Chemoembolization of rat liver metastasis with irinotecan and quantification of tumor cell reduction

Saenger, J.; Leible, Maike; Seelig, Matthias H.; Berger, Martin R.

doi:10.1007/s00432-003-0523-x

Cited by 12 publications

(9 citation statements)

References 42 publications

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“…This application method increases the regional uptake of a coadministered drug and reduces the systemic drug concentration (Ball 1991, Starkhammar andHakansson 1987). Recently it was demonstrated preclinically that HACE enables the locoregional use of drugs without significant first-path effect in the liver (Saenger et al 2004). To date, few clinical studies have shown a benefit in survival following HACE for certain lesions, such as hepatocellular carcinoma (Llovet et al 2002) or liver metastases of colorectal cancer (Lang and Brown, Jr. 1993, Sanz-Altamira et al 1997, Tellez et al 1998).…”

Section: Discussionmentioning

confidence: 97%

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Combination treatment of CC531-lac-Z rat liver metastases by chemoembolization with pemetrexed disodium and gemcitabine

Rodenbach

Eyol

Seelig³

et al. 2005

J Cancer Res Clin Oncol

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A regimen-dependent synergistic combination effect of both drugs was found in vitro. In animals, hepatic artery chemoembolization with GEM was superior to systemic intravenous bolus treatment. Portal vein chemoembolization with MTA was ineffective. The optimal in vitro regimen of MTA (intravenous or PVCE) preceding GEM (HACE) resulted in a maximally additive tumor growth inhibition. The results indicate that MTA and GEM can successfully be combined and favor further evaluation in patients.

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Section: Discussionmentioning

confidence: 97%

“…It was shown that drugs, even without significant first-path effect, such as irinotecan (Saenger et al 2004) or gemcitabine , can be used to reduce the tumor load in the liver more successfully than 5-FU when coadministered with starch microspheres into the hepatic artery (HACE).…”

mentioning

confidence: 99%

Combination treatment of CC531-lac-Z rat liver metastases by chemoembolization with pemetrexed disodium and gemcitabine

Rodenbach

Eyol

Seelig³

et al. 2005

J Cancer Res Clin Oncol

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“…Tumor cell preparation and transplantation were conducted as previously described [12,18,19]. Briefly, for in vivo injection, 4 9 10 6 tumor cells were suspended in 0.2 ml phosphate buffered saline (PBS) without calcium and magnesium ions.…”

Section: In Vivo Inoculationmentioning

confidence: 99%

“…The rat model was chosen as a suitable model for TACE using the DEB, as it was previously demonstrated using this model that there was significant activity of irinotecan in terms of complete remission in 44% of rats and reduction of the mean tumor cell load by 66% [12]. In this model CC53l-lacZ cells are transplanted by portal vein injection into male WAG/Rij rats and detection of tumor cells is accomplished by measuring their b-galactosidase activity.…”

mentioning

confidence: 99%

Chemoembolisation of rat colorectal liver metastases with drug eluting beads loaded with irinotecan or doxorubicin

Eyol

Boleij

Taylor

et al. 2008

Clin Exp Metastasis

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Systemic chemotherapy has limited success in treating liver metastasis of colorectal cancer. Alternative approaches such as hepatic arterial infusion or trans arterial chemoembolisation aim to deliver the chemotherapy locally to address the predominant liver disease. Chemoembolisation with drug eluting beads (DEB) designed to deliver drug at the target over a protracted period of time is a new strategy to reduce the tumor burden of liver metastases. To test this hypothesis, DEB possessing anionic groups capable of ionically complexing with cationic drugs were synthesised by a suspension polymerisation method and were fractionated to produce an average size of 75 microm. The DEB were loaded with the desired concentration of either doxorubicin hydrochloride or irinotecan hydrochloride prior to administration by immersion in the drug solution, yielding essentially 100% loading efficiency. To determine their effect in vivo, a transplantable orthotopic and isogenic rat liver metastasis model was used which is based on intraportal injection of 4 x 10(6) beta-galactosidase transfected CC531 rat colorectal cancer cells into male WAG/Rij rats. By MTT assay, the cells were shown to be sensitive to both drugs in vitro with the IC(50) being by two orders of magnitude lower for doxorubicin (110 nM after 72 h) compared to irinotecan (25 microM after 72 h). For the in vivo phase, a differential expression of the ERK MAP kinase between tumor cells cultured in vitro and those inoculated in vivo was noted using Western blotting techniques. This was considered to be indicative of passage-induced cell senescence that reduced the sensitivity of the tumor cells to DEB chemoembolisation. This notwithstanding, administration of DEB loaded with irinotecan or doxorubicin by single injection into the hepatic artery showed significant anticancer activity, as measured by a reduction in the tumor burden of the liver and a corresponding reduction in liver weight. Comparing the two agents, irinotecan appears more advantageous because of its significant activity and excellent tolerability following administration at two dosages of either 20 or 30 mg/kg. Doxorubicin showed a narrower window of activity, being effective at 4 mg/kg but ineffective at the lower dose of 2 mg/kg. We conclude that chemoembolisation with DEB with either agent may have potential for treating patients with colorectal liver metastasis, although irinotecan DEB appeared to have a more favourable safety profile.

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“…Thus, the comparison of HACE with 5-FU or Gem showed that the efficacy of Gem in reducing the hepatic tumor cell load was significantly higher and its therapeutic ratio was greater than that of 5-FU. In a subsequent experiment, the effect of HACE with irinotecan was compared vs. 5-FU as a standard agent in rat liver metastasis (Saenger, et al, 2004). Briefly, 4 × 10 6 CC531-lac-Z cells were intraportally injected into male Wag/Rij rats.…”

Section: Generation Of the Modelmentioning

confidence: 99%

Experimental Colorectal Cancer Liver Metastasis

Georges¹,

Adwan²,

Berger³

2012

Colorectal Cancer - From Prevention to Patient Care

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Chemoembolization of rat liver metastasis with irinotecan and quantification of tumor cell reduction

Abstract: In conclusion, the effect of HACE with irinotecan surpassed that of HACE with 5-FU and prompts further investigation in clinical trials.

Cited by 12 publications

References 42 publications

Combination treatment of CC531-lac-Z rat liver metastases by chemoembolization with pemetrexed disodium and gemcitabine

Combination treatment of CC531-lac-Z rat liver metastases by chemoembolization with pemetrexed disodium and gemcitabine

Chemoembolisation of rat colorectal liver metastases with drug eluting beads loaded with irinotecan or doxorubicin

Experimental Colorectal Cancer Liver Metastasis

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