Oncolytic Viral Therapy for Human Pancreatic Cancer Cells by Reovirus

Purpose: Pancreatic cancer has a poor prognosis and few effective therapies are available. The oncolytic effect of reovirus has been observed in cancer cells with an activated Ras signaling pathway, and pancreatic cancer may be a candidate target for reovirus because K-ras mutation is frequently fou...

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Veröffentlicht in:Clinical cancer research 2003-03, Vol.9 (3), p.1218-1223
Hauptverfasser: ETOH, Tsuyoshi, HIMENO, Yoshihisa, MATSUMOTO, Toshifumi, ARAMAKI, Masanori, KAWANO, Katsunori, NISHIZONO, Akira, KITANO, Seigo
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container_end_page 1223
container_issue 3
container_start_page 1218
container_title Clinical cancer research
container_volume 9
creator ETOH, Tsuyoshi
HIMENO, Yoshihisa
MATSUMOTO, Toshifumi
ARAMAKI, Masanori
KAWANO, Katsunori
NISHIZONO, Akira
KITANO, Seigo
description Purpose: Pancreatic cancer has a poor prognosis and few effective therapies are available. The oncolytic effect of reovirus has been observed in cancer cells with an activated Ras signaling pathway, and pancreatic cancer may be a candidate target for reovirus because K-ras mutation is frequently found in pancreatic cancer. Experimental Design: In this study, we examined the feasibility of using reovirus (serotype 3) as an antihuman pancreatic cancer agent. Results: Reovirus was able to infect five human pancreatic cancer cell lines (Panc1, MIApaca-2, PK1, PK9, and BxPC3) in vitro . We also confirmed that the Ras activity in these cancer cell lines was elevated compared with that in the normal cell line and that susceptibility to reovirus was associated with the Ras activity of these cells. In a unilateral murine xenograft model using Panc1 and BxPC3 cell lines, each tumor growth was suppressed by intratumoral injection of reovirus. Furthermore, local injection of reovirus also had systemic antitumor effects in a bilateral xenograft model using Panc1 cell line. Immunohistochemical examination revealed that reovirus replication was observed within the tumor but not in surrounding normal tissue. Conclusions: These results suggest that reovirus can be considered for a novel therapy against pancreatic cancer.
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The oncolytic effect of reovirus has been observed in cancer cells with an activated Ras signaling pathway, and pancreatic cancer may be a candidate target for reovirus because K-ras mutation is frequently found in pancreatic cancer. Experimental Design: In this study, we examined the feasibility of using reovirus (serotype 3) as an antihuman pancreatic cancer agent. Results: Reovirus was able to infect five human pancreatic cancer cell lines (Panc1, MIApaca-2, PK1, PK9, and BxPC3) in vitro . We also confirmed that the Ras activity in these cancer cell lines was elevated compared with that in the normal cell line and that susceptibility to reovirus was associated with the Ras activity of these cells. In a unilateral murine xenograft model using Panc1 and BxPC3 cell lines, each tumor growth was suppressed by intratumoral injection of reovirus. Furthermore, local injection of reovirus also had systemic antitumor effects in a bilateral xenograft model using Panc1 cell line. Immunohistochemical examination revealed that reovirus replication was observed within the tumor but not in surrounding normal tissue. Conclusions: These results suggest that reovirus can be considered for a novel therapy against pancreatic cancer.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>PMID: 12631628</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>3T3 Cells ; Animals ; Biological and medical sciences ; Cell Line ; Genes, ras - genetics ; Humans ; Immunohistochemistry ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Mutation ; Neoplasm Transplantation ; Other treatments ; Pancreatic Neoplasms - pathology ; Pancreatic Neoplasms - therapy ; ras Proteins - metabolism ; Reoviridae - genetics ; Signal Transduction ; Time Factors ; Treatment. 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The oncolytic effect of reovirus has been observed in cancer cells with an activated Ras signaling pathway, and pancreatic cancer may be a candidate target for reovirus because K-ras mutation is frequently found in pancreatic cancer. Experimental Design: In this study, we examined the feasibility of using reovirus (serotype 3) as an antihuman pancreatic cancer agent. Results: Reovirus was able to infect five human pancreatic cancer cell lines (Panc1, MIApaca-2, PK1, PK9, and BxPC3) in vitro . We also confirmed that the Ras activity in these cancer cell lines was elevated compared with that in the normal cell line and that susceptibility to reovirus was associated with the Ras activity of these cells. In a unilateral murine xenograft model using Panc1 and BxPC3 cell lines, each tumor growth was suppressed by intratumoral injection of reovirus. Furthermore, local injection of reovirus also had systemic antitumor effects in a bilateral xenograft model using Panc1 cell line. Immunohistochemical examination revealed that reovirus replication was observed within the tumor but not in surrounding normal tissue. Conclusions: These results suggest that reovirus can be considered for a novel therapy against pancreatic cancer.</description><subject>3T3 Cells</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>Genes, ras - genetics</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mutation</subject><subject>Neoplasm Transplantation</subject><subject>Other treatments</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Pancreatic Neoplasms - therapy</subject><subject>ras Proteins - metabolism</subject><subject>Reoviridae - genetics</subject><subject>Signal Transduction</subject><subject>Time Factors</subject><subject>Treatment. 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The oncolytic effect of reovirus has been observed in cancer cells with an activated Ras signaling pathway, and pancreatic cancer may be a candidate target for reovirus because K-ras mutation is frequently found in pancreatic cancer. Experimental Design: In this study, we examined the feasibility of using reovirus (serotype 3) as an antihuman pancreatic cancer agent. Results: Reovirus was able to infect five human pancreatic cancer cell lines (Panc1, MIApaca-2, PK1, PK9, and BxPC3) in vitro . We also confirmed that the Ras activity in these cancer cell lines was elevated compared with that in the normal cell line and that susceptibility to reovirus was associated with the Ras activity of these cells. In a unilateral murine xenograft model using Panc1 and BxPC3 cell lines, each tumor growth was suppressed by intratumoral injection of reovirus. Furthermore, local injection of reovirus also had systemic antitumor effects in a bilateral xenograft model using Panc1 cell line. Immunohistochemical examination revealed that reovirus replication was observed within the tumor but not in surrounding normal tissue. Conclusions: These results suggest that reovirus can be considered for a novel therapy against pancreatic cancer.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>12631628</pmid><tpages>6</tpages></addata></record>
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source MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection
subjects 3T3 Cells
Animals
Biological and medical sciences
Cell Line
Genes, ras - genetics
Humans
Immunohistochemistry
Medical sciences
Mice
Mice, Inbred BALB C
Mutation
Neoplasm Transplantation
Other treatments
Pancreatic Neoplasms - pathology
Pancreatic Neoplasms - therapy
ras Proteins - metabolism
Reoviridae - genetics
Signal Transduction
Time Factors
Treatment. General aspects
Tumor Cells, Cultured
Tumors
title Oncolytic Viral Therapy for Human Pancreatic Cancer Cells by Reovirus
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