HER2 Support Group Forums - View Single Post - The traditional diet of Greece and cancer.

R.B. · 10-03-2012, 04:42 PM

Lani kindly posted this comment / paper summary which identifies COX1 and COX2 related genes as possible targets in HER2 related cancer. Interestingly COX 1 and COX 2 are key enzymes in the Omega 6 pathways in that they convert Omega 6 fats to active derivatives. NSAIDS intervene in these pathways in different ways and prevent formation of these products. . . In very simplistic terms reducing the amount of plant based Omega 6 in the diet to under 4% of calories and increasing Omega 3 which competes for space in the cell membrane will also reduce the amount of Omega 6 COX products made by the body.

The full free version of the paper referred to in the above post includes the following comment. "In animal studies, omega-6 PUFAs have a strong mammary tumor-enhancing effect [21,22]. In order to exert their carcinogenic effects, they must first undergo an oxidative metabolization, mainly through the lipoxygenase and cyclooxygenase pathways [23,24]. " COX is the short form for cyclooxygenase, the same COX 1 and COX 2 family as Lani is talking about above. COX enzymes prefer Omega 6s. So give COX enzymes a ready supply of Omega 6 and the right conditions and they will get busy. Incidentally LOX enzymes prefer Omega 3s, but will also use Omega 6s particularly when Omega 3s are in short supply . . .

http://her2support.org/vbulletin/showthread.php?t=56001

"I have railed for years on the need to divide her2+ bc into subtypes in order to discover the best targets/ combination treatment for each subtype

I have also railed for years to encourage bone marrow sampling to discover if the disseminated tumor cells there could tell which patients needed systemic therapy as well as local treatment (surgery and/or radiation therapy) and to discover whether the initial therapy was successful or whether additional therapy against other targets is needed

I have not hidden that I believe in the cancer stem cell "theory" of breast cancer

Here scientists have found (in mice, but results corroborated when evaluating a cohort of human breast cancer patients accumulated by vantViver) that an 8 gene signature derived from cancer stem cells of her2+ breast cancer (in mice)
can stratify her2+ breast cancer patients prognoses and serve as targets for therapy.

Two of the genes can be affected by over the counter NSAIDs (cox1 and cox2) and an already FDA approved drug in use for many years -an iron chelator used for iron poisoning and inherited iron deposition diseases is available as well.

I am hopeful studies in this direction will help stratify her2+ breast cancer into groups (even though every patients tumor is unique) which can be treated similarly ie similar targets, turning her2+ breast cancer into an annoying chronic disease or even curing it.

I hope this approach can be used against other forms of cancer as well

Proteomics. 2012 Sep 19. doi: 10.1002/pmic.201200103. [Epub ahead of print]
Proteomic profiling of cancer stem cells derived from primary tumors of HER2/Neu transgenic mice.
Kanojia D, Zhou W, Zhang J, Jie C, Lo PK, Wang Q, Chen H.
Source
Department of Biological Science, Centre for colon cancer, University of South Carolina, Columbia, SC 29208, USA.
Abstract
HER2 overexpression leads to mammary tumorigenesis and its elevated levels leads to increase in cancer stem cells (CSCs), invasion and metastasis. CSCs are resistant to radiation/chemotherapeutic drugs and are believed to be responsible for recurrence/relapse of cancer. CSCs are isolated using flow cytometry based sorting, although reliable, this technology hinders the convenient identification of molecular targets of CSCs. Therefore to understand the molecular players of increased CSC through HER2 overexpression and to develop meaningful targets for combination therapy, we isolated and characterized breast CSCs through convenient tumorsphere culture. We identified the altered protein expression in CSC as compared to non-CSC using LC-MS/MS and confirmed those results using qRT-PCR and western blotting. Ferittin Heavy Chain 1 was identified as a candidate gene which is involved in iron metabolism and iron depletion significantly decreased the self-renewal of CSCs. We further performed in silico analysis of altered genes in tumorsphere and identified a set of genes (PTMA, S100A4, S100A6, TNXRD1, COX-1, COX-2, KRT14 and FTH1), representing possible molecular targets, which in combination showed a promise to be used as prognostic markers for breast cancer.
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PMID: 22997041"

10-03-2012, 04:42 PM	#385
R.B. Senior Member Join Date: Mar 2006 Posts: 1,843	Re: The traditional diet of Greece and cancer. Lani kindly posted this comment / paper summary which identifies COX1 and COX2 related genes as possible targets in HER2 related cancer. Interestingly COX 1 and COX 2 are key enzymes in the Omega 6 pathways in that they convert Omega 6 fats to active derivatives. NSAIDS intervene in these pathways in different ways and prevent formation of these products. . . In very simplistic terms reducing the amount of plant based Omega 6 in the diet to under 4% of calories and increasing Omega 3 which competes for space in the cell membrane will also reduce the amount of Omega 6 COX products made by the body. The full free version of the paper referred to in the above post includes the following comment. "In animal studies, omega-6 PUFAs have a strong mammary tumor-enhancing effect [21,22]. In order to exert their carcinogenic effects, they must first undergo an oxidative metabolization, mainly through the lipoxygenase and cyclooxygenase pathways [23,24]. " COX is the short form for cyclooxygenase, the same COX 1 and COX 2 family as Lani is talking about above. COX enzymes prefer Omega 6s. So give COX enzymes a ready supply of Omega 6 and the right conditions and they will get busy. Incidentally LOX enzymes prefer Omega 3s, but will also use Omega 6s particularly when Omega 3s are in short supply . . . http://her2support.org/vbulletin/showthread.php?t=56001 "I have railed for years on the need to divide her2+ bc into subtypes in order to discover the best targets/ combination treatment for each subtype I have also railed for years to encourage bone marrow sampling to discover if the disseminated tumor cells there could tell which patients needed systemic therapy as well as local treatment (surgery and/or radiation therapy) and to discover whether the initial therapy was successful or whether additional therapy against other targets is needed I have not hidden that I believe in the cancer stem cell "theory" of breast cancer Here scientists have found (in mice, but results corroborated when evaluating a cohort of human breast cancer patients accumulated by vantViver) that an 8 gene signature derived from cancer stem cells of her2+ breast cancer (in mice) can stratify her2+ breast cancer patients prognoses and serve as targets for therapy. Two of the genes can be affected by over the counter NSAIDs (cox1 and cox2) and an already FDA approved drug in use for many years -an iron chelator used for iron poisoning and inherited iron deposition diseases is available as well. I am hopeful studies in this direction will help stratify her2+ breast cancer into groups (even though every patients tumor is unique) which can be treated similarly ie similar targets, turning her2+ breast cancer into an annoying chronic disease or even curing it. I hope this approach can be used against other forms of cancer as well Proteomics. 2012 Sep 19. doi: 10.1002/pmic.201200103. [Epub ahead of print] Proteomic profiling of cancer stem cells derived from primary tumors of HER2/Neu transgenic mice. Kanojia D, Zhou W, Zhang J, Jie C, Lo PK, Wang Q, Chen H. Source Department of Biological Science, Centre for colon cancer, University of South Carolina, Columbia, SC 29208, USA. Abstract HER2 overexpression leads to mammary tumorigenesis and its elevated levels leads to increase in cancer stem cells (CSCs), invasion and metastasis. CSCs are resistant to radiation/chemotherapeutic drugs and are believed to be responsible for recurrence/relapse of cancer. CSCs are isolated using flow cytometry based sorting, although reliable, this technology hinders the convenient identification of molecular targets of CSCs. Therefore to understand the molecular players of increased CSC through HER2 overexpression and to develop meaningful targets for combination therapy, we isolated and characterized breast CSCs through convenient tumorsphere culture. We identified the altered protein expression in CSC as compared to non-CSC using LC-MS/MS and confirmed those results using qRT-PCR and western blotting. Ferittin Heavy Chain 1 was identified as a candidate gene which is involved in iron metabolism and iron depletion significantly decreased the self-renewal of CSCs. We further performed in silico analysis of altered genes in tumorsphere and identified a set of genes (PTMA, S100A4, S100A6, TNXRD1, COX-1, COX-2, KRT14 and FTH1), representing possible molecular targets, which in combination showed a promise to be used as prognostic markers for breast cancer. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. PMID: 22997041" Last edited by R.B.; 10-03-2012 at 05:07 PM..