Detection of free peritoneal cancer cells in gastric cancer using cancer-specific Newcastle disease virus Journal Article


Authors: Wong, J.; Schulman, A.; Kelly, K.; Zamarin, D.; Palese, P.; Fong, Y.
Article Title: Detection of free peritoneal cancer cells in gastric cancer using cancer-specific Newcastle disease virus
Abstract: Introduction: Cytologic detection of peritoneal gastric cancer cells by Papanicolaou staining offers important prognostic information but has low sensitivity. We evaluated a novel detection technique using Newcastle disease virus expressing the enhanced green fluorescent protein (NDV-GFP) gene. Methods: NDV-GFP was tested on MKN-1 human gastric adenocarcinoma cells plated upon rat hepatocytes to determine tumor-specific infection and GFP expression. Malignant ascites infected with increasing doses of virus was evaluated for NDV-GFP dose determination. Peritoneal lavage samples from 30 patients with gastric adenocarcinoma undergoing staging laparoscopy were evaluated with NDV-GFP. Results: NDV-GFP can specifically detect one MKN-1 cell among one million benign rat hepatocytes. NDV-GFP at 5 × 10<sup>6</sup> plaque-forming units (PFU) produced optimal GFP expression in malignant ascites. Noncancerous cells were non-GFP expressing. GFP-expressing cells counterstained positive for carcinoembryonic antigen expression, confirming their cancerous origin. Furthermore, in patients with advanced gastric cancer, GFP expression was markedly enhanced over cytology. Of six patients with M1 disease discovered during laparoscopy, only 50% were cytology positive. All six, however, were NDV-GFP positive. Cytology was positive in 9% of patients with T3 disease, 8% with N1 disease, and 50% with N2 disease. In contrast, NDV-GFP was positive in 95% of T3 patients and 100% of patients with N1 or N2 disease. Conclusions: NDV-GFP can specifically infect and detect peritoneal gastric cancer cells and offers a more sensitive method compared with conventional cytology. This novel modality may offer enhanced detection of intraperitoneal cancer spread and provide important prognostic information. © 2009 The Society for Surgery of the Alimentary Tract.
Keywords: genetics; adenocarcinoma; animal; animals; cells, cultured; hepatocytes; metastasis; peritoneal neoplasms; peritoneum lavage; carcinoembryonic antigen; green fluorescent protein; pathology; cell line, tumor; fluorescent antibody technique; diagnostic agent; cell culture; tumor cell line; rat; green fluorescent proteins; fluorescence microscopy; microscopy, fluorescence; rats; detection; liver cell; rats, sprague-dawley; stomach neoplasms; peritoneum tumor; sprague dawley rat; ascitic fluid; stomach tumor; ascites fluid; peritoneal lavage; gastric cancer; newcastle disease virus; enhanced green fluorescent protein; newcastle disease paramyxovirus
Journal Title: Journal of Gastrointestinal Surgery
Volume: 14
Issue: 1
ISSN: 1091-255X
Publisher: Springer  
Date Published: 2010-01-01
Start Page: 7
End Page: 14
Language: English
DOI: 10.1007/s11605-009-1071-8
PUBMED: 19902312
PROVIDER: scopus
PMCID: PMC3269812
DOI/URL:
Notes: --- - Presented at 50th SSAT Annual Meeting at Digestive Disease Week, Chicago, 2009 - "Export Date: 30 November 2010" - "Source: Scopus"
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MSK Authors
  1. Kaitlyn J Kelly
    31 Kelly
  2. Dmitriy Zamarin
    201 Zamarin
  3. Yuman Fong
    775 Fong
  4. Joyce Wong
    16 Wong