HER2 Support Group Forums - View Single Post - ~Ned Is Over~Aggressive Brain Met Activity~PLEASE READ MY BRAIN SPECIALIST FRIENDS

R.B. · 08-27-2008, 10:14 AM

Beleive51,

I hope your 1000th post is better news. I am so sorry to read your news.

This sounds so trite but every little helps.

Below I copy a trial which suggests there is evidence that brain tumours show a fatty acid imbalance and have a higher fat uptake than normal cells. There is also limited evidence Omega 6 may promote growth and DHA and EPA reduce it through Cox2. Uptake will reflect a combination of dietary and stored fats.

So food for thought as to whether it is worth increasing long chain Omega 3s (fish Oil) and reduce omega 6s (primarily the common vegetable oils sunflower, soy, grapeseed etc) which are found in lots of foods.

Infusion is a way of getting the DHA EPA to the body more quickly and there have been some trials in cancers.

Clearly it is essential to discuss dietary change with your doctors and more so in treatment. They may find the trials thought provoking if nothing else.

I am sorry I cannot be more specific but there appears to be only a limited amount of research on the subject. The Greek Diet Thread has much more on the impact of Omega 6 and 3 on BC if you have not already seen it. http://her2support.org/vbulletin/showthread.php?t=24410

RB

This is a link to a search on NCBI for brain tumour and DHA.
http://www.ncbi.nlm.nih.gov/sites/en...%20tumor%20DHA

1: Lipids. 1996 Dec;31(12):1283-8.Links
The fatty acid composition of human gliomas differs from that found in nonmalignant brain tissue.
Martin DD, Robbins ME, Spector AA, Wen BC, Hussey DH.

Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City 52242, USA.

To compare the fatty acid composition of tumor tissue from glioma patients with that of normal brain tissue, tissue samples were obtained from 13 glioma patients and from 3 nonmalignant patients. Following lipid extraction, total fatty acid composition was measured using gas-liquid chromatography. samples were further separated into phospholipids and neutral lipids. Representative samples were then separated into phospholipid classes by thin-layer chromatography and the fatty acid composition assayed. Levels of the polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA), were significantly reduced (P = 0.029) in the glioma samples compared with normal brain samples; mean values were 4.8 +/- 2.9% and 9.2 +/- 1.0%, respectively. This reduction in glioma DHA content was also observed in terms of phospholipids (4.6 +/- 2.1% vs. 9.6 +/- 0.8%, P = 0.002). The phosphatidylserine and phosphatidylethanolamine phospholipid classes were reduced in the glioma samples. Differences were also noted in the n-6 PUFA content between glioma and normal brain samples. The glioma content of the n-6 PUFA linoleic acid was significantly greater (P < 0.05) than that observed in the control samples in terms of total lipids. Thus, the fatty acid composition of human gliomas differs from that found in nonmalignant brain tissue.

1: Clin Exp Metastasis. 1993 Mar;11(2):141-9.Links
Intravenously injected radiolabelled fatty acids image brain tumour phospholipids in vivo: differential uptakes of palmitate, arachidonate and docosahexaenoate.
Nariai T, Greig NH, DeGeorge JJ, Genka S, Rapoport SI.

Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892.

This paper investigates the incorporation of intravenously (i.v.) administered radiolabelled fatty acids--[9,10(3)-H]palmitate (3H-PA), [1-14C]arachidonate (14C-AA) and [1-14C]docosahexaenoate (14C-DHA)--into intracerebrally implanted tumours in awake Fischer-344 rats. A suspension of Walker 256 carcinosarcoma tumour cells (1 x 10(6) cells) was implanted into the right cerebral hemisphere of 8- to 9-week-old rats. Seven days after implantation, the awake rat was infused i.v. for 5 min with 3H-PA (6.4 mCi/kg), 14C-AA (170 microCi/kg) or 14C-DHA (100 microCi/kg). Twenty minutes after the start of infusion, the rat was killed and coronal brain sections were obtained for quantitative autoradiography and histology. Each fatty acid showed well-demarcated incorporation into tumour tissue. Areas of necrosis or haemorrhage showed no or small levels of incorporation. The ratios of incorporation into the tumour to incorporation into contralateral brain regions were 2.8-5.5 for 3H-PA, 2.1-3.3 for 14C-AA and 1.5-2.2 for 14C-DHA. The mean ratios differed significantly between the fatty acids (P < 0.01). 3H-PA was not incorporated into necrotic tumours despite the presence of an open blood-tumour barrier, indicated by extravasated horseradish peroxidase. The incorporation rate constant of 3H-PA was similar for small intracerebral and large extracerebral tumours. The results show that 3H-PA, 14C-AA and 14C-DHA are incorporated more readily into tumour tissue than into brain, and that the increase is primarily due to increased utilization of fatty acids by tumour cells and not due to a high blood-tumour permeability. The relative increases in rates of incorporation for the different fatty acids may be related to lipid composition of the tumour and to the requirement of and specific role of these fatty acids in tumour cell growth and division.

1: J Lipid Res. 2005 Jun;46(6):1278-84. Epub 2005 Mar 16.Click here to read Links
Role of omega-3 polyunsaturated fatty acids on cyclooxygenase-2 metabolism in brain-metastatic melanoma.
Denkins Y, Kempf D, Ferniz M, Nileshwar S, Marchetti D.

Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA. ydenkins@vetmed.lsu.edu

Cyclooxygenase-2 (COX-2) is important in the progression of epithelial tumors. Evidence indicates that omega-6 PUFAs such as arachidonic acid (AA) promote the growth of tumor cells; however, omega-3 fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] inhibit tumor cell proliferation. We investigated the effects of omega-3 PUFA on the expression and function of COX-2 in 70W, a human melanoma cell line that metastasizes to the brain in nude mice. We show that 1) tumor necrosis factor-alpha upregulates the expression of both COX-2 mRNA and prostaglandin E2 (PGE2) production, and 2) omega-3 and omega-6 PUFA regulate COX-2 mRNA expression and PGE2 production. AA increased COX-2 mRNA expression and prostaglandin production in omega-6-stimulated 70W cells. Conversely, COX-2 mRNA expression decreased in cells incubated with EPA or DHA. AA increased Matrigel invasion 2.4-fold, whereas EPA or DHA did not. Additionally, PGE2 increased in vitro invasion 2.5-fold, whereas exposure to PGE3 significantly decreased invasion. Our results demonstrate that incubation of 70W cells with either AA or PGE2 increased invasiveness, whereas incubation with EPA or DHA downregulated both COX-2 mRNA and protein expression, with a subsequent decrease in Matrigel invasion. Taken together, these results indicate that omega-3 PUFA regulate COX-2-mediated invasion in brain-metastatic melanoma.

08-27-2008, 10:14 AM	#11
R.B. Senior Member Join Date: Mar 2006 Posts: 1,843	Beleive51, I hope your 1000th post is better news. I am so sorry to read your news. This sounds so trite but every little helps. Below I copy a trial which suggests there is evidence that brain tumours show a fatty acid imbalance and have a higher fat uptake than normal cells. There is also limited evidence Omega 6 may promote growth and DHA and EPA reduce it through Cox2. Uptake will reflect a combination of dietary and stored fats. So food for thought as to whether it is worth increasing long chain Omega 3s (fish Oil) and reduce omega 6s (primarily the common vegetable oils sunflower, soy, grapeseed etc) which are found in lots of foods. Infusion is a way of getting the DHA EPA to the body more quickly and there have been some trials in cancers. Clearly it is essential to discuss dietary change with your doctors and more so in treatment. They may find the trials thought provoking if nothing else. I am sorry I cannot be more specific but there appears to be only a limited amount of research on the subject. The Greek Diet Thread has much more on the impact of Omega 6 and 3 on BC if you have not already seen it. http://her2support.org/vbulletin/showthread.php?t=24410 RB This is a link to a search on NCBI for brain tumour and DHA. http://www.ncbi.nlm.nih.gov/sites/en...%20tumor%20DHA 1: Lipids. 1996 Dec;31(12):1283-8.Links The fatty acid composition of human gliomas differs from that found in nonmalignant brain tissue. Martin DD, Robbins ME, Spector AA, Wen BC, Hussey DH. Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City 52242, USA. To compare the fatty acid composition of tumor tissue from glioma patients with that of normal brain tissue, tissue samples were obtained from 13 glioma patients and from 3 nonmalignant patients. Following lipid extraction, total fatty acid composition was measured using gas-liquid chromatography. samples were further separated into phospholipids and neutral lipids. Representative samples were then separated into phospholipid classes by thin-layer chromatography and the fatty acid composition assayed. Levels of the polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA), were significantly reduced (P = 0.029) in the glioma samples compared with normal brain samples; mean values were 4.8 +/- 2.9% and 9.2 +/- 1.0%, respectively. This reduction in glioma DHA content was also observed in terms of phospholipids (4.6 +/- 2.1% vs. 9.6 +/- 0.8%, P = 0.002). The phosphatidylserine and phosphatidylethanolamine phospholipid classes were reduced in the glioma samples. Differences were also noted in the n-6 PUFA content between glioma and normal brain samples. The glioma content of the n-6 PUFA linoleic acid was significantly greater (P < 0.05) than that observed in the control samples in terms of total lipids. Thus, the fatty acid composition of human gliomas differs from that found in nonmalignant brain tissue. 1: Clin Exp Metastasis. 1993 Mar;11(2):141-9.Links Intravenously injected radiolabelled fatty acids image brain tumour phospholipids in vivo: differential uptakes of palmitate, arachidonate and docosahexaenoate. Nariai T, Greig NH, DeGeorge JJ, Genka S, Rapoport SI. Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892. This paper investigates the incorporation of intravenously (i.v.) administered radiolabelled fatty acids--[9,10(3)-H]palmitate (3H-PA), [1-14C]arachidonate (14C-AA) and [1-14C]docosahexaenoate (14C-DHA)--into intracerebrally implanted tumours in awake Fischer-344 rats. A suspension of Walker 256 carcinosarcoma tumour cells (1 x 10(6) cells) was implanted into the right cerebral hemisphere of 8- to 9-week-old rats. Seven days after implantation, the awake rat was infused i.v. for 5 min with 3H-PA (6.4 mCi/kg), 14C-AA (170 microCi/kg) or 14C-DHA (100 microCi/kg). Twenty minutes after the start of infusion, the rat was killed and coronal brain sections were obtained for quantitative autoradiography and histology. Each fatty acid showed well-demarcated incorporation into tumour tissue. Areas of necrosis or haemorrhage showed no or small levels of incorporation. The ratios of incorporation into the tumour to incorporation into contralateral brain regions were 2.8-5.5 for 3H-PA, 2.1-3.3 for 14C-AA and 1.5-2.2 for 14C-DHA. The mean ratios differed significantly between the fatty acids (P < 0.01). 3H-PA was not incorporated into necrotic tumours despite the presence of an open blood-tumour barrier, indicated by extravasated horseradish peroxidase. The incorporation rate constant of 3H-PA was similar for small intracerebral and large extracerebral tumours. The results show that 3H-PA, 14C-AA and 14C-DHA are incorporated more readily into tumour tissue than into brain, and that the increase is primarily due to increased utilization of fatty acids by tumour cells and not due to a high blood-tumour permeability. The relative increases in rates of incorporation for the different fatty acids may be related to lipid composition of the tumour and to the requirement of and specific role of these fatty acids in tumour cell growth and division. 1: J Lipid Res. 2005 Jun;46(6):1278-84. Epub 2005 Mar 16.Click here to read Links Role of omega-3 polyunsaturated fatty acids on cyclooxygenase-2 metabolism in brain-metastatic melanoma. Denkins Y, Kempf D, Ferniz M, Nileshwar S, Marchetti D. Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA. ydenkins@vetmed.lsu.edu Cyclooxygenase-2 (COX-2) is important in the progression of epithelial tumors. Evidence indicates that omega-6 PUFAs such as arachidonic acid (AA) promote the growth of tumor cells; however, omega-3 fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] inhibit tumor cell proliferation. We investigated the effects of omega-3 PUFA on the expression and function of COX-2 in 70W, a human melanoma cell line that metastasizes to the brain in nude mice. We show that 1) tumor necrosis factor-alpha upregulates the expression of both COX-2 mRNA and prostaglandin E2 (PGE2) production, and 2) omega-3 and omega-6 PUFA regulate COX-2 mRNA expression and PGE2 production. AA increased COX-2 mRNA expression and prostaglandin production in omega-6-stimulated 70W cells. Conversely, COX-2 mRNA expression decreased in cells incubated with EPA or DHA. AA increased Matrigel invasion 2.4-fold, whereas EPA or DHA did not. Additionally, PGE2 increased in vitro invasion 2.5-fold, whereas exposure to PGE3 significantly decreased invasion. Our results demonstrate that incubation of 70W cells with either AA or PGE2 increased invasiveness, whereas incubation with EPA or DHA downregulated both COX-2 mRNA and protein expression, with a subsequent decrease in Matrigel invasion. Taken together, these results indicate that omega-3 PUFA regulate COX-2-mediated invasion in brain-metastatic melanoma.