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Isis Pharmaceuticals, Inc. Message Board

jetmanbash 164 posts  |  Last Activity: 2 hours 43 minutes ago Member since: Dec 29, 2004
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  • Akt confers cisplatin chemoresistance in human gynecological carcinoma cells by modulating PPM1D stability
    Molecular Carcinogenesis, 09/11/2014 Clinical Article

    Ali AY, et al. – Ovarian cancer (OVCA) and cervical cancer (CECA) are lethal gynecological malignancies. Cisplatin (CDDP) and platinum derivatives are first–line chemotherapeutics, and their resistance impedes successful treatment. It has been established that protein phosphatase magnesium–dependent 1 D (PPM1D) confers CDDP resistance in gynecological cancer cells by deactivating p53. This study has established that PPM1D plays an important role in promoting CDDP resistance, and as a novel downstream target of Akt (also known as protein kinase B), PPM1D mediates its action in conferring CDDP resistance in gynecological cancer cells.

    Key Findings

    CDDP induced PPM1D down–regulation through proteasomal degradation in sensitive CECA cells.
    CDDP induced PPM1D nuclear localization in resistant CECA cells, and nuclear exclusion in sensitive CECA cells and OVCA xenografts.
    Over–expression of active Akt in sensitive CECA cells stabilized PPM1D content through inhibition of CDDP–induced PPM1D down–regulation.
    Inhibition of Akt activity in resistant OVCA cells leads to decreased PPM1D stability and CDDP–induced down–regulation in resistant CECA cells.
    PPM1D is highly expressed in human ovarian tumor subtypes and in a tissue microarray panel of human ovarian tumors.

    Have to throw in some spamming on ISIS, will be over 100 by second half of next year. t

  • Reply to

    did Rexahn ever provide news on this

    by bcpiii Aug 9, 2014 1:51 PM
    jetmanbash jetmanbash Aug 9, 2014 5:33 PM Flag

    These ligand delivery systems can get up to 60 fold more drug to the target than without their use. In regards to ANS and RNAi these carriers are all the rage, and for good reason. You couple maybe the number one biomarker for CA....AKT1 along with this elegant potent system and you may not hit on all targets with success, but your chances for several are quite good IMO. t

  • There were no less than four children on this telethon espousing the virtues of ISIS drug for SMA. These kids and their families have seen notable improvement in their lives with the advent of their using this drug for SMA. In the interest of human suffering and the chance for a treatment that will effect their lives, as evidenced by this nationally televised MDA Telethon I'd ask that the detractors and shorts disperse. They are going to lose the battle anyway, and everything they try and do to ruin ISIS reputation and chance for success could end up hurting this children. t

  • Both GILD, and ONCY announced that their drugs failed in pancreatic CA. If RNN can be this demon as the best in class many of us won't have to worry about retirement. t

  • Constitutive AKT activation in follicular lymphoma Full Text
    BMC Cancer, 08/20/2014 Clinical Article

    Yahiaoui OI, et al. – The phosphoinositide 3– kinase (PI3K) pathway is involved in the growth of various human cancers, including lymphoid malignancies. This resear5ch aimed to find out its role in the pathogenesis of follicular lymphoma (FL). The data suggest that the PI3K/AKT signaling pathway could be activated in a subset of FL cases, due to either AKT phosphorylation or PTEN downregulation, in the absence of PIK3CA mutations.

    •To clarify this point, biopsy tissue samples from 38 human FL cases were investigated for PIK3CA somatic mutations in exon 9 and 20 using direct sequencing.
    • The same samples were analyzed using western blotting and immunohistochemistry to detect expression of AKT, phosphorylated AKT (pAKT), and PTEN proteins.
    • Two cases of benign lymphadenitis were used as controls.

    • AKT expression was present in all FL and lymphadenitis cases.
    •14/38 (37%) FL and 2/2 lymphadenitis cases expressed pAKT.
    •9/38 (24%) FL samples showed high level of pAKT, whereas 5/38 (13%) FL cases and 2/2 benign lymphadenitis samples expressed low level of pAKT.
    • PTEN expression was observed in 30/38 (79%) FL and 2/2 benign lymphadenitis cases, whereas 8/38 (21%) FL cases showed loss of PTEN expression.
    •3 cases with positive pAKT did not express PTEN. PIK3CA mutations were not detected in any sample.

  • All of the vicl minions are going to be continuously jealous as this plays out. They have programs for HD, ALS, TTR-amyloidosis, etc. Their flag-ship product their ApoCIII inhibitor lowers ApoCIII by 80% which is a CV risk factor in and of itself. It lowers your triglycerides by 75%, raises your HDL by 55%, decreases insulin resistance, and will have maybe two or more orphan indications and then go mainstream. The triglyceride/HDL ratio may be the most important ration in regards to CV risk. A recent published paper on this drug was supported by NovoNordisc. They could be the eventual owners of this drug. An upfront payment of from $500 to $700 million with milestone payments, and double digit royalties for the mainstream use and ISIS might keep the one or two Orphan indications for themselves. t

  • jetmanbash by jetmanbash Jul 21, 2014 10:09 PM Flag

    The company can hold out without a partner and still advance their drugs in the lab the higher the price will be when they do partner their drugs. This is a three investment IMO. Don't let people dissuade you from you goals. There has been no bad news, and recent news was relatively good. Time and patience is what is needed. Will continue to follow this stock and give updates. Plan a calling their IR soon. Some dumbos who don't know anything and say the stock sucks without any validation are zzzzzz. t

  • jetmanbash jetmanbash Sep 12, 2014 9:03 AM Flag

    I can't even make a pancake, but if you want yo play twenty questions this what I do. I have a question for you. What is the only cranial nerve that completely decussates and where? Believe what I post or don't. t

  • jetmanbash jetmanbash Sep 12, 2014 9:03 PM Flag

    NOT from vicl, they have only had a recent study where the placebo badly outperformed the treatment group. The info was delayed as long as possible by the CEO, but finally he came out kicking and screaming and had to admit that the placebo did in fact do a better job than the treatment group. But that was over six months ago. Since that time the company has had little or no news and the whole world in vaccine medicine has passed them by. t

  • Please let me know how vicl and ISIS are doing price-wise. TIA, t

  • Down-regulation of miR-29c in human bladder cancer and the inhibition of proliferation in T24 cell via PI3K-AKT pathway
    Medical Oncology, 07/11/2014

    Fan YR, et al. – This study explored new tumor suppressor microRNA in bladder cancer and conducted a functional analysis of its suppressive role. It found that miR–29c could be an active player in the disease state and may be a promising tumor suppressor in bladder cancer.

    Methods and Results
    •To investigate the expression of miR–29c, qRT–PCR was used in 30 pairs of bladder cancer tissues and normal tissues (adjacent bladder tissue samples).
    •The expression of miR–29c was down regulated in bladder cancer tissues compared with normal tissues.
    •Low–level expression of miR–29c was associated with tumor stage (P=0.002), and ectopic over–expression of miR–29c in T24 cells can significantly inhibit cell proliferation, decrease motility, suppress the G1/S cell cycle transition and induce apoptosis.
    •It could also cause a decrease in AKT and GSK–3β phosphorylation.
    •While LY294002 reduced the protein level of pAKT, the over–expression of miR–29c can further decrease its level in T24 cells pretreated with LY294002.
    •The proliferation inhibition of T24 may take place via AKT–GSK3β pathway.

  • jetmanbash by jetmanbash Jul 23, 2014 9:11 PM Flag

    Glad I sold my VICL and put it all in INO about three months ago. Predict VICL will be $1.80 by Jan 1st, ISIS will be $75. Wondering when VICL will pass ISIS in price..........maybe maybe by the year 3001 when the ice age comes back. In the meantime, I'm going to by a lot of other biotechs besides VICL. t

  • jetmanbash jetmanbash Jul 26, 2014 11:27 AM Flag

    You'd be best advised to follow your own advice and SCRAM back to the vicl won't happen and that is why I say death to vicl and the sooner the better. t

  • Reply to

    Like the say in China "vicl no good."

    by jetmanbash Jul 27, 2014 7:48 PM
    jetmanbash jetmanbash Jul 27, 2014 7:52 PM Flag

    What a zero company vicl is. They have been out as long as ISIS and they have a price tag of a buck and change and they are going to zero. The sooner the better as this board can then maybe discuss real ISIS topics rather than vicl sxxx. Hope Pearl acts quickly. Have also asked that anyone who concentrates on prune juice be forever cursed with diarrhea and be forced to move in with women who have the same. t

  • jetmanbash jetmanbash Aug 1, 2014 7:01 PM Flag

    You will continue to sleep well at night with your vicl even after it goes bankrupt, your physician will just have to double your Ambien. t

  • jetmanbash jetmanbash Jul 26, 2014 11:24 AM Flag

    This isn't an Fxxxing trial in regards to ISIS or some government mandate. They are making huge progress at ISIS and even the RNAi blogger has come around and sees ISIS as the most powerful force in RNA at this time. Within two years they could have drugs on the market that is very valuable. No, the only way to rid the board of this from people like you is for VICL to go BK.......and I'm hoping and watching for that to happen. More so now than ever. Chances are high too. One more failure in the lab and they will be done. The good American workers there can probably latch onto another biotech. The CEO is highly suspect with running a trial and holding back on the info where the placebo patients did better than the treated patients. Short live VICL the sooner they die the better. And I'm waiting for it anxiously. Maybe a big failure by this year and they get delisted from the NSAD.......they are close now, no matter what spin you try and put on......t

  • miR-29b suppresses proliferation, migration, and invasion of tongue squamous cell carcinoma through PTEN-AKT signaling pathway by targeting Sp1
    Oral Oncology , 08/29/2014

    Jia LF, et al. – miR–29b has been implicated in various cancers. However, the role of miR–29b in tongue squamous cell carcinoma (TSCC) remains unclear. This study found that miR–29b functions as a tumor suppressor in TSCC, and the miR–29b/Sp1/PTEN/AKT axis may represent a potential therapeutic target for TSCC intervention.

    •The expression of miR–29b was analyzed in TSCC tissues and cells.
    •Functional studies were performed in TSCC cells.
    •Real–time PCR, Western blot, cell proliferation, transwell, and dual luciferase reporter assays were performed according to standard procedures.

    •miR–29b was significantly decreased in TSCC specimens and cell lines compared with corresponding normal counterparts.
    •Overexpression of miR–29b significantly inhibited the proliferation, migration, invasion, and cell–cycle progression of TSCC cells, and promoted apoptosis.
    •Moreover, miR–29b targeted the 3' untranslated region of the Sp1 transcript and resulted in the deregulation of Sp1.
    •The inhibition of Sp1 by miR–29b subsequently resulted in the upregulation of PTEN, leading to a decline of phosphorylated AKT.
    •Knockdown of Sp1 in TSCC cell lines mimicked the effects of miR–29b overexpression.
    •The expression of miR–29b was inversely correlated with Sp1 and positively correlated with the PTEN in TSCC specimens.

  • jetmanbash jetmanbash Aug 29, 2014 8:41 PM Flag

    Again another article in the literature showing the importance of AKT in CA. MACK is working on inhibition of this target as well so we need to keep an eye on them and their progress as well.

    Activated PI3K/AKT and MAPK pathways are potential good prognostic markers in node-positive, triple-negative breast cancer
    Annals of Oncology, 08/29/2014 Clinical Article

    Hashimoto K, et al. – Triple–negative breast cancer (TNBC) patients are a poor prognostic subgroup, and currently, there is no biomarker for targeted therapy. The authors determined that tumors expressing pAKT or pERK are a good prognostic subtype in node–positive TNBC. Different targeted therapies may be necessary for TNBC that involves activation of PI3K/AKT or MAPK pathways.

  • Targeting the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin(mTOR) pathway: an emerging treatment strategy for squamous cell lung carcinoma
    Cancer Treatment Reviews, 07/14/2014  Review Article  Clinical Trial Below

    Beck JT, et al. – This review will discuss therole of the PI3K/AKT/mTOR pathwayin cancer and how the discovery ofgenetic alterations in this pathway in patients with squamous cell lung carcinoma can inform the development of targeted therapies for this disease. An overview of ongoing clinical trials investigating PI3K/AKT/mTOR pathway inhibitorsinsquamous cell lung carcinoma will also be included.

  • Reply to

    Scam articles

    by pipewrench65 Jun 28, 2014 6:44 PM
    jetmanbash jetmanbash Jun 29, 2014 10:22 AM Flag

    For VICL they have 24 years of only a drug to keep my dog safe from melanoma of the mouth, and not much else to show for it. Moverover, they are falling behind other vaccine based biotechs in the science of better vaccines. They are one more failure away from BK. You don't seem to know too much about the competitors in regards to vaccines, but by your name you seem to think so. VICL is about 17 cents off its low for the year, about 75% lower in value since this recent bull market started about four to five years ago, they have had several big failures, no deals, their competitors have grown in number and prowess, the technology used by others is superior, they have lawsuits in regards to how their CEO handled their last failure, and he was considered last year's worst CEO in the WHOLE biotech space........I don't see how a biotech could do worse, but what is even more stunning is how you can continue to promote it with that background. The problem with business in general, and really biotech in particular is that once you get behind the technology curve it is almost impossible to catch back up and get competitive again. You can keep pushing this trash, but another year of more of the same with VICL not doing anything and you will really look even worse than than you do now........if that is even possible. t

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