Induction of the differentiation and apoptosis of tumor cells in vivo with efficiency and selectivity.

Eur J Dermatol. 2004 Mar-Apr;14(2):96-102.

Tabs S, Avci O.

Yasemin Sokak No. 6, Narlidere, Izmin 35320, Turkey. sinantas1@yahoo.com

Hedgehog/smoothened signaling is active in a variety of tumors and is also involved in the maintenance of normal stem cells in vivo. We evaluated the possibility of preferential affection of tumor versus normal cells following inhibition of this signaling. We applied a cream preparation of cyclopamine (an inhibitor of the hedgehog/smoothened signaling) onto skin tumors in patients who were scheduled for the excision of these tumors (four basal cell carcinomas and a trichoepithelioma in four unrelated patients). All of the cyclopamine-treated tumors regressed rapidly. Histological and immunohistochemical analyses showed inhibition of the proliferation and highly efficient induction of the differentiation and apoptosis of tumor cells by a non-genotoxic mechanism. No adverse effects were noted and normal skin tissue and putative stem cells that were exposed to cyclopamine together with tumors were well preserved under the conditions we describe. Our findings show selective and highly efficient induction of the differentiation and apoptosis of tumor cells in vivo by transient inhibition of the hedgehog/ smoothened signaling and provide a rational cancer therapy. Copyright John Libbey Eurotext 2003.

here is a pic from that study



http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15196999&query_hl=1

Dermatology. 2004;209(2):126-31.

Rapid clearance of psoriatic skin lesions induced by topical cyclopamine. A preliminary proof of concept study.

Tas S, Avci O.

Yasemin Sokak No. 6, Narlidere, Manavkuyu Mahallesi 244 Sokak, 5-1/2 Bornova, Izmir, Turke

BACKGROUND: We have earlier found a highly efficient induction of the differentiation of epidermal lineage skin tumors by cyclopamine, a steroidal alkaloid inhibitor of the hedgehog/smoothened signaling, under conditions in which cyclopamine exerted no adverse effect on skin. OBJECTIVE: We aimed to develop a mechanism-based treatment for psoriasis with cyclopamine. METHODS: We subjected psoriatic skin lesions to cyclopamine under conditions similar to those we used for skin tumors and evaluated the responses of lesions clinically and by histopathological/immunohistochemical analyses. RESULTS: All treated lesions in different patients having plaque and guttate forms of psoriasis regressed rapidly. Differentiation of the epidermal cells of lesional skin and disappearances of infiltrating inflammatory cells were evident within a day. Lesions were cleared commonly on days 3-4. Former treatment sites followed up for more than 24 months now show a lack of adverse effects in the long term. CONCLUSION: An effective treatment for psoriasis is described, consistent with intervention in a proximal/key pathogenic event.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15316166&query_hl=8

While they have not filed for psoriasis, it shows that there might be little to no adverse side effects with a Hh antagonist.

Penetration:

How could some researchers in europe get it to work but DNA couldn't ...

Seems like that should have been the easy part ....

GEEZ , DAN....

I will tell you the only good thing. Dan and company like to cash in stock in the 5$ range for bonus time... and I have no idea how they are going to do it this time.