Regional administration of oncolytic Echovirus 1 as a novel therapy for the peritoneal dissemination of gastric cancer
| Autor: | Brian R. Carlton, Gough G. Au, Richard D. Barry, Darren R. Shafren, Erin S. Haley |
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| Rok vydání: | 2008 |
| Předmět: |
Pathology
medicine.medical_specialty Mice SCID Transfection Mice Peritoneum Stomach Neoplasms Cell Line Tumor Drug Discovery medicine Animals Humans Virotherapy Stomach cancer Luciferases Genetics (clinical) Peritoneal Neoplasms Oncolytic Virotherapy Mice Inbred BALB C business.industry Cancer medicine.disease Flow Cytometry Survival Analysis Xenograft Model Antitumor Assays Oncolytic virus Enterovirus B Human Tumor Burden Oncolytic Viruses medicine.anatomical_structure Lytic cycle Cancer cell Luminescent Measurements Cancer research Molecular Medicine Female Integrin alpha2beta1 Ovarian cancer business |
| Zdroj: | Journal of molecular medicine (Berlin, Germany). 87(4) |
| ISSN: | 1432-1440 |
| Popis: | The dissemination of malignant gastric cells to the peritoneum occurs frequently, usually as an early event in disease, and results in poor patient prognosis. Surgery and chemotherapy offer limited therapeutic success. The low-pathogenic human enterovirus, Echovirus 1 (EV1), is an oncolytic virus that selectively targets and destroys malignant prostate and ovarian cancer xenografts in vivo. Lytic EV1 infection requires the cell surface expression of alpha(2)beta(1), an integrin involved in the dissemination of gastric cancer cells to the peritoneum. Herein, we evaluated the capacity of EV1 for anti-neoplastic cell action in gastric peritoneal carcinomatosis. Flow cytometric analysis demonstrated that alpha(2)beta(1) was abundantly surface expressed on a panel of gastric cancer cell lines, rendering the majority of lines highly susceptible to in vitro lytic EV1 infection and supportive of efficient viral progeny production. A bioluminescent MKN-45-Luc SCID mouse model of peritoneal dissemination was developed to allow real-time non-invasive monitoring of peritoneal tumor burden. Employing this mouse model, we demonstrated a therapeutic dose-response for escalating oncolytic EV1 doses. Taken together, these results emphasize the exciting potential for EV1 as a single or adjunct therapy for the control of the peritoneal dissemination of gastric cancer. |
| Databáze: | OpenAIRE |
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