~Mighty Oak's Brain Results~10-30-2008

[Sherryg683]

There's no reason to believe that if it worked for the others, it won't work for this one. I know you just hate to see him have to go through all this again. How is he holding up mentally, he has been through so much, you have been his rock through all this...sherryg683

[sassy]

Marie,

Please know that you are in all our thoughts and prayers. What works on 10 should work fine on one. Just another pesky step.

[Lani]

excellent combination herceptin and lapatinib may be lifts your spirits:


Home > Abstracts & Virtual Meeting > Abstracts > 2008 ASCO Annual Meeting

Effect of lapatinib on accumulation of inactive HER2 at the cell membrane and on antibody-dependent cellular cytotoxicity (ADCC) mediated by trastuzumab: A novel mechanism for the enhanced effects of combined anti-HER2 therapy.
Sub-category:
Tyrosine Kinase Inhibitors
Category:
Developmental Therapeutics: Molecular Therapeutics
Meeting:
2008 ASCO Annual Meeting
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Abstract No:
3594
Citation:
J Clin Oncol 26: 2008 (May 20 suppl; abstr 3594)
Author(s):
M. Scaltriti, C. Verma, M. Guzman, J. Jimenez, J. Parra, K. Pedersen, S. Landolfi, S. Ramon y Cajal, J. Arribas, J. Baselga
Abstract:
Background: Lapatinib is a HER2 tyrosine kinase inhibitor that has clinical activity in HER2 overexpressing (HER2+) breast cancer. In vitro and clinical studies have shown that lapatinib enhances the effects of the monoclonal antibody trastuzumab suggesting partially non-overlapping mechanisms of action. In order to dissect the differential mechanims of these agents, we have studied the effects of lapatinib and trastuzumab on receptor expression and signaling and have explored a new potential mechanism underlying the profound antitumor activity of the combination. Methods: HER2+ breast cancer cells SKBR3 and MCF7-HER2 were treated with lapatinib, trastuzumab or both. Assays of receptor expression, phosphorylation, signalling and tumor growth were performed. Trastuzumab-dependent cellular cytotoxicity was measured with different levels of HER2 expression and doses of lapatinib. Results: Lapatinib treatment of HER2+ breast cancer cells inhibited HER2 phosphorylation, prevented ubiquitination and resulted in a marked accumulation of inactive receptors at the cell surface. By contrast, trastuzumab caused enhanced HER2 phosphorylation, ubiquitination and degradation of the receptor. By immunoprecipitation and computational protein modelling techniques we further demonstrated that the lapatinib-induced accumulation of HER2 lead to stabilization of inactive HER2 homo- and hetero-dimers. Accumulation of HER2 induced by lapatinib and downregulation of HER2 mediated by trastuzumab were also observed in vivo, where the combination of the two agents triggered complete tumor remission in all cases after 10 days of treatment. Lapatinib-induced accumulation of HER2 at the cell surface markedly enhanced trastuzumab-mediated ADCC. Conclusions: Lapatinib results in a marked accumulation of inactive HER2 receptors at the cell surface both in vitro and in vivo. This increase in receptors number at the cell surface enhances ADCC by trastuzumab. We propose that this is a novel mechanism that may be clinically relevant and exploitable in the therapy of patients with HER2+ tumors.

[SoCalGal]

Oh Marie - I will send some prayers to you and Ed. xo Flori

[naturaleigh]

Marie,

The GK did its job last time and it will do it again!! This time should not be as stressful since he now knows what to expect. Many times the not knowing is more stressful than the actual procedure.

I hope his back starts feeling better soon too.

You will get through this bump in the road and before you know it, you will be cruising those open water again.

Lots of love and hugs to you both!!

[Chelee]

Oh my goodness Marie...I am so sorry to hear about the recent news. But it sure sounds like Ed has a really good team of doctors so I am sure they will have a good plan of action.

I will be praying for Ed that they blast this last met into the twilight zone and you two can have some peace. May God bless you both and give you the strength you need to get this all behind you. I will keep you both in my thoughts and prayers. Hang in there. Sending you a really big cyber hug!

Chelee

[Patb]

God bless you and Ed both and I will pray for extra
energy and strength to guide you through the next
treatment.
patb

[juanita]

sending lots of hugs and prayers your way!

[Jackie07]

Marie,

You are an amazing woman. Please know that we are all behind you. Ed is so lucky to have a spouse like you to back him up.

Sending prayers from Central Texas.

[duga35]

God bless you both....
I know this has been such a battle for the both of you and my prayers are with you.
Please tell Ed that I feel very strongly that he will beat this horrible affliction.

[Believe51]

One of two problems has escalated here; ONE being the brain met and TWO being the cervical spine which was something we have always watched. This suspicious area has bone marrow issues which could be simply bone mets to this spot. Although we are unsure of a secondary cancer at this time. Further testing needs to be done here, so we are getting orders written.

Friday evening close to 9pm our Oncologist called to check up on us. Our attack will be planned today and we already know what this needs to be. The important part is if the Gamma Knife doctor feels he can wait a couple of weeks to see if more mets declare themselves. Our Oncologist is going to wait for them answers for this puzzle. He feels that the cervical spine is not the issue the other radiologists may think they see without these scans (but who knows for sure?). This could be part of the ongoing saga in Ed's bones and maybe this is where the reoccurrence is happening.

So, Monday (today) is the day I call the Gamma Surgeon to see if we can wait atleast 2-3 weeks...Uggh! The call to our Oncologist will contain the appointment day for GammaMan and his orders. I will then have appointments with OncMan and his orders. These will all blend into communications with teams and by Wednesday we will aggressively put plans to work.

And for all of you here praying and a-wishing for our future.....We have planned another cruise for September 26th, 2009. Gorgeous room with extended balcony headed back to St. Thomas and includes St. Marteen and Nassau. I am all done looking forward to only test results, there has to be more to our lives, there has to be more reasons! Onward and forward. Hopefully though, we can leave the Decadron home.....LOL!

Love to all, thanks for your loving support>>Believe51

[Mary Anne in TX]

You know, Marie, recently I've decided that it might be a better life just continuing to live "as if" in the "life-is-good-I-own-the-world" world! Had a dream the other night...you raced through it in your giant, early-80's, decked out convertible cadillac! Hair blowing, Ed laughing, and beautiful blue skies! Great moment!
I'll keep praying and you keep on believin'. ma

[Bill]

Hi sweet Marie. I'm sorry to hear this about Ed's new met. However, it is good that the Gamma knifing worked so well on the others. I'm sorry if I've missed anything. I just got back, but you guys have been in my thoughts and prayers. You know, Marie, that this is just another battle/test in the war. You guys can do this!

[jones7676]

Thinking of you and praying for the best for you.