Improved Resection and Outcome of Colon-Cancer Liver Metastasis with Fluorescence-Guided Surgery Using In Situ GFP Labeling with a Telomerase-Dependent Adenovirus in an Orthotopic Mouse Model

Yano, Shuya; Takehara, Kiyoto; Miwa, Shinji; Kishimoto, Hiroyuki; Hiroshima, Yukihiko; Murakami, Takashi; Urata, Yasuo; Kagawa, Shunsuke; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M.

doi:10.1371/journal.pone.0148760

Cited by 36 publications

(35 citation statements)

References 20 publications

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“…We have previously demonstrated OBP-401-based fluorescence-guided surgery is highly effective in various types of cancers including soft tissue sarcoma [4], glioblastoma [5], pancreatic cancer [6], lung cancer [7], colon cancer-liver metastasis [8], and melanoma [9]. In contrast, conventional bright-light surgery (BLS) could not fully resect these tumors [4–9].…”

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confidence: 99%

Fluorescence-guided surgery of a highly-metastatic variant of human triple-negative breast cancer targeted with a cancer-specific GFP adenovirus prevents recurrence

et al. 2016

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We have previously developed a genetically-engineered GFP-expressing telomerase-dependent adenovirus, OBP-401, which can selectively illuminate cancer cells. In the present report, we demonstrate that targeting a triple-negative high-invasive human breast cancer, orthotopically-growing in nude mice, with OBP-401 enables curative fluorescence-guided surgery (FGS). OBP-401 enabled complete resection and prevented local recurrence and greatly inhibited lymph-node metastasis due to the ability of the virus to selectively label and subsequently kill cancer cells. In contrast, residual breast cancer cells become more aggressive after bright (white)-light surgery (BLS). OBP-401-based FGS also improved the overall survival compared with conventional BLS. Thus, metastasis from a highly-aggressive triple-negative breast cancer can be prevented by FGS in a clinically-relevant mouse model.

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Section: Introductionmentioning

confidence: 99%

Fluorescence-guided surgery of a highly-metastatic variant of human triple-negative breast cancer targeted with a cancer-specific GFP adenovirus prevents recurrence

et al. 2016

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“…We have developed an orthotopic colon-cancer liver metastasis model and have shown improved outcomes after resection using fluorescence labeling (14). Colon cancer liver metastases were modeled by serially selecting for aggressive liver metastasis variants of colon cancer cells after splenic injection.…”

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“…Tumor-specific fluorescence was delivered in situ via viral vector expressing green fluorescent protein (GFP) or a fluorescently labeled antibody. Yano et al and Kishimoto et al used OBP-401, a conditionally replicative adenovirus with the replication cassette under the control of the human telomerase reverse transcriptase (hTERT) promoter and a GFP tag under the control of a cytomegalovirus (CMV) promoter (14,15). Three days after direct intratumoral injection of the adenovirus, a strong GFP signal was present at the tumor site and the fluorescence signal was used for fluorescenceguided surgery (FGS).…”

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Regarding the applications of fusion-fluorescence imaging using indocyanine green in laparoscopic hepatectomy

Lwin

Hoffman

Bouvet

2017

Transl. Gastroenterol. Hepatol.

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A critical concern in performing hepatectomy for tumor resection is determining the boundaries of resection and identifying any additional lesions. Obtaining negative margins has a direct impact on disease-free survival in patients (1). The main goal is to remove neoplastic tissue while sparing sufficient normal parenchyma and preserving organ function. Deciding the location of margins in resection for liver neoplasms is based on the location of tumor. Crosssectional imaging modalities localize the lesion and assist in pre-operative planning, but once in the operating room, the surgeon must rely on visual inspection and tactile feedback along with anatomic knowledge to localize and resect the tumor. In the setting of laparoscopic surgery, this becomes limited as bimanual palpation is no longer possible and tactile feedback becomes limited. This becomes even more so in the setting of robotic surgery as tactile feedback is absent and the surgeon must rely only on visual cues.The use of near-infrared (NIR) fluorescence imaging technology in the operating room has greatly advanced real time intra-operative imaging and target identification. Indocyanine green (ICG), a dye traditionally used for fundoscopy and estimations of cardiac and hepatic function, is a fluorophore that emits a fluorescence signal when excited with near infrared light (750-810 nm) (2). The dye binds to plasma albumin and has been used intra-operatively to evaluate graft perfusion, aneurysm clipping, and lymphatic mapping. ICG undergoes hepatic metabolism and is excreted by hepatocytes into the biliary tract after approximately 6 h. Due to the impaired biliary excretion of hepatic malignancies compared to normal hepatocytes, ICG is preferentially retained in or around these lesions over time, allowing surgeons to visualize the fluorescent signal and identify the tumor over the liver (3).For patients undergoing pre-operative ICG hepatic function testing several days before surgery, surface hepatic lesions can be visualized with a positive fluorescence signal. There is sufficient contrast as the ICG is retained at the lesions and ICG in the surrounding normal hepatocytes will have been excreted out in the biliary tract. The dye is versatile in that it can additionally be used as an angiographic agent when injected into portal vasculature, similar to indigo-carmine or methylene blue (4). Rather than the quick washout of the traditional dyes, the NIR signal from ICG persists throughout the surgical procedure, allowing for continued image guidance. Positive segmental staining can be obtained by selective portal vein injection while negative segmental staining can be obtained by intravenous injection during selective portal clamping. Realtime intra-operative selective segmental staining, along with contrasted-target identification, allows surgeons to more effectively resect hepatic neoplasms.In the article titled "Applications of fusion-fluorescence imaging using indocyanine green in laparoscopic hepatectomy," Terasawa et al. describe the use of ICG-fl...

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“…Our lab has shown that the use of tumor-specific fluorescent organ labeling in laparoscopy aids in rapid and accurate identification of tumors, especially at the sub-millimeter resolution (16). We have also studied FGS with tumor-specific fluorescence in a colon-cancer liver-metastasis model (17,18). Fluorescence was delivered via an anti-CEA antibody or tumor-specific adenovirus vectors expressing GFP.…”

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Fluorescence-guided laparoscopic hepatectomy

Lwin

Sicklick

Hoffinan

et al. 2016

Ann. Laparosc. Endosc. Surg

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Improved Resection and Outcome of Colon-Cancer Liver Metastasis with Fluorescence-Guided Surgery Using In Situ GFP Labeling with a Telomerase-Dependent Adenovirus in an Orthotopic Mouse Model

Cited by 36 publications

References 20 publications

Fluorescence-guided surgery of a highly-metastatic variant of human triple-negative breast cancer targeted with a cancer-specific GFP adenovirus prevents recurrence

Fluorescence-guided surgery of a highly-metastatic variant of human triple-negative breast cancer targeted with a cancer-specific GFP adenovirus prevents recurrence

Regarding the applications of fusion-fluorescence imaging using indocyanine green in laparoscopic hepatectomy

Fluorescence-guided laparoscopic hepatectomy

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