Any new developments on: sorafenib

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Any new developments on: sorafenib

Postby vandy » Tue Mar 27, 2012 1:41 pm

Does anyone have any new developments on the use of this drug?

Non-surgical Way to Treat Brain Cavernoma?

Read the article online at:

http://www.ecoworld.com/other/non-surgical-way-treat-brain-cavernoma.html

Henk :ugeek:

other link:

http://en.wikipedia.org/wiki/Sorafenib
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Re: Any new developments on: sorafenib

Postby socalsue » Wed Mar 28, 2012 6:44 pm

There's something about this that doesn't seem quite right to me. I didn't see a reference to the original paper but it you find one, in English, pass it on to me.

It sounds to me more likely they may be talking about AV malformations, which, I think, are more dynamic on a cellular basis. Perhaps a translation problem? (study was done in Germany) Most CA drugs work by targeting fast growing cells. Cancer cells grow really fast, thus making them vulnerable to these drugs. Unfortunately, many normal cells are also fast growing, thus leading to the horrific side effects from many CA drugs.
I'm an MD in practice for 26 years. Found out I had a CM in Feb. 2012 after 2 years of TLE from a bleed. Epileptic symptoms were subtle and psychiatric, which is why I let them go on for so long before I saw a neurologist.

I hope I can use my medical knowledge to help out here. . . just remember, I'm not your doctor, and I messed up when I acted as my own doctor.
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Re: Any new developments on: sorafenib

Postby vandy » Wed Mar 28, 2012 6:49 pm

Have a look at this citation:

Schleider E, Stahl S, Wüstehube J, Walter U, Fischer A, Felbor U. Evidence for anti-angiogenic and pro-survival functions of the cerebral cavernous malformation protein 3. Neurogenetics 2010; Sep 23. [Epub ahead of print].

If you can find the article great. I will look as well.

Henk :ugeek:

ps It was mention on this web site as well.

read : http://www.angiomacommunity.org/blog/2010/08/the-search-for-medications-to-treat-cavernous-angioma/
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Re: Any new developments on: sorafenib

Postby josh » Wed Mar 28, 2012 6:54 pm

I think this is the original paper from 2010:

http://www.ncbi.nlm.nih.gov/pmc/article ... ool=pubmed

Cerebral cavernous malformation protein CCM1 inhibits sprouting angiogenesis by activating DELTA-NOTCH signaling

Joycelyn Wüstehube,ab1 Arne Bartol,ab1 Sven S. Liebler,ab René Brütsch,a Yuan Zhu,c Ute Felbor,d Ulrich Sure,c Hellmut G. Augustin,ab and Andreas Fischerab2
Diagnosed at age 35 after brainstem hemorrhage in December 2010."1.0 x 0.4 x 0.9 cm focal lesion in the anterior aspect of the medulla most consistent with cavernous angioma." MRI in March 2012 shows growth and symptoms worsening (sigh). MRI in Sep 2012 maybe shrinking! New bleed in 2014,CM bigger,recovering OK *meh*
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Re: Any new developments on: sorafenib

Postby josh » Wed Mar 28, 2012 6:56 pm

josh wrote:I think this is the original paper from 2010:

http://www.ncbi.nlm.nih.gov/pmc/article ... ool=pubmed

Cerebral cavernous malformation protein CCM1 inhibits sprouting angiogenesis by activating DELTA-NOTCH signaling

Joycelyn Wüstehube,ab1 Arne Bartol,ab1 Sven S. Liebler,ab René Brütsch,a Yuan Zhu,c Ute Felbor,d Ulrich Sure,c Hellmut G. Augustin,ab and Andreas Fischerab2


BTW the abstract is fairly dense, I think the punchline is:

"In this setting, the multikinase inhibitor Sorafenib can ameliorate loss of CCM1-induced excessive microvascular growth, reducing the microvessel density to levels of normal wild-type endothelial cells."
Diagnosed at age 35 after brainstem hemorrhage in December 2010."1.0 x 0.4 x 0.9 cm focal lesion in the anterior aspect of the medulla most consistent with cavernous angioma." MRI in March 2012 shows growth and symptoms worsening (sigh). MRI in Sep 2012 maybe shrinking! New bleed in 2014,CM bigger,recovering OK *meh*
----
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Re: Any new developments on: sorafenib

Postby vandy » Wed Mar 28, 2012 6:58 pm

Thanks Josh.

BTW - no correlating articles? Thanks.

Henk :ugeek:
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Re: Any new developments on: sorafenib

Postby socalsue » Wed Mar 28, 2012 11:11 pm

"Dense" is an understatement! That does seem to be the correct link for the article. I actually read the whole thing and think I get the jist of it.

This was a very, very basic type of research which explored the pathogenesis of CCM's on a molecular level. The fact that anyone is even doing this level of hard science on this illness is amazing and impressive. Go Germany!

They created a good mouse model for CCM (that alone could have been the subject of one paper.) Then they tried out a controlled study of this cancer drug to see the effect. The drug prevented the formation of CCM types of vessels and the control group did develop them.

One key point here is that it "prevented the formation" as opposed to shrinking existing CCM's. Assuming this drug can do this in people, I'm guessing it would benefit people with the inherited form the most.

I think the main thing and the AWESOME thing is that they developed a great animal model for future research. They basically spliced the human gene onto the mice so they have the human problem. They can put these cells in the mice where they want them.

This is why I don't like PETA. I'm ok with sacrificing mice for the sake of people.
I'm an MD in practice for 26 years. Found out I had a CM in Feb. 2012 after 2 years of TLE from a bleed. Epileptic symptoms were subtle and psychiatric, which is why I let them go on for so long before I saw a neurologist.

I hope I can use my medical knowledge to help out here. . . just remember, I'm not your doctor, and I messed up when I acted as my own doctor.
socalsue
 
Posts: 39
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Location: Southern California

Re: Any new developments on: sorafenib

Postby josh » Thu Mar 29, 2012 5:42 pm

vandy wrote:Thanks Josh.

BTW - no correlating articles? Thanks.

Henk :ugeek:


Not exactly a related article but Joycelyn Wüstehube ended up working on this 2010 paper also about CCM3 expression:

http://www.ncbi.nlm.nih.gov/pmc/article ... ool=pubmed
Diagnosed at age 35 after brainstem hemorrhage in December 2010."1.0 x 0.4 x 0.9 cm focal lesion in the anterior aspect of the medulla most consistent with cavernous angioma." MRI in March 2012 shows growth and symptoms worsening (sigh). MRI in Sep 2012 maybe shrinking! New bleed in 2014,CM bigger,recovering OK *meh*
----
The Chronicles of a Rebel Brain http://brainrebel.blogspot.com/
josh
 
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Re: Any new developments on: sorafenib

Postby josh » Thu Mar 29, 2012 5:49 pm

Nice meta-analysis socalsue!

Too bad we had not heard more about sorafenib. Anything to help control these angiomas! But it seemed that costs may have steered the research elsewhere, maybe that is why we have not heard much about it.

http://www.angiomacommunity.org/blog/20 ... s-angioma/
"A downside of sorafenib is its price; for example, it has been disallowed for use as a treatment for liver cancer by the United Kingdom National Health Service because treatment can cost more than $4500 USD/month. The identification of sorafenib, however, has opened the door to a different class of medications that can be explored. "
Diagnosed at age 35 after brainstem hemorrhage in December 2010."1.0 x 0.4 x 0.9 cm focal lesion in the anterior aspect of the medulla most consistent with cavernous angioma." MRI in March 2012 shows growth and symptoms worsening (sigh). MRI in Sep 2012 maybe shrinking! New bleed in 2014,CM bigger,recovering OK *meh*
----
The Chronicles of a Rebel Brain http://brainrebel.blogspot.com/
josh
 
Posts: 83
Joined: Wed Mar 14, 2012 7:23 am
Location: San Jose, CA


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