Effect of regional angiotensin ii infusion on the relationship between tumour blood flow and fluorouracil uptake in a liver metastasis animal model

Dworkin, Michael; Zweit, Jamal; Carnochan, P.; Deehan, B J; Allen-Mersh, T G

doi:10.1016/0959-8049(96)00169-4

Cited by 7 publications

(7 citation statements)

References 15 publications

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“…We have previously suggested (Dworkin et al, 1996) that a significant but transient angiotensin Il-induced TNR increase achieved less chemotherapy advantage during continuous regional fluorouracil infusion than would be predicted by a TNR increase sustained throughout fluorouracil infusion. Assessment of the effects of continuous vasopressor infusion on both tumour-normal blood flow ratio and normal tissue blood flow over the days to weeks involved in clinical regional infusion chemotherapy would be difficult with the methods used in this study.…”

Section: Methodsmentioning

confidence: 99%

“…As chemotherapy uptake is influenced by blood flow (Dworkin et al, 1996), one solution may be to increase tumour and reduce liver parenchymal blood flow by vasoactive manipulation. Previous studies of this strategy have focused on enhancing the tumour-liver parenchymal blood flow ratio (TNR) at a single time point, with the aim of increasing tumour uptake of a bolus chemotherapy dose (Sasaki et al, 1985).…”

mentioning

confidence: 99%

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Effect of continuous regional vasoactive agent infusion on liver metastasis blood flow

Dworkin

Carnochan²,

Allen-Mersh³

1997

Br J Cancer

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Summary Regionally administered vasopressors might increase tumour chemotherapy uptake by differentially constricting normal and tumour blood vessels, leading to a selective increase in blood flow to the tumour. In this study, we compared the effects of the vasopressors angiotensin 11, vasopressin and endothelin and the vasodilator calcitonin gene-related peptide (CGRP) by continuously measuring liver parenchymal and tumour blood flow during a 30-min regional vasoactive infusion in a rat HSN liver metastasis model. Vasopressin and angiotensin 11 produced a vasoconstriction that decreased despite continued infusion, while endothelin infusion led to prolonged vasoconstriction with a more gradual onset. CGRP infusion resulted in increased vessel conductance but a reduction in blood flow due to systemic hypotension. The tumour to normal flow ratio (TNR) was transiently increased during infusion of all pressors, but only endothelin produced sufficient change to result in a rise in average TNR throughout pressor infusion. Continuous liver and tumour blood flow measurement throughout vasoactive infusion demonstrated that the extent and the duration of blood flow change varied with the agents assessed. No vasoactive agent increased tumour blood flow, but endothelin had the most suitable vasoactive properties for enhancing tumour uptake of continuously infused chemotherapy.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Effect of continuous regional vasoactive agent infusion on liver metastasis blood flow

Dworkin

Carnochan²,

Allen-Mersh³

1997

Br J Cancer

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“…It has been observed that the systemic toxicity of HAI is higher in patients with arterial-venous shunts 32 . Attempts have been made to harness therapeutically the absence of continuous smooth muscle layer and autonomic innervations in tumor blood vessels compared to normal arteries 33 , but the results of clinical studies have been disappointing 34,35 . It remains to be determined whether this difference between normal and tumor blood vessels could be exploited in combinations of HAI and targeted agents.…”

Section: Theoretical Foundations Of Haimentioning

confidence: 99%

Hepatic arterial infusion in colorectal carcinoma: is anatomical targeting still relevant in an era of molecularly targeted therapy?

Melichar¹

2012

BIOMED PAP

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Background. Historically, metastatic colorectal carcinoma was regarded as a tumor that is relatively resistant to cytotoxic agents. Due to the limited number of treatment options, methods have been investigated to enhance selectivity. One method for enhancing selectivity is anatomical targeting, including hepatic arterial infusion (HAI). Methods. A comprehensive review of the literature. Results. Early studies with HAI used fluoropyrimidines, 5-fluorouracil or floxuridine. Several randomized trials comparing the HAI of fluoropyrimidines with systemic administration of fluoropyrimidines or best supportive care that were conducted in the 1980s and early 1990s demonstrated a superior objective response rate, but usually not a prolongation of survival in patients treated with HAI. The current standard of first line systemic chemotherapy of metastatic colorectal carcinoma is combination chemotherapy (fluoropyrimidines, oxaliplatin and/or irinotecan) administered with targeted agents. A number of trials have reported promising activity of the HAI of oxaliplatin and/or irinotecan with fluoropyrimidines, but only pilot studies are available for the combination of HAI of cytotoxic agents with targeted drugs. Factors that limit the effectiveness and utilization of HAI include catheter or port system-related complications, the presence of extrahepatic metastases, or increased risk of hepatic toxicity. Conclusions. HAI could be considered in clinical practice in different settings, including patients after liver resection, as second line therapy in patients failing standard front line regimens and as neodjuvant therapy to convert to resectability. Future studies should specifically concentrate on identifying regimens that would result in increased cure rates in patients with isolated hepatic metastases. For this reason, exploiting anatomical selectivity may still be a useful approach, even in the era of targeted therapy.

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“…The animals were anaesthetized and hepatic tumours were produced by mesenteric vein injection of 10 6 HSN cells at laparotomy (7). After a 48-h recovery period, the animals were anaesthetized for a second time and the internal jugular vein cannulated.…”

Section: Tumour Implantation and Pump Insertionmentioning

confidence: 99%

“…Thus a means of increasing tumour chemotherapy uptake without producing parenchymal toxicity is required. Since chemotherapy uptake is in uenced by blood ow (3,7), one approach has been to attempt to increase tumour and reduce liver parenchymal blood ow by vasoactive manipulation (8). However, increases in tumour blood ow have not been achieved with this approach (9), and one reason may be an absence of vessels within hypovascular tumours where blood can be selectively shunted (10) after adjacent normal tissue vasoconstriction.…”

mentioning

confidence: 99%

Basic Fibroblast Growth Factor Infusion Increases Tumour Vascularity, Blood Flow and Chemotherapy Uptake

et al. 2002

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Effect of regional angiotensin ii infusion on the relationship between tumour blood flow and fluorouracil uptake in a liver metastasis animal model

Cited by 7 publications

References 15 publications

Effect of continuous regional vasoactive agent infusion on liver metastasis blood flow

Effect of continuous regional vasoactive agent infusion on liver metastasis blood flow

Hepatic arterial infusion in colorectal carcinoma: is anatomical targeting still relevant in an era of molecularly targeted therapy?

Basic Fibroblast Growth Factor Infusion Increases Tumour Vascularity, Blood Flow and Chemotherapy Uptake

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