Arterial chemoembolization with mitomycin C microcapsules in the treatment of primary or secondary carcinoma of the kidney, liver, bone and intrapelvic organs

Kato, Takumi; Nemoto, Ryosuke; Mori, Hisashi; Takahashi, Manabu; Harada, Masaoki

doi:10.1002/1097-0142(19810801)48:3<674::aid-cncr2820480303>3.0.co;2-e

Cited by 82 publications

(33 citation statements)

References 16 publications

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“…The microspheres thus formed were stabilised with glutaraldehyde. After mesh infiltration and differential centrifugation, microspheres of the appropriate size were obtained (Lee et al, 1981;Willmott et al, 1985). The particles were then labelled with '"'I using the Chloramine T method (Hunter & Greenwood, 1962).…”

Section: Methodsmentioning

confidence: 99%

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The use of angiotensin II as a potential method of targeting cytotoxic microspheres in patients with intrahepatic tumour

Goldberg

Murray²,

Kerr³

et al. 1991

Br J Cancer

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Summary Cytotoxic microspheres have been developed for intra-arterial use in patients with liver metastases. Following injection, the distribution of microspheres reflects the pattern of hepatic arterial blood-flow. Vasoactive agents, such as angiotensin II, by producing vasoconstriction in normal liver, might divert arterial blood toward tumour and thereby enhtance the delivery of drug-loaded particles. Using a double isotope technique, the distribution of radiolablled microspheres to tumour and normal liver tissue was measured before and after angiotensin II infusion in nine patients with multiple liver metastases. The median increase in tumour: normal ratio following angiotensin II infusion was by a factor of 2.8 (range 0.8-11.7, P<0.05). This novel approach to regional chemotherapy, using a combination of angiotensin II infusion and cytotoxic microspheres, increases the exposure of tumour to cytotoxic agents and may, therefore, enhance tumour response rates.Sixty percent of patients dying after resection of colorectal cancer are known to have liver metastases at the time of death (Welch & Donaldson, 1979;Ridge & Daly, 1985). The results of systemic chemotherapy have been disappointing; escalation of dose or multi-drug regimes may increase the response rate but are associated with unacceptable toxicity.It is known that liver metastases derive their blood-supply predominantly from the hepatic artery (Ridge et al., 1987) and attention has therefore turned to the concept of regional chemotherapy. In theory, the administration of cytotoxic drugs via the hepatic artery should increase drug levels within the tumour while minimising systemic toxicity (Kato et al., 1981). To date, however, improved survival following bolus intra-hepatic arterial chemotherapy has not been demonstrated (Malik & Wrigley, 1988; Allen-Mersh, 1989). This may be because, following bolus injection, the tumour-bearing liver is exposed to high drug levels only transiently (Goldberg et al., 1988).One means of retaining anti-cancer agents more effectively within the liver might be to load the active agent into embolising particles. There have been reports of chemotherapeutic agents such as adriamycin and mitomycin C being carried in biodegradable particles which act as slowrelease systems when administered via the hepatic artery (McArdle et al., 1988;Fujimoto et al., 1985). Unfortunately, the distribution of arterially administered particles reflects the pattern of arterial blood-flow within the liver, and the proportion of drug reaching hypovascular tumours will be low.Previous studies in animal models have suggested that vasoactive agents such as noradrenaline and angiotensin II modify the pattern of arterial blood-flow by causing temporary arteriolar constriction in normal blood-vessels (Burton et al., 1985). Hepatic tumour vasculature is immature, possessing neither smooth muscle nor an adrenergic nerve supply, and is therefore unable to respond to arterio-constrictors in the same way as normal vasculature (Hafstrom et al., 1980;Mattson et a...

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Section: Methodsmentioning

confidence: 99%

“…In theory, the administration of cytotoxic drugs via the hepatic artery should increase drug levels within the tumour while minimising systemic toxicity (Kato et al, 1981). To date, however, improved survival following bolus intra-hepatic arterial chemotherapy has not been demonstrated (Malik & Wrigley, 1988; Allen-Mersh, 1989).…”

mentioning

confidence: 99%

The use of angiotensin II as a potential method of targeting cytotoxic microspheres in patients with intrahepatic tumour

Goldberg

Murray²,

Kerr³

et al. 1991

Br J Cancer

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“…However, microcapsules containing mitomycin-C have been reported to cause occasionally incurable skin ulcers as a side effect (Kato et al, 1981). The use of this drug, therefore was contraindicated for tumours of the head and neck.…”

Section: Clinical Studymentioning

confidence: 99%

Arterial chemoembolization with cisplatin microcapsules

Okamoto¹,

Konno²,

Togawa³

et al. 1986

Br J Cancer

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Summary Cisplatin (CDDP) was microcapsulated with ethylcellulose. Sustained release of CDDP from the microcapsule, particularly non-protein-bound CDDP, which should have antitumour activity, was demonstrated by an in vitro test. Using a bioassay, it was proven that the biological activity of CDDP was not affected by the microencapsulation process.When CDDP-mc were infused into the maxillary artery of patients with carcinoma of the maxillary sinus or oral cavity, the CDDP level in the circulating blood was significantly lower than that of the patients given non-encapsulated CDDP intravenously. However, a significantly higher CDDP concentration in tumour tissue was found in patients treated with CDDP-mc.These results suggest that selective arterial infusion of CDDP-mc could exert intensive topical antitumour effects on lesions through microinfarction effects, and prolonged drug release, with minimum systemic side effects.Cisplatin (CDDP) is one of the most powerful antineoplastic agents and response rates up to 40% in patients with tumours of the testis or ovary, have been demonstrated (Merrin, 1976). CDDP has also been reported to be effective against carcinoma of the head and neck (Wittes, 1977;Muggia, 1980 Using the conventional method of injecting drugs into the artery serving the tumour, the agents flow into the general circulation rapidly, and it is difficult to keep in situ drug concentrations high.Mitomycin-C microcapsule (Mitomycin-C, encapsulated with ethylcellulose) chemoembolization was developed by colleagues (1979, 1981) who showed a significant effect on tumours of the urinary tract and liver.In our study CDDP was encapsulated with ethylcellulose and basic and clinical observations recorded. Materials and methodsEffect of CDDP on L-cell proliferation L-cells derived from mouse fibroblasts were cultivated in MEM (Nishui Co., Ltd.) containing 10% foetal calf serum at 37°C.After treatment with EDTA-trypsin, the cell suspension was adjusted to 5 x 104/tube and cultivated for 24 h at 37°C. The culture media were then exchanged with media containing CDDP (Bristol Co., Ltd.) Encapsulation of CDDP CDDP was encapsulated with ethylcellulose by using the method of coacervation with certain modifications described for mitomycin-C microcapsules (Kato et al., 1978), and sterlilized at 1350C for 2h. CDDP-microcupsules (CDDP-mc) consist of 60% (w/w) CDDP (Bristol Co., Ltd.) as the core, and 40% (w/w) of ethylcellulose as the shell. The dose of CDDP-mc was expressed as the CDDP content. The particle size of CDDP-mc was measured microscopically and the mean value was

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“…Embolization techniques have been used to treat several clinical problems, including treatment of malignant tumors and arteriovenous malformation [16][17][18][19][20] . Transarterial chemoembolization is a medical technique that combines the application of a drug with an embolic agent, leading to local chemical and physical actions during treatment [21][22][23][24] . This encourages the development of techniques intended to load biological molecules onto embolizing polymer microparticles.…”

Section: Introductionmentioning

confidence: 99%

Adsorption of BSA (Bovine Serum Albuminum) and lysozyme on poly(vinyl acetate) particles

Santos¹,

Alves²,

Pinto³

2016

Polímeros

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SbstractPoly(vinyl acetate) (PVAc) particles find many uses in the biomedical field, including the use as particle embolizers. Particularly, embolizing particles can combine physical and chemical effects when they are doped with pharmaceuticals. For this reason, the adsorption of bovine serum albuminum (BSA) and lysozyme (used as model biomolecules) on PVAc particles produced through suspension polymerization is studied in the present manuscript in a broad range of pH values. It is shown that significant amounts of BSA and lysozyme can be adsorbed onto PVAc particles in the vicinities of the isoelectric point of the biomolecules (0.65mg of BSA and 1.0mg of lysozyme per g of PVAc), allowing for production of chemoembolizers through adsorption. Particularly, it is shown that lysozyme still presents residual activity after the adsorption process, which can constitute very important characteristic for real biomedical applications.

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Arterial chemoembolization with mitomycin C microcapsules in the treatment of primary or secondary carcinoma of the kidney, liver, bone and intrapelvic organs

Cited by 82 publications

References 16 publications

The use of angiotensin II as a potential method of targeting cytotoxic microspheres in patients with intrahepatic tumour

The use of angiotensin II as a potential method of targeting cytotoxic microspheres in patients with intrahepatic tumour

Arterial chemoembolization with cisplatin microcapsules

Adsorption of BSA (Bovine Serum Albuminum) and lysozyme on poly(vinyl acetate) particles

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