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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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Related in: MedlinePlus

Detection of Ad-delE1B55 DNA and the viral replication in tumor cells. (a) Diagram of primer A and B sets to amplify the outside and inside of the E1B55-kDa-encoding region. An expected size of the PCR product with primer A sets is 2412 bp for Ad-WT and 1585 bp for Ad-delE1B55, and that with primer B sets is 569 bp for Ad-WT and none for Ad-delE1B55. (b) Sequential increase of PCR products. DNA was extracted from the same volume of culture supernatants from Ad-delE1B55-infected TE-1 and YES-4 cells on the indicated day. (c) Deletion of the E1B-55kDa region in DNA extracted from the infected cells. Ad-WT DNA was used as a control.
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fig1: Detection of Ad-delE1B55 DNA and the viral replication in tumor cells. (a) Diagram of primer A and B sets to amplify the outside and inside of the E1B55-kDa-encoding region. An expected size of the PCR product with primer A sets is 2412 bp for Ad-WT and 1585 bp for Ad-delE1B55, and that with primer B sets is 569 bp for Ad-WT and none for Ad-delE1B55. (b) Sequential increase of PCR products. DNA was extracted from the same volume of culture supernatants from Ad-delE1B55-infected TE-1 and YES-4 cells on the indicated day. (c) Deletion of the E1B-55kDa region in DNA extracted from the infected cells. Ad-WT DNA was used as a control.

Mentions: We examined release of Ad-delE1B55 from infected TE-1 and YES-4 cells with PCR using primer sets that were designed to cover the whole E1B region (Figure 1a). The expected E1B-55kDa-deleted DNA was amplified from the culture supernatants and the amount increased after the infection (Figure 1b). Accompanied amplification of GAPDH bands showed increased cell destruction by Ad-delE1B55. We further confirmed the deleted E1B55kDa region with two kinds of primer sets that distinguished the deletion and Ad-WT DNA (Figure 1c). These data showed that Ad-delE1B55 destroyed the infected cells, and the progenies were released without producing Ad-WT.


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)

Detection of Ad-delE1B55 DNA and the viral replication in tumor cells. (a) Diagram of primer A and B sets to amplify the outside and inside of the E1B55-kDa-encoding region. An expected size of the PCR product with primer A sets is 2412 bp for Ad-WT and 1585 bp for Ad-delE1B55, and that with primer B sets is 569 bp for Ad-WT and none for Ad-delE1B55. (b) Sequential increase of PCR products. DNA was extracted from the same volume of culture supernatants from Ad-delE1B55-infected TE-1 and YES-4 cells on the indicated day. (c) Deletion of the E1B-55kDa region in DNA extracted from the infected cells. Ad-WT DNA was used as a control.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Detection of Ad-delE1B55 DNA and the viral replication in tumor cells. (a) Diagram of primer A and B sets to amplify the outside and inside of the E1B55-kDa-encoding region. An expected size of the PCR product with primer A sets is 2412 bp for Ad-WT and 1585 bp for Ad-delE1B55, and that with primer B sets is 569 bp for Ad-WT and none for Ad-delE1B55. (b) Sequential increase of PCR products. DNA was extracted from the same volume of culture supernatants from Ad-delE1B55-infected TE-1 and YES-4 cells on the indicated day. (c) Deletion of the E1B-55kDa region in DNA extracted from the infected cells. Ad-WT DNA was used as a control.
Mentions: We examined release of Ad-delE1B55 from infected TE-1 and YES-4 cells with PCR using primer sets that were designed to cover the whole E1B region (Figure 1a). The expected E1B-55kDa-deleted DNA was amplified from the culture supernatants and the amount increased after the infection (Figure 1b). Accompanied amplification of GAPDH bands showed increased cell destruction by Ad-delE1B55. We further confirmed the deleted E1B55kDa region with two kinds of primer sets that distinguished the deletion and Ad-WT DNA (Figure 1c). These data showed that Ad-delE1B55 destroyed the infected cells, and the progenies were released without producing Ad-WT.

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