Dormant liver metastases: an experimental study

Panís, Yves; Ribeiro, J. L.; Chrétien, Yves; Nordlinger, Bernard

doi:10.1002/bjs.1800790309

Cited by 132 publications

(64 citation statements)

References 28 publications

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“…Local and distant recurrences after surgical therapy for colorectal as well as hepatocellular cancer, occur as a result of microscopic disease that was not detectable at the time of resection (31). A number of conventional strategies including chemotherapy and radiation therapy have had little or no impact on improving recurrence rates and survival (32)(33)(34)(35)(36)(37)(38).…”

Section: Discussionmentioning

confidence: 99%

Use of an oncolytic virus secreting GM-CSF as combined oncolytic and immunotherapy for treatment of colorectal and hepatic adenocarcinomas

Malhotra

Kim

Zager

et al. 2007

Surgery

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Oncolytic cancer therapy using herpes simplex viruses (HSV) that have direct tumoricidal effects and cancer immunotherapy using the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) have each been effective in preclinical testing. NV1034 is a multi-mutated oncolytic HSV carrying the gene for murine GM-CSF that attempts to combine these two anticancer strategies. The purpose of this study was to compare NV1034 to NV1023, the parent HSV mutants lacking GM-CSF, in order to determine if such combined oncolytic and immunotherapy using a single vector has advantages over oncolytic therapy alone. In vitro, expression GM-CSF did not alter the infectivity, in vitro cytotoxicity, or replication of NV1034 compared to the non-cytokine secreting control. Tumors infected with NV1034 produced GM-CSF in picogram quantities. In vivo efficacy of the viruses against murine colorectal carcinoma CT26 and murine hepatoma Hepa l-6 was then tested in subcutaneous tumors in syngeneic Balb/c and C57 L/J mice respectively. In these immune competent models, NV1034 or NV1023 each demonstrated potent antitumor activity. Treatment with NV1034 had significantly better antitumor effect compared to treatment with NV1023. Furthermore, in mice depleted of CD4+ and CD8+ T-lymphocytes, there was no difference in the antitumor efficacy of these viruses. Viral vectors combining oncolytic and immunotherapy are promising agents in treatment of colorectal carcinoma and hepatoma.

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Section: Discussionmentioning

confidence: 99%

Use of an oncolytic virus secreting GM-CSF as combined oncolytic and immunotherapy for treatment of colorectal and hepatic adenocarcinomas

Malhotra

Kim

Zager

et al. 2007

Surgery

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“…Currently, with the advances in diagnostic methods and new therapies, resectability rates have increased [24]. Apart from conversional chemotherapy, portal vein embolization, two-stage resection, and tumor ablation are effective approaches to improve resectability for initially unresectable patients.…”

Section: Introductionmentioning

confidence: 99%

Assessment of Tumor Response and Resection Rates in Unresectable Colorectal Liver Metastases Following Neoadjuvant Chemotherapy with Cetuximab

Somashekhar

Ashwin

Zaveri

et al. 2015

Indian J Surg Oncol

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To investigate efficacy and safety of cetuximab combined with neo adjuvant chemotherapy regimen in patients with unresectable colorectal liver. This was a prospective trial with rate of Ro liver metastases resection as primary end point. Between January 2010 and December 2014, 46 patients with unresectable liver metastases from colon or rectum were enrolled. Patients received Cetuximab along with neoadjuvant chemotherapy where 34 (74 %) and 12 (26 %) patients received FOLFOX and FOLFIRI, respectively. They were assessed for response after 2-3 cycles by CT scan. Patients with resectable disease were offered liver surgery within 3-6 weeks of the last treatment cycle. The primary end point was resection rate of liver metastases, which was evaluated in all patients. Secondary end points were response rate according to Response evaluation criteria in solid tumors (RECIST) criteria, perioperative morbidity and mortality. An objective response was observed in 28 (60.9 %) patients. Seven (15.2 %) patients were reported radiologically to have a complete response (CR); 21 (45.7 %) patients had radiological partial response (PR). An additional 12 patients (26.1 %) demonstrated stable disease (SD) and only six patients (13.0 %) had disease progression (PD). Microscopically complete resections (R0 resection) was performed in all 28 patients (60.9 %). The most frequent toxicities were skin rash and diarrhoea. There was no operative mortality. Chemotherapy with cetuximab yields high response rates compared with historical controls, and leads to significantly increased resectability. Complete resection of previously unresectable colorectal liver metastases can be performed with minimal morbidity and mortality. This therapeutic strategy involves a multimodal approach.

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“…IAA can be oxidized by HRPC to produce cytotoxin to induce tumor cell death. As mammalian peroxidases are not able to oxidize IAA, 26 we did not find any tissue damage in normal organs in mice with this treatment.…”

Section: Discussionmentioning

confidence: 45%

“…25 For patients with unresectable liver metastases, palliative treatment, such as chemotherapy, yields clinical response in only one-third of cases. 26 Thus, alternative therapy is needed for both resectable and unresectable liver tumors.…”

Section: Discussionmentioning

confidence: 99%

Tumor-targeted gene therapy using Adv-AFP-HRPC/IAA prodrug system suppresses growth of hepatoma xenografted in mice

et al. 2011

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Clinical efficacy of current therapies for hepatocellular carcinoma (HCC) treatment is limited. Indole-3-acetic acid (IAA) is non-toxic for mammalian cells. Oxidative decarboxylation of IAA by horseradish peroxidase (HRP) leads to toxic effects of IAA. The purpose of this study was to investigate the effects of a novel gene-targeted enzyme prodrug therapy with IAA on hepatoma growth in vitro and in vivo mouse hepatoma models. We generated a plasmid using adenovirus to express HRP isoenzyme C (HRPC) with the HCC marker, alpha-fetoprotein (AFP), as the promoter (pAdv-AFP-HRPC). Hepatocellular cells were infected with pAdv-AFP-HRPC and treated with IAA. Cell death was detected using MTT assay. Hepatoma xenografts were developed in mice by injection of mouse hepatoma cells. The size and weight of tumors and organs were evaluated. Cell death in tumors was assessed using hematoxylin and eosin-stained tissue sections. HRPC expression in tissues was detected using Reverse Transcriptase-Polymerase Chain Reaction. IAA stimulated death of hepatocellular cells infected with pAdv-AFP-HRPC, in a dose-and time-dependent manner, but not in control cells. Growth of hepatoma xenografts, including the size and weight, was inhibited in mice treated with pAdv-AFP-HRPC and IAA, compared with that in control group. pAdv-AFP-HRPC/IAA treatment induced cell death in hepatoma xenografts in mice. HRPC gene expressed only in hepatoma, but not in other normal organs of mice. pAdv-AFP-HRPC/IAA treatment did not cause any side effects on normal organs. These findings suggest that pAdv-AFP-HRPC/IAA enzyme/prodrug system may serve as a strategy for HCC therapy.

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Dormant liver metastases: an experimental study

Cited by 132 publications

References 28 publications

Use of an oncolytic virus secreting GM-CSF as combined oncolytic and immunotherapy for treatment of colorectal and hepatic adenocarcinomas

Use of an oncolytic virus secreting GM-CSF as combined oncolytic and immunotherapy for treatment of colorectal and hepatic adenocarcinomas

Assessment of Tumor Response and Resection Rates in Unresectable Colorectal Liver Metastases Following Neoadjuvant Chemotherapy with Cetuximab

Tumor-targeted gene therapy using Adv-AFP-HRPC/IAA prodrug system suppresses growth of hepatoma xenografted in mice

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