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Biotech / Medical : Ligand (LGND) Breakout! -- Ignore unavailable to you. Want to Upgrade?

To: Zeuspaul who wrote (15296)	2/19/1998 7:31:00 AM
From: Henry Niman	Read Replies (1) \| Respond to of 32384

Zeuspaul, Speaking of credibility, look at the current issue of Nature. LGND exclusive consultant, scientific founder, and head of Scientific Advisory Board, Ron Evans, has a major paper on a cofactor that influences the action of retinoids as will as factors that will modulate this activity: Role of the histone deacetylase complex in acute promyelocytic leukaemia Non-liganded retinoic acid receptors (RARs) repress transcription of target genes by recruiting the histone deacetylase complex through a class of silencing mediators termed SMRT or N-CoR. Mutant forms of RAR-alpha, created by chromosomal translocations with either the PML (for promyelocytic leukaemia) or the PLZF (for promyelocytic leukaemia zinc finger), locus, are oncogenic and result in human acute promyelocytic leukaemia (APL). PML-RAR-alpha APL patients achieve complete remission following treatments with pharmacological doses of retinoic acids (RA); in contrast, PLZF-RAR-alpha patients respond very poorly, if at all. Here the authors report that the association of these two chimaeric receptors with the histone deacetylase (HDAC) complex helps to determine both the development of APL and the ability of patients to respond to retinoids. Consistent with these observations, inhibitors of histone deacetylase dramatically potentiate retinoid-induced differentiation of RA-sensitive, and restore retinoid responses of RA-resistant, APL cell lines. The authors' findings suggest that oncogenic RARs mediate leukaemogenesis through aberrant chromatin acetylation, and that pharmacological manipulation of nuclear receptor co-factors may be a useful approach in the treatment of human disease. R J Lin, L Nagy, S Inoue, W Shao, W H Miller Jr & R M Evans Role of the histone deacetylase complex in acute promyelocytic leukaemia (Letter to Nature) Nature 391, 811 (1998)

To: Zeuspaul who wrote (15296)	2/19/1998 8:00:00 AM
From: tonyt	Respond to of 32384

I see you're back -- I guess you only post when LGND is up -- Why?? (I guess you'll only be around for a few more days) I'm also curious if you were buying at $11, or were you just hoping to someday get back in the black? > I think Tonyt suggested once In at 14 out at 16. Did you take my advice? If so, you made 14% in one day when you sold at $16 last week and bought back in at $14 the next day -- Congratulations! P.S. LGND (not LGNDW) is a great trading stock, if you don't get caught-up in this triple dight nonsense and 'drive to 25' garbage you can make a ton of money -- Just don't get emotional, otherwise you'll never make money in LGND. Good Luck! --Tony

To: Zeuspaul who wrote (15296)	2/19/1998 8:26:00 AM
From: Henry Niman	Read Replies (2) \| Respond to of 32384

Here's another Evan's paper showing a similar synergy in another type of cancer (myeloid leukemia): Cell 1997 May 2;89(3):373-380 Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase. Nagy L, Kao HY, Chakravarti D, Lin RJ, Hassig CA, Ayer DE, Schreiber SL, Evans RM The Salk Institute for Biological Studies, La Jolla, California 92037, USA. The transcriptional corepressors SMRT and N-CoR function as silencing mediators for retinoid and thyroid hormone receptors. Here we show that SMRT and N-CoR directly interact with mSin3A, a corepressor for the Mad-Max heterodimer and a homolog of the yeast global-transcriptional repressor Sin3p. In addition, we demonstrate that the recently characterized histone deacetylase 1 (HDAC1) interacts with Sin3A and SMRT to form a multisubunit repressor complex. Consistent with this model, we find that HDAC inhibitors synergize with retinoic acid to stimulate hormone-responsive genes and differentiation of myeloid leukemia (HL-60) cells. This work establishes a convergence of repression pathways for bHLH-Zip proteins and nuclear receptors and suggests this type of regulation may be more widely conserved than previously suspected. PMID: 9150137, UI: 97294381

To: Zeuspaul who wrote (15296)	2/19/1998 8:32:00 AM
From: Henry Niman	Respond to of 32384

Zuespaul, The credibility of some posters come and go because they day trade and love to see LGND's price gyrating up and down. Of course they would like to see this pattern continue, so they continually discount long term moves and investors and try to get them to join their trading strategy, even in the "off season", when they had recently indicated was a time to stay on the sidelines: Message 3303672 Although it's been unseasonably warm, it's not quite like August and my calendar still says February.

To: Zeuspaul who wrote (15296)	2/19/1998 10:11:00 AM
From: tonyt	Respond to of 32384

Something to consider when deciding if you should 'buy and hold': Since this thread started, LGND is down 4%. There is no better argument for trading at least some of your LGND position (or at least sell covered calls) Good Luck --Tony P.S.: Check out DELL - up $6+

To: Zeuspaul who wrote (15296)	2/19/1998 11:28:00 AM
From: tonyt	Respond to of 32384

Did you check out DELL?? Up $8 now!

To: Zeuspaul who wrote (15296)	2/19/1998 11:53:00 AM
From: tonyt	Read Replies (1) \| Respond to of 32384

DELL now up 9 1/2 (up 3 1/2 from when I said to 'check it out')

To: Zeuspaul who wrote (15296)	2/20/1998 7:39:00 AM
From: Henry Niman	Respond to of 32384

The current issue of Cell has a couple more articles on histone acylation and deacylation: Rb Interacts with Histone Deacetylase to Repress Transcription Robin X. Luo, Antonio A. Postigo, and Douglas C. Dean 463-473 Activation of SRF-Regulated Chromosomal Templates by Rho-Family GTPases Requires a Signal that Also Induces H4 Hyperacetylation Arthur S. Alberts, Olivier Geneste, and Richard Treisman