Olive oil and Her2 downregulation - question for the propellerheads

[chrisy]

Hi all,

The recent spate of new information and posts on our ever popular olive oil threads brings up a question for me.

The way I am reading this, the active component in olive oil (oleic acid) downregulates Her2 overexpression, or the number of her2 receptors on the cell. It has been shown to be synergistic with Herceptin, which makes sense if part of the action of Herceptin is to inhibit the growth signals by blocking the receptor. It would follow (in my non technical mind) that if oleic acid "downregulates" Her2 by the same mechanism or some other mechanism that reduces the number of available Her2 proteins on the cell, that would be a good thing as it would, like Herceptin, reduce the amount of growth signalling through the Her2.

How am I doing so far?

Now comes my question: Some of our members are in a trial of Herceptin MCC-DM1 (fo shizzah) which is Herceptin with a toxin attached. So it would work by bringing the toxin directly to the cancer cell via the Her2 receptor. In this case, would it be better to have higher overexpression of Her2 so that more of the toxin would reach the cell, and if so, would oleic acid DECREASE the effectiveness of this treatment?

Just when I was about to start dousing my bread in EVOO...

[PinkGirl]

That's an interesting question Chrisy, if I understand it correctly.

Let's say there is a finite number of cancer cells, say 20. Are you
asking if it would be better for each of those 20 cells to have lots
of receptors to better attract the herceptin and toxin and then get zapped?
It makes sense that more receptors would be better. That would
eliminate the olive oil.

It will be interesting to see what the brainiacs come up with.

[hutchibk]

oh jeez - first no vitamin D and now no EVOO... I'm screwed. I feel like my brain is about to melt. LOL

[lilyecuadorian]

waiting for more opinions on this BIG MATTER for me !!!I just drink today 2 spoons of EVOO ...and tomorrow I will get my #5 infusion ...

[RhondaH]

I found this article when I "originally" was not to get Herceptin and wanted to do what I could. In laymans terms, it was found that olive oil (46 % reduction of cell surface) provided "similar" results as Herceptin (48% reduction in cell surface), but TOGETHER they work synergistically (70% reduction in cell surface). SO I would drink up:)

http://www.ncbi.nlm.nih.gov/pubmed/15642702?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVDocSum


RESULTS: Flow cytometric analyses demonstrated a dramatic (up to 46%) reduction of cell surface-associated p185(Her-2/neu) following treatment of the Her-2/neu-overexpressors BT-474 and SK-Br3 with OA. Indeed, this effect was comparable to that found following exposure to optimal concentrations of trastuzumab (up to 48% reduction with 20 microg/ml trastuzumab). Remarkably, the concurrent exposure to OA and suboptimal concentrations of trastuzumab (5 microg/ml) synergistically down-regulated Her-2/neu expression, as determined by flow cytometry (up to 70% reduction), immunoblotting, and immunofluorescence microscopy studies. The nature of the cytotoxic interaction between OA and trastuzumab revealed a strong synergism, as assessed by MTT-based cell viability and anchorage-independent soft-agar colony formation assays.


Rhonda

[Mary Jo]

Hi Rhonda,
I read that too and it sure excited me. Makes the grossness of "drinking" it seem worth it. http://www.her2support.org/vbulletin/images/icons/icon7.gif

Hugs,
Mary Jo

[RobinP]

Chrisy, I think your question alone demonstrates that you are perhaps a propellarhead yourself. I think you know the answer to your question too. I want to confirm what your concerns are via the posted article that Rhonda so kindly posted above. The p185 surface area was reduced following tx. with OA. Now, Herceptin also decreases the p185 surface area receptor site. When Herceptin and OA are given together, there is according to this article a synergistic reaction where both work to decrease the receptor site of p185, thus decreasing heterodimerzation with other deleterious her family members, such as her1 and her3. As the p185 receptor site is blocked with the help of herceptin and OA, phosphorlazation and the downward PI3K pathway is block to prevent cellular proliferation. As you can see H. and OA are working together to prevent cellular replication. However, in your trail, you are counting on the Herceptin and cytoxic agent to destroy the her2 molecule, not prevent it from replication as the study Rhonda posted. Therefore, you need all the Herceptin and cytoxic agent you can get into the p185 site in order to destroy THE HER2 MOLECULE. NO, YOU DO NOT WANT OA, IN THIS CASE, TO COMPETE WITH THE P185 RECEPTOR SITE. YOU WANT ALL THE CYTOXIC AGENT CARRIED BY HERCEPTIN INTO THAT HER2 SITE WITHOUT THE COMPETING OA, OA DOES NOT CARRY THE CYTOXIC AGENT. I WOULD DEFINATELY CUT OUT ALL OA IN YOUR DIET. IN FACT, I AM SURPRISED THAT THE TRAIL DOES NOT SPECIFY OA RESTRICTION. I WOULD WRITE A LETTER TO THE INVESTIGATORS ABOUT YOUR CONCERNS OVER OA.

RESULTS: Flow cytometric analyses demonstrated a dramatic (up to 46%) reduction of cell surface-associated p185(Her-2/neu) following treatment of the Her-2/neu-overexpressors BT-474 and SK-Br3 with OA. Indeed, this effect was comparable to that found following exposure to optimal concentrations of trastuzumab (up to 48% reduction with 20 microg/ml trastuzumab). Remarkably, the concurrent exposure to OA and suboptimal concentrations of trastuzumab (5 microg/ml) synergistically down-regulated Her-2/neu expression, as determined by flow cytometry (up to 70% reduction), immunoblotting, and immunofluorescence microscopy studies. The nature of the cytotoxic interaction between OA and trastuzumab revealed a strong synergism, as assessed by MTT-based cell viability and anchorage-independent soft-agar colony formation assays.

[chrisy]

Robin,
You restated my concerns EXACTLY, only it sounded much more impressive and scientific! At best, I'm an illiterate propellerhead! Maybe we can go into business together translating this stuff between "english" and "science".

You come to the same opinion I did, and I will definitely pose this question.

Lily - let me know what you find out on your end, it's an interesting question, isn't it? On the other hand, you are clearly doing very well on this drug, so by the "proof is in the pudding" standard it seems not to be hurting.

Brenda, I think you should be ok on the EVOO since for you reducing the amount of Her2 would still be a good thing. In fact, you could probably have my share, too! Ever chug a bottle of EVOO???

If I were to predict, I would guess that the doc's answer will be to avoid ingesting excessive amounts of oleic acid. But unfortunately I doubt the recommendation will be to go back to eating butter!

Hoping to hear some more people weigh in on this...

[Lolly]

This is an interesting thread. I've been wondering about this myself, only didn't quite know how to form the question coherently, so thanks Chris for bringing it up, it's really "food for thought".

<3 Lolly

[chrisy]

On the other hand... these articles suggeststhat something in EVOO reverses herceptin resistance by reducing the cleavage of the Her2 extracellular domain which as I read it, would present more receptors for the herceptin to bind to.

We are certainly complicated creations, aren't we?? I definitely need some expert help in interpreting this stuff.

Maybe I can get Dr. Menendez to accompany me to my appointment. Of course, I think he's in Spain now, so that might be a problem.

http://www.ncbi.nlm.nih.gov/pubmed/16632435?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVDocSum

http://www.ncbi.nlm.nih.gov/pubmed/17490486?ordinalpos=7&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVDocSum

[RobinP]

Chrisy, you did introduce a very interesting and good question, which is very technical and difficult to answer. I just want to further clarify this topic... doesn't olive oil reduce the number of her2 docking sites where herceptin would bind, not increase it? Because according to one of the articles you posted above, " oleuropein aglycone ( olive oil) treatment significantly reduced (note not increase!) HER2 ECD cleavage OR HERCEPTIN DOCKING SITES and subsequent HER2 auto-phosphorylation. " Wow, I am certainly not an expert, but Iam trying to help.I surely hope you can reach the researchers and clarify some of your pertinent questions and whether taking olive oil will effect your trail. I wish you the very best of luck and hope the new trail Herceptin you are trying will be very effective and completely successful! You deserve the very best. Take care. Please continue to post and let us know how you are doing in your trail. Praying for you.

[TSund]

Just plugging into this interesting conversation. Thanks for letting me follow along! :)

Side question: IF EVOO can make this dramatic synergy with Herceptin, WHY aren't oncologists standardly prescribing it alongside Herceptin? (outside of the dynamics in this thread) Seems like it only makes sense?!

Thanks

Terri

[chrisy]

Robin,
As you can tell, I'm not a science person either, but I interpreted the second article as it decreased the cleavage (that is to say, the discarding of the extracellular "docking station") so to me that would present more receptors.

Really need some help from people who understand this stuff! I didn't get to see the doctor yesterday but will start there with these studies.

I think EVOO (as well as other nutritional interventions) are not prescribed is that the data is not compelling enough - there is evidence, but not "proof" that this effect is seen in humans. All these studies were in the petri dish I think. But I think human studies may be underway which is good, we definitely need answers. Joe posted I think in "articles of interest" a link to MD Anderson's complementary website evaluating this stuff. It was really good, but in terms of grades, most things were not conclusive and got a "C".

[TSund]

Thanks, Chrisy!

So, the studies were inconclusive because the evidence was inconclusive, or because there's just not been the "real people" studies to prove it one way or another? This drives me nuts. Kajillions of dollars spent to try to prove expensive drugs, but we can't get our act together to show what nutrients will help and which will hurt for certain.

[Becky]

Agreed, agreed with Terri and others. Although foods and/or supplements are powerful medicines (or in the case of McDonalds - poisons), they have not been part of any clinical trials therefore much remains to be totally proven. And doctors don't recommend or try anything without a proven trial - hence some situations many of us have been in during this journey.

However, there are some bonefide facts - a healthful diet is healthy. When I was on Herceptin therapy, if I didn't have a salad everyday that I made a dressing with extra virgin olive oil, I would take a tablespoon off a spoon. I was at my sister's once and my niece saw me do this. She immediately told my sister who told my niece - its one of those things Aunt Becky does. If she believes it helps her then it does.

[Lolly]

Another good way to get your daily dose of EVOO (at least I like it this way :) ) is, if you like hot cereal in the morning, instead of butter add a tblsp. of EVOO. It tastes pretty good on oatmeal, along with a little brown sugar and soy milk!

<3 Lolly

[R.B.]

Tsund.

Re your observation.

Who will / funds trials that involve risk reduction through lifestyle and diet?

And why ?

[TSund]

R.B.,

Yes, that is the crux, isn't it?

TRS

[R.B.]

Tsund

<img src="http://img65.imageshack.us/img65/8338/2cents3fo.gif" alt="2 Cents" />

<img src="http://img52.exs.cx/img52/4566/i7pfrusty.gif" alt="Hitting Head Against Wall" />

YES !

<img src="http://forum.crystalxp.net/style_emoticons/default/bigboulay.gif" alt="Ball and Chain (Large)" />

[TSund]

Our onc did this interview, I do not know how old it is:

http://www2.healthtalk.com/go/cancer/breast-cancer/webcasts/chemo-after-breast-cancer-surgery-the-state-of-the-art/transcripts/low-fat-diet-shown-to-keep-breast-cancer-from-coming-back

[Carol Carlson]

I consider myself to be a fairly intelligent person. However, I am totally confused and baffled by Rhonda's post.
Robin seems to have some good solid questions.
"Out in left field"
Carol

[Barbara2]

I looked for a date, too, but didn't see one. I'm sure that advice still stands strong for reduction of breast cancer return. It was a good interview. Thanks!

[RobinP]

Dear Chrisy,

I'm not a Duke University medical researcher or professor. Nor am I a Glasco-Smith-Kline researcher, who was the lead investigativor of Lapatinib research and her2 pathways. However, Dr. Neil Spector is/was both and I have spoken to him about the her2 pathways and dimerazation of the ECD. I contacted him in 2005 after I listened to him lecture on the SABC website about her2 pathways and I asked him about the efficacy of late Herceptin verses Laptinib and he kindly gave his opinion and rationale for late Herceptin. While we spoke,he said that I had a better knowledge base than most oncologists that he had spoken to concerning the her2 pathway. If that is true, maybe my opinion has value. Again, I tend think that the ECD would be decreased by olive oil and would compete with the toxic Herceptin agent(DM1), making the toxic Herceptin agent less effective if THERE ARE OPTIMAL QUANTITIES OF DMI AVAILABLE. IF THERE ARE OPTIMAL QUANTITIES OF THE TOXIC MONOCLONAL ANTIBODY, DMI, THEN THERE WOULD BE ENOUGH ANTIBODIES TO BIND AND HETERODIMERIZE WITH ALL OF THE AVAILABLE HER2 RECEPTORS, THEORECTICALLY MAKING DM1 TOTALLY EFFECTIVE IN OF AND OF ITSELF. IF YOU ARE NOT GETTING ENOUGH DMI,THEN IT APPEARS THAT OLIVE OIL CAN ASSIST WITH THE LACK OF DMI AND THUS BIND WITH THE REMAINING HER2 SITES, BUT IT WOULD NOT KILL OR BE CYTOXIC AT THESE SITES LIKE DMI, CYTOXIC HERCEPTIN. IN THE CASE WHERE THERE ARE SUBOPTIMAL QUANTITIES OF HERCEPTIN-DMI, OLIVE OIL WOULD ASSIST IN BINDING THE REMAINING HER2 RECEPTOR SITES AND THUS ACT IN SYNERGY WITH HERCEPTIN-DMI. ALL THIS IS THEORETICAL, AS TSUND SUGGESTS, AND IT IS TRUE THAT ONLY A CLINICAL TRAIL, EITHER IN VITRO AND VIVO WOULD GIVE US MORE ANSWERS.


PS Please see Neil Spector's webcast on the her2 pathways at the SABC website from 2005 to understand more on the her2 pathway. Also, see the CURE magazine past issues and look for articles on her2, which are descriptive on heterdimerzation and her2.
BEST OF LUCK AND HOPING THE BEST FOR YOU AND DON'T BE AFRAID TO WRITE OR CALL SOME OF THE RESEARCHERS ON YOUR TRAIL OR THOSE EXPERT HER2 PATHWAY RESEARCHERS WHO MAY BE ABLE TO HELP.

HOPEFULLY HELPFUL, ROBIN

[TSund]

Robin,

Does it come down to which might do the "greater good" then?

I too am impressed with your knowledge and understanding. Please weigh in on the other issues floating around... :) (an aside: any take on the progesterone question?)

Terri