I know that the breast and lung cancer studies were not as limited as the Myelofibrosis trial, but they were of a small group nonetheless. What one composes here and what Yahoo takes out on the other end, and the editing to compensate often leaves me with an odd statement or two when posting.
The only way that any statistician can argue that the drug failed is to say that within this small population of patients who were quite sick and resisted conventional treatment, and yes, among them it failed. This tells me that you are not a statistician because you conclude this for the larger population; thus, you do not have the statistical support to argue otherwise. Hello, too, with your probability argument about success of the efficacy! This is not what a good scientist would expect from a statistician: " perhaps even more so, drive the efficacy % down because of the small number and average likelihood of success of any pharmaceutical." How can you argue this nonsense as a statistician? That is a good null hypothesis. But is the population representative of the general population at large of those who suffer from myelofibrosis, or breast, lung cancer of the types, which were studied, instead of the very sick resistant population of patients who happened to be existing patients, or easily recruited under the protocol for one site, namely the Mayo Clinic, or who happened to already be there for alternative or conventional treatments? Phase I clinical trials consist generally of a very small population of patients to test safety and establish dosing for efficacy. Trials expand in phase II and phase III. (Following phase III data and analysis, then you could make an argument about percentages, which would be more applicable to general populations as you jump to here and now.) What I gather from this is that Geron was looking for market share or competition for a market niche for whatever was left over to take on and take to the market place. Regarding success, market share and launch window are big items for pharmas and often are not about efficacy beyond the threshold for treatments.
I am with you on MOVING AHEAD faster than Geron seems to want to move, and the bonuses should come after we secure FDA approval, buy out or partnership!
You're welcome! There is more. What about the shelterin complex in these cancers, and induced cancer tissues and cell lines? Google this:
Understanding the Role of Functional Telomere Structure in Aging by Single Molecule Imaging by Ahmet Yildiz PhD
University of California - Berkeley, 2009 new Scholar Award in aging
Note: "Recent studies showed that ___ telomere structure, ___ ___& this makes sense with molecular structure & shape affecting molecular behavior___ not the telomere length is the main determinant of senescence setpoint. Telomere binding proteins form the shelterin complex which helps the formation of a protected telomere structure and regulates telomerase activity. ___ Large number of associated proteins and their highly stochastic and dynamic interactions with telomere limit the ability of conventional the structural studies. Therefore, detailed mechanism of functional telomere assembly and its replication by telomerase has not been fully addressed due to the technical difficulties.
This is how it begins, and the results of this study tell us that it is a likely drug for treating this disease. I am willing to bet that imetelstat has efficacy in treating this cancer. What particular biomarkers were identified, if any, in these cell lines, might be very useful. "These results show that continuous exposure to GRN163L can reverse the immortal phenotype of pancreatic cancer cells. These findings should facilitate the design of future clinical trials of GRN163L in patients with pancreatic cancer." For me, this supports my argument that imetelstat has broader applications for cancer treatments beyond myloproliferative disorders; however, let's not confuse "reverse" with cure.
Do not forget the study in Europe with ET, and how that data should support the efficacy, safety, and dosing of imetelstat for combating myloproliferative diseases. See this:
ClinicalTrials gov identifier: NCT01243073
California, City of Hope, Duarte, California, United States, 91010
Orlando, Florida, United States, 32806
United States, Illinois, University of Chicago, Chicago, Illinois
Maryland, Johns Hopkins University, Baltimore, Maryland, United States, 21205
Mount Sinai School of Medicine - Tisch Cancer Institute, New York,
N. Y., United States, 10029
Saint Francis Hospital, Greenville, South Carolina, United States, 29601
MD Anderson Cancer Center, Houston, Texas, United States, 77030
University Hospital of Essen - West German Cancer Center, Essen, and Medizinische Klinik II, Abt. Hämatologie und Onkologie - Johann Wolfgang Goethe Universität, Frankfurt, Germany, D-60590
Heilbronn, Germany, Hematology Oncology Center - Ludwig-Maximilians, University Munich Medical School, Munich, Germany, 80331 & University Hospital Regensburg - Uniklinik Regensburg, Regensburg, Germany
Switzerland, University Hospital Bern, Bern, Switzerland, CH - 3010
Continued, part 3 of 3:
Oligonucleotides with various chemistries have been tested and N3′-P5′ thio-phosphoramidate oligonucleotides have yielded some of the most potent and selective inhibitors of telomerase __Key words __. Source: plosone org article info 3Adoi 2F10 1371 2Fjournal pone 0085155
Could it be that some biochemical pathway interfers with telomerase inhibitor molecules, or binds with it in a manner that blocks the effect of the molecule used by Anderson's team that might not intefere with an oligonucleotide? Also, remember this basic fact, mice normally have higher levels of telomerase activity than do humans in mature, ordinary functioning cells or tissues. Well, in recent weeks on this board, some have discussed the problems with the breast cancer study in mice with imetelstat and how some folk concluded too much from a study with mice with induced cancer ___ as we examine here in Anderson's research. In short, what telomerase inhibitor did Anderson's team use? Are all telomerase inhibitors the same? I think not. Unlike you, I await more data.
Continued, part 2 of 3:
I read the article by Anderson, which was posted online. However, the methodology was not published in what I read. Consequently, I have many questions. Firstly, what telomerase inhibitor was used, such as a small molecule telomerase inhibitor, BIBR1532, or was it a larger molecule, oligonucleotide? Molecular structure matters in chemistry, and in the physical environment. Do you assume that all telomerase inhibitors are the same and that these function in the same manner? Secondly, was there some other biochemical pathway tied to the genetics of the induced cancer tissue culture that blocked the telomerase inhibitor, or how did that particular molecule work in Anderson's study? This is worth mentioning, BTW: mitochondria have their own DNA, which is smaller than regular cellular DNA and which is comparable to prokaryotic DNA and likely evolved from those organisms, and must divide, as do cells to keep tissue growing, or functional over time.
Here is what the Jan. 7, 2014 researchers had to say about telomerase inhibitors: Human telomerase contains two essential subunits: the protein hTERT (human Telomerase Reverse Transcriptase) and the small nuclear RNA hTR (human Telomerase RNA). The first provides catalytic activity and the second contains a short sequence _ 5′-CUAACCCUAA-3′_ that serves as a template for the synthesis of telomeric repeats. The substrate of telomerase is the single-stranded 3′-telomeric overhang that caps the very end of all telomeres. The enzyme functions as a reverse transcriptase and uses the RNA hTR as a template for the synthesis and addition of telomeric DNA repeats to the 3′-telomeric overhangs. For telomerase inhibition, the template region of the human telomerase RNA _ hTR _ presents an accessible target for oligonucleotide-based inhibitors. Oligonucleotides DESIGNED ___ important ____ to hybridize to the template region can be used to inhibit the activity of telomerase. Oligonucleotides with
Scistats, I disagree, and again my problem with your science is that its strength is in using specific study results for drawing broader conclusions, while ignoring methodology, peer review, statistics, or arbitrarily selecting this, that or the other to arrive at some general conclusion, which cannot be supported by any aforementioned items. Are you playing on the ignorance of others here? The 20% population for CRs and PRs in Tefferi's research was from October, as I recall, and it seems to me that this percentage could increase as the diversity and size of the clinical study continues to expand along with the duration of treatment, and why would it not? You draw broad conclusions with much certitude far too soon, and you ignore the population size and character. Your science seems to be too far north or south of the Tamar and must be under water. I need to know far more than I find at present to draw the same conclusions that you draw from one study of mice. I tend to think of suspended conclusions, instead of the absolute ones that you tend to pervade on this board.
I read the article by Anderson, which was posted online. However, the methodology was not published in what I read. Consequently, I have many questions. Firstly, what telomerase inhibitor was used, such as a small molecule telomerase inhibitor, BIBR1532, or was it a larger
Help me understand why the underlying problem does not lie within people, and wherever you find people, you find corruption? Where is this Utopia that you people believe exists once you remove government? I submit that the private sector is far more corrupt than government and that anyone who thinks otherwise, is NOT informed, period. I do not assume government has cornered any market on corruption. Take a look at the internet and how private sector corruption is an underlying part of the corruption. Look at this board and the corrupt, selfish liars who try to run over us. What is to keep corrupt people from running over anyone else? The government did not recently hack into one a computer system and get one of my credit cards and make fraudulent charges, but a thief among us, did so. We must have government to thwart the corruption that exists by default within humanity. This Utopia, which will exist once government is removed. is a MYTH. We need to alter government, so that it will do a better job.
Don't forget pancreatic cancer, and see my recent post with a link to a Feb. 14th article on myeloid ___stem cells ____ and solid tumor progression. Others here seem to fail to realize the combo drug toxicity that resulted in previous trials, established trial protocol, and the disease stage when imetelstat was applied to treat cancer. Many of those folk were very sick, and did not respond to conventional treatment. So, it was a difficult task to take on such cancer, and not just a test for efficacy as much as it was for market share.
For some readers here, I have jumped over a few important bits of information. If the myeloid cells are augmenting tumor growth, as indicated in the my link above here, then imetelstat in whatever dose 4.5, 7.5 or 9.5 depending on the tolerance of the individual could be used to suppress the myeloid production, while another drugs takes on the tumors. Again, this article tends to indicate support for broader applications for imetelstat.
Yadda, yadda, yadda....more barnyard fodder. You are frustrated because it is not easy for you to manipulate this board for your personal gains. Go drive down the price of oil and make yourself useful to others.
How about even getting a Q4 2013 report and when we might expect that to be announced? Can you help them understand the importance of a conference call and updates to the shareholders?
Rattle, here's what I am thinking regarding the application of imetelstat. I agree that it is likely that the myeloid cells are normal. However, what is one of the side effects of imetelstat or what does it do? It is known for myelosuppression as are other chemotherapy drugs. So, this link as I see it now shows support for and opens possibilities for combo drug development down the road for imetelstat for treatments of other cancers beyond blood cancers. This adds to the value going forward for this stock. IMHO and what are your thoughts?
I'm with you on the focus. However, should there be a buy out then the other possible applications for imetelstat, Sienna Cancer Diagnostics, and hESCs ought to be factored into the final share price. The current price per share is about 50% below a fair price considering the value of INCY at $67. Let us hope for "BreakThrough" approval with the FDA.
It seems to me that they are scammers who are out to find a flaw in your computer security and get at one's financial accounts, ID and so forth. Why is it that these jerks get to ram their way of scamming down our throats? Find a way to fight back and do it in every way that you can. Hit the "Flag" for reporting abuse here and let get their scamming butts off here.
Why do the garbageheads get to run over us here? Go pick on the oil companies and help us all by undermining them.
Wheeeeeee, I finally got this past the Yahoo computers....
More.............Tumor - infiltrating myeloid cells activate Dll4 Notch TGF-β signaling to drive malignant progression __had to remove all forward slashes in the title__
Hidetaka Ohnuki1, Kan Jiang1, Dunrui Wang2, Ombretta Salvucci1, Hyeongil Kwak1, David Sanchez-Martin3, Dragan Maric4, and Giovanna Tosato1,*
Author Affiliations: 1Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, 2W2MOTIF, 3LCO, NIH
4Intramural Research, National Institutes of Neurological Disorders and Stroke, National Institutes of Health. Corresponding Author: Giovanna Tosato, Laboratory of Cellular Oncology, National Cancer Institute