Gamma linolenic acid and other fatty acids in the treatment of pancreatic carcinoma
Gamma linolenic acid and other fatty acids in the treatment of pancreatic carcinoma
Most patients with carcinoma of the pancreas present late with advanced disease for whom there is no effective chemotherapy. Essential fatty acids (EFA) such as gamma linolenic acid (GLA) and eicosapentaenoic acid (EPA) have shown promise as antitumour agents in previous in vitro, animal and also in some clinical studies. The main advantage is virtual absence of side effects, thus the quality of life is not impaired. Here the aim was mainly to evaluate GLA as an anticancer agent in pancreatic carcinoma. EPA was also studied to a limited extent.
The effect of lithium salt of GLA (LiGLA) and 1-γlinolenyl-3-eicosapentaenoyl propane diol against human pancreatic carcinoma cell lines in vitro was tested by incubating these cells with these compounds for 7 days. The influence of iron and albumin on the effect of LiGLA was also studied. In vivo evaluation was carried out in nude mice injected with a human pancreatic cancer cell line and treated with various preparations of GLA and EPA. In the clinical study 278 patients with advanced irresectable pancreatic carcinoma were treated with LiGLA.
LiGLA had a dose and time dependent growth inhibitory effect on human pancreatic cancer in vitro. Albumin reduced while free iron but not transferrin-bound iron promoted this effect. Similarly 1-γ-linolenyl-3-eicosapentaenoyl propane diol was also growth inhibitory in vitro. No antitumour effect or a change in tumour lipid fatty acid composition was seen in nude mice with human pancreatic tumours produced with the same cell line which was sensitive in vitro, and treated with the maximum tolerated doses of LiGLA ip or iv or lithium salt of EPA ip. Intra-tumour injection of LiGLA was, however, effective. 1-γ-linolenyl-3-eicosapentaenoyl propane diol was also not growth inhibitory in nude mice, and tumour fatty acid composition was unchanged. Concurrent administration of parenteral iron with this compound did not significantly improve the skills. IV LiGLA in pancreatic cancer patients had no severe side effects and inhibited the acute phase response but was ineffective in prolonging survival.
It is difficult to achieve tumour growth inhibition and prolongation of survival in pancreatic carcinoma with EFA's using conventional means of administration. Locoregional therapy may be more effective in this regard.
University of Southampton
Ravichandran, Duraisamy
2a465ec1-0d73-4eb7-b07b-46597d4a4443
1998
Ravichandran, Duraisamy
2a465ec1-0d73-4eb7-b07b-46597d4a4443
Ravichandran, Duraisamy
(1998)
Gamma linolenic acid and other fatty acids in the treatment of pancreatic carcinoma.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
Most patients with carcinoma of the pancreas present late with advanced disease for whom there is no effective chemotherapy. Essential fatty acids (EFA) such as gamma linolenic acid (GLA) and eicosapentaenoic acid (EPA) have shown promise as antitumour agents in previous in vitro, animal and also in some clinical studies. The main advantage is virtual absence of side effects, thus the quality of life is not impaired. Here the aim was mainly to evaluate GLA as an anticancer agent in pancreatic carcinoma. EPA was also studied to a limited extent.
The effect of lithium salt of GLA (LiGLA) and 1-γlinolenyl-3-eicosapentaenoyl propane diol against human pancreatic carcinoma cell lines in vitro was tested by incubating these cells with these compounds for 7 days. The influence of iron and albumin on the effect of LiGLA was also studied. In vivo evaluation was carried out in nude mice injected with a human pancreatic cancer cell line and treated with various preparations of GLA and EPA. In the clinical study 278 patients with advanced irresectable pancreatic carcinoma were treated with LiGLA.
LiGLA had a dose and time dependent growth inhibitory effect on human pancreatic cancer in vitro. Albumin reduced while free iron but not transferrin-bound iron promoted this effect. Similarly 1-γ-linolenyl-3-eicosapentaenoyl propane diol was also growth inhibitory in vitro. No antitumour effect or a change in tumour lipid fatty acid composition was seen in nude mice with human pancreatic tumours produced with the same cell line which was sensitive in vitro, and treated with the maximum tolerated doses of LiGLA ip or iv or lithium salt of EPA ip. Intra-tumour injection of LiGLA was, however, effective. 1-γ-linolenyl-3-eicosapentaenoyl propane diol was also not growth inhibitory in nude mice, and tumour fatty acid composition was unchanged. Concurrent administration of parenteral iron with this compound did not significantly improve the skills. IV LiGLA in pancreatic cancer patients had no severe side effects and inhibited the acute phase response but was ineffective in prolonging survival.
It is difficult to achieve tumour growth inhibition and prolongation of survival in pancreatic carcinoma with EFA's using conventional means of administration. Locoregional therapy may be more effective in this regard.
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Published date: 1998
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Local EPrints ID: 463631
URI: http://eprints.soton.ac.uk/id/eprint/463631
PURE UUID: ee73b52c-b156-4887-ab52-0168eb8d1a4a
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Date deposited: 04 Jul 2022 20:54
Last modified: 23 Jul 2022 02:15
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Author:
Duraisamy Ravichandran
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