The effects of intra-arterial vasoconstrictors on the distribution of a radiolabelled low molecular weight marker in an experimental model of liver tumour

Hemingway, D.; Cooke, TG; Chang, David; Grime, S.; Jenkins, S. A.

doi:10.1038/bjc.1991.118

Cited by 28 publications

(8 citation statements)

References 12 publications

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“…Neben der Gabe von abbaubaren Stärkepartikeln sowie Noradrenalin und Angiotensin II, welche vor allem die Perfusion der nicht tumorbefallenen Restleber einschränken [12,32], kann dies auch [24]. Neben der Gabe von abbaubaren Stärkepartikeln sowie Noradrenalin und Angiotensin II, welche vor allem die Perfusion der nicht tumorbefallenen Restleber einschränken [12,32], kann dies auch [24].…”

Section: Pharmakologische Grundlagenunclassified

Die Stellung der regionalen Langzeitchemotherapie bei Lebermetastasen

Lorenz

Staib-Sebler

Gog

et al. 1999

Chirurg

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In numerous tumors, metastasis can be limited to the liver. In non-resectable patients, regional treatment modalities, especially arterial cytostatic infusion, are favored in contrast to systemic chemotherapy, whereas intraportal or intraperitoneal application is not successful. Improved results with high response rates have been reported after development of intra-arterial (i.a.) long-term regimens with FUdR in patients with colorectal liver metastases using implantable pumps and ports. However, a survival benefit could only be demonstrated in comparison with a control group only treated symptomatically. Because of several reports on major local toxicity of i.a. FUdR treatment (i.e. chemical hepatitis and biliary sclerosis) several other effective i.a. 5-FU regimens have been developed. A randomized study has demonstrated superiority of i.a. 5-FU versus i.a. FUdR. In comparison with systemic treatment, superiority has only been demonstrated in patients with an intrahepatic tumor burden of < 25%. Publications about regional treatment of patients with breast, gastric cancer or carcinoid liver metastases are rare. Despite the high response rates reported, the benefit of arterial chemotherapy remains questionable. Overall, local long-term chemotherapy cannot be recommended outside of studies as a primary treatment. However, extensive experience and new drugs support the idea of conducting further regional studies.

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Section: Pharmakologische Grundlagenunclassified

Die Stellung der regionalen Langzeitchemotherapie bei Lebermetastasen

Lorenz

Staib-Sebler

Gog

et al. 1999

Chirurg

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“…A randomised trial has suggested that HAI chemotherapy improves the survival rate compared with untreated controls (Hunt et al, 1990). There is some evidence that co-administration of vasoactive agents such as angiotensin II (AT II) can improve the efficacy of HAI chemotherapy (Goldberg et al, 1991;Hemingway et al, 1991a). However, Sasaki et al (1985) have shown that AT II reaches the peak of its action at about 100 s from the start of the infusion.…”

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confidence: 99%

The absence of autonomic perivascular nerves in human colorectal liver metastases

Ashraf

Crowe²,

Loizidou³

et al. 1996

Br J Cancer

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Summary The peptidergic/aminergic innervation of normal liver and tumour blood vessels was investigated in order to determine vascular control with a view to improving the efficacy of hepatic arterial cytotoxic infusion in the treatment of colorectal liver metastases. Selected areas of liver metastases and macroscopically normal liver from resection specimens (n= 13) were studied using light microscope immunohistochemistry for the presence of protein gene product 9.5 (PGP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), substance P (SP) and tyrosine hydroxylase (TH). The ultrastructure of blood vessels supplying liver metastases and their perivascular innervation were also examined by transmission electron microscopy. In the normal liver, perivascular immunoreactive nerve fibres containing PGP, NPY and TH were observed around the interlobular blood vessels and along the sinusoids and the central vein of the hepatic lobule. The greatest density of immunoreactive nerve fibres was seen for PGP, followed (in decreasing order) by NPY and TH. VIP, SP and CGRP immunoreactivity was observed only in nerve bundles associated with the large interlobular blood vessels. In contrast, no perivascular immunoreactive nerves were observed in colorectal liver metastases. Electron microscopy confirmed the absence of perivascular nerves in liver metastases. In addition, it showed that the walls of these blood vessels were composed of a layer of endothelial cells surrounded by an incomplete or, very rarely in the periphery of the tumour, a complete, layer of synthetic phenotype of smooth muscle-like cells. These results imply that the blood vessels supplying liver metastases are bereft of normal neuronal regulation; whether there is a role for endothelial cell control of blood flow in these vessels is not yet known.

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“…Local intra-arterial administration of angiotensin II to hepatic tumours and liver metastases also has potential for improving regional chemotherapy of these tumours (Sasaki et al, 1985;Hemingway et al, 1991 andGoldberg et al, 1991 (Hori et al, 1985;Burton et al, 1985). Trotter et al (1991) One of the tail vein catheters was fitted with a T-piece connector allowing two syringes to be connected to it.…”

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Modification of tumour blood flow using the hypertensive agent, angiotensin II

Tozer

Shaffi²

1993

Br J Cancer

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Summary The effects of different doses of angiotensin 11 (0.02 to 0.5 jlg kg-' min-' on mean arterial blood pressure, tissue blood flow and tissue vascular resistance were investigated in BD9 rats. Blood flow was measured using the uptake of 12511 or 4C-labelled iodoantipyrine ('25I-IAP and '4C-IAP). Spatial heterogeneity of blood flow within tumours, before and after angiotensin II infusion, was also measured using '4C-IAP and an autoradiographic procedure. Mean arterial blood pressure rose steeply with angiotensin II dose. Blood flow to skeletal muscle, skin overlying the tumour, contralateral skin, small intestine and kidney tended to decline in a dose-dependent manner. Blood flow to the tumour was also reduced (to 80% of control values) but there was no dose response. Blood flow to the heart was slightly increased and blood flow to the brain was unaffected by angiotensin II. Vascular resistance, in all tissues, was increased by angiotensin II infusion. The increase in tumour tissue was similar to that found in skeletal muscle and small intestine and is likely to be caused by a direct vasoconstricting effect of the drug rather than autoregulation of tumour blood flow in the face of an increase in perfusion pressure. The reduction in overall blood flow at the highest perfusion pressure was due to a preferential effect of angiotensin II at the tumour periphery. These results show that some tumours, at least, can respond directly to the effects of vasoactive agents.

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The effects of intra-arterial vasoconstrictors on the distribution of a radiolabelled low molecular weight marker in an experimental model of liver tumour

Cited by 28 publications

References 12 publications

Die Stellung der regionalen Langzeitchemotherapie bei Lebermetastasen

Die Stellung der regionalen Langzeitchemotherapie bei Lebermetastasen

The absence of autonomic perivascular nerves in human colorectal liver metastases

Modification of tumour blood flow using the hypertensive agent, angiotensin II

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