Reference - Detail
| RRC ID | 39653 |
|---|---|
| Author | Takeuchi M, Shichinohe T, Senmaru N, Miyamoto M, Fujita H, Takimoto M, Kondo S, Katoh H, Kuzumaki N. |
| Title | The dominant negative H-ras mutant, N116Y, suppresses growth of metastatic human pancreatic cancer cells in the liver of nude mice. |
| Journal | Gene Ther |
| Abstract |
In pancreatic cancer, the mutation of c-K-ras is a critical event of tumor growth and metastasis. We have previously demonstrated a dominant negative effect of N116Y on the growth of pancreatic cancer cells. To evaluate the potential of N116Y for suppressing the metastatic growth of pancreatic tumor cells, we made a replication-deficient recombinant N116Y adenovirus driven by the carcinoembryonic antigen (CEA) promoter (Ad CEA-N116Y). We demonstrated that the expression of N116Y, growth inhibition, and apoptotic death induction were all specific to pancreatic cancer cell lines (PCI-35 and PCI-43) that were promoter positive, whereas no growth retardation was observed in human embryonic pancreas-derived cell line 1C3D3 after Ad CEA-N116Y infection. We examined the effect of Ad CEA-N116Y on the metastatic growth of PCI-43 colonies in liver, which was generated by tumor injection into the spleen of nude mice. The results showed that Ad CEA-N116Y effectively reduced the number of metastatic colonies without any complication by injecting intrasplenically 5 days after tumor cell inoculation. Thus, N116Y can selectively suppress the metastatic growth of pancreatic tumor cell by using the CEA promoter-driven adenovirus vector indicating that N116Y gene therapy may be potentially useful for the treatment of pancreatic cancer patients with liver micrometastasis. |
| Volume | 7(6) |
| Pages | 518-26 |
| Published | 2000-3-1 |
| DOI | 10.1038/sj.gt.3301125 |
| PMID | 10757026 |
| MeSH | Adenoviridae / genetics Animals Apoptosis Carcinoembryonic Antigen / genetics Cell Line Gene Expression Genes, Dominant* Genes, ras* Genetic Therapy / methods* Genetic Vectors / administration & dosage Humans Injections Liver Neoplasms / physiopathology Liver Neoplasms / secondary* Liver Neoplasms / therapy* Male Mice Mice, Nude Mutation Pancreatic Neoplasms / physiopathology Pancreatic Neoplasms / therapy* Reverse Transcriptase Polymerase Chain Reaction Spleen |
| IF | 4.128 |
| Times Cited | 36 |
| WOS Category | MEDICINE, RESEARCH & EXPERIMENTAL BIOTECHNOLOGY & APPLIED MICROBIOLOGY GENETICS & HEREDITY BIOCHEMISTRY & MOLECULAR BIOLOGY |
| Altmetric score |
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | 1C3D3(RCB0796) |