cytotoxic activity of Ad-delE1B55 in nine kinds of squamous esophageal carcinoma cells (Figure 2a) and found that all the cells were susceptible to Ad-delE1B55. T.Tn cells were exceptionally sensitive to Ad-LacZ at a high MOI, but others were insensitive to the control. We then examined the correlation between the Ad-delE1B55-mediated cytotoxicity and the Ad infectivity, which was evaluated with Ad-GFP (Table 1). We used two indicators, mean GFP fluorescence intensity and percentage of GFP-positive cells, both of which showed Ad infectivity, although the former indicator was also influenced by a cytomegalovirus promoter-mediated transcriptional activity in the cells. We calculated IC50 values of Ad-delE1B55 to respective cells to represent the susceptibility (Table 1) and found that the IC50 values did not correlate with the mean fluorescence intensity (P=0.44) or percentages of the positive cells (P=0.38), suggesting that the Ad-delE1B55 cytotoxicity was not directly linked with the infectivity but depended on the cell type.


Combinatory cytotoxic effects produced by E1B-55kDa-deleted adenoviruses and chemotherapeutic agents are dependent on the agents in esophageal carcinoma.

Ma G, Kawamura K, Li Q, Okamoto S, Suzuki N, Kobayashi H, Liang M, Tada Y, Tatsumi K, Hiroshima K, Shimada H, Tagawa M - Cancer Gene Ther. (2010)

(a) Cytotoxic activities of Ad-delE1B55 and Ad-LacZ as a control to esophageal carcinoma cells. s.e. bars (n=3) are also shown. (b) Cytotoxic activities of Ad-delE1B55 and Ad-LacZ as a control to HFF and IF cells. Asterisks show P<0.05 (HFF/Ad-delE1B55 vs IF/Ad-delE1B55) (n=3).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2963731&req=5

fig2: (a) Cytotoxic activities of Ad-delE1B55 and Ad-LacZ as a control to esophageal carcinoma cells. s.e. bars (n=3) are also shown. (b) Cytotoxic activities of Ad-delE1B55 and Ad-LacZ as a control to HFF and IF cells. Asterisks show P<0.05 (HFF/Ad-delE1B55 vs IF/Ad-delE1B55) (n=3).
Mentions: We examined cytotoxic activity of Ad-delE1B55 in nine kinds of squamous esophageal carcinoma cells (Figure 2a) and found that all the cells were susceptible to Ad-delE1B55. T.Tn cells were exceptionally sensitive to Ad-LacZ at a high MOI, but others were insensitive to the control. We then examined the correlation between the Ad-delE1B55-mediated cytotoxicity and the Ad infectivity, which was evaluated with Ad-GFP (Table 1). We used two indicators, mean GFP fluorescence intensity and percentage of GFP-positive cells, both of which showed Ad infectivity, although the former indicator was also influenced by a cytomegalovirus promoter-mediated transcriptional activity in the cells. We calculated IC50 values of Ad-delE1B55 to respective cells to represent the susceptibility (Table 1) and found that the IC50 values did not correlate with the mean fluorescence intensity (P=0.44) or percentages of the positive cells (P=0.38), suggesting that the Ad-delE1B55 cytotoxicity was not directly linked with the infectivity but depended on the cell type.

Bottom Line: We also confirmed the antitumor effects by the combination of Ad-delE1B55 with 5-FU in vivo.Cisplatin, however, did not achieve the combinatory effects in most of the cells tested.These data indicate that the Ad-delE1B55 produce combinatory antitumor effects with a chemotherapeutic agent irrespective of the administration schedule, but the effects depend on an agent in esophageal carcinoma.

View Article: PubMed Central - PubMed

Affiliation: Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chiba, Japan.

ABSTRACT
We examined possible combinatory antitumor effects of replication-competent type 5 adenoviruses (Ad) lacking E1B-55kDa molecules (Ad-delE1B55) and chemotherapeutic agents in nine human esophageal carcinoma cells. Ad-delE1B55 produced cytotoxic effects on all the carcinoma cells and the cytotoxicity is not directly linked with the p53 status of the tumors or with the infectivity to respective tumors. A combinatory treatment with Ad-delE1B55 and an anticancer agent, 5-fluorouracil (5-FU), mitomycin C or etoposide, produced greater cytotoxic effects than that with either the Ad or the agent. Administration of 5-FU could minimally inhibit the viral replication and a simultaneous treatment with the Ad and 5-FU achieved better cytotoxicity than sequential treatments. We also confirmed the antitumor effects by the combination of Ad-delE1B55 with 5-FU in vivo. Cisplatin, however, did not achieve the combinatory effects in most of the cells tested. These data indicate that the Ad-delE1B55 produce combinatory antitumor effects with a chemotherapeutic agent irrespective of the administration schedule, but the effects depend on an agent in esophageal carcinoma.

Show MeSH
Related in: MedlinePlus