JTCS Speed Up Your Browser
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Prasad S. Adusumilli
Valerie W. Rusch
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Adusumilli, P. S.
Right arrow Articles by Fong, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Adusumilli, P. S.
Right arrow Articles by Fong, Y.
Related Collections
Right arrow Pleura

J Thorac Cardiovasc Surg 2006;132:1179-1188
© 2006 The American Association for Thoracic Surgery

General Thoracic Surgery

Intraoperative localization of lymph node metastases with a replication-competent herpes simplex virus

Prasad S. Adusumilli, MDa, David P. Eisenberg, MDa, Brendon M. Stiles, MDa, Sun Chung, MDb, Mei-Ki Chan, BSa, Valerie W. Rusch, MDa, Yuman Fong, MDa,*

a Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY
b Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY.

Received for publication April 6, 2006; revisions received July 7, 2006; accepted for publication July 12, 2006.

* Address for reprints: Yuman Fong, MD, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, New York 10021. (Email: fongy{at}mskcc.org).

OBJECTIVES: Lymph node status is the most important prognostic factor determining recurrence and survival in patients with mesothelioma and other thoracic malignancies. Accurate localization of lymph node metastases is therefore necessary to improve selection of resectable and curable patients for surgical intervention. This study investigates the potential to identify lymph node metastases intraoperatively by using herpes-guided cancer cell–specific expression of green fluorescent protein.

METHODS: After infection with NV1066, a herpes simplex virus carrying green fluorescent protein transgene, human mesothelioma cancer cell lines were assessed for cancer cell–specific infection, green fluorescent protein expression, viral replication, and cytotoxicity. Murine models of lymphatic metastasis were established by means of surgical implantation of cancer cells into the preauricular (drainage to cervical lymph nodes) and pleural (mediastinal and retroperitoneal lymph nodes) spaces of athymic mice. Fluorescent thoracoscopy, laparoscopy, and stereomicroscopy were used to localize lymph node metastases that were confirmed by means of immunohistochemistry.

RESULTS: In vitro NV1066 infected, replicated (5- to 17,000-fold), and expressed green fluorescent protein in all cancer cells, even when infected at a low ratio of one viral plaque-forming unit per 100 tumor cells. In vivo NV1066 injected into primary tumors was able to locate and infect lymph node metastases producing green fluorescent protein that was visualized by means of fluorescent imaging. Histology confirmed lymphatic metastases, and immunohistochemistry confirmed viral presence in regions that expressed green fluorescent protein.

CONCLUSIONS: Herpes virus–guided cancer cell–specific production of green fluorescent protein can facilitate accurate localization of lymph node metastases. Fluorescent filters that detect green fluorescent protein can be incorporated into operative scopes to precisely localize and biopsy lymph node metastases.

Abbreviations and Acronyms CT = computed tomography; GFP = green fluorescent protein; HSV = herpes simplex virus; LN = lymph node; MOI = multiplicity of infection; MPM = malignant pleural mesothelioma; PBS = phosphate-buffered saline; PET = positron emission tomography; RT-PCR = reverse transcriptase–polymerase chain reaction




This article has been cited by other articles:


Home page
 Cancer Res.Home page
Y. Y. Mahller, S. S. Vaikunth, M. C. Ripberger, W. H. Baird, Y. Saeki, J. A. Cancelas, T. M. Crombleholme, and T. P. Cripe
Tissue Inhibitor of Metalloproteinase-3 via Oncolytic Herpesvirus Inhibits Tumor Growth and Vascular Progenitors
Cancer Res., February 15, 2008; 68(4): 1170 - 1179.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
M. J. Liptay
Sentinel Node Mapping in Lung Cancer: The Holy Grail?
Ann. Thorac. Surg., February 1, 2008; 85(2): S778 - S779.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS
Copyright © 2006 by The American Association for Thoracic Surgery.