I will take a hit for the team here.
Okay... I saw whytee change his mind pretty quickly and he didn't actually get hit but he took a bit more rhetorical flack than you'll have to take.
I'm pretty tired now - when I first read you comment I thought it was funny, that you were just agreeing to shut me up but that you hadn't actually changed your mind. And I was fine with that and ready to move on because even ironic agreement or false agreement or ambigous agreement looks like straight agreement to a lot of members of a group. I could have just moved on.
But if you look at Bazsa reply he's answered that he think its both. So he thinks Mesoblast's authors are saying the sentence (which I agree with). But Bazsa has also agreed to the suggestion that its a quote. But its not a quote. (That exact sentence would have be in reference [7] for it to be a quote.) A citation is not a quote. Its not both. Bazsa is coming in behind your former (?) position that a citation is a quote. But also mine that its a statement. But this isn't politics its logic.
If you look at PL89's reply - he is pointing at the [7] citation. So he thinks (as near as I can tell - he says the answer to my question is right there (but I asked a several) that Aggarwarl and Pittenger 2005 are saying it. He seems to think I'm missing the obvious.
Had the [7] been left off, had no annotated citations been included tat all he statement would still be valid and would still be Mesoblast's (the authors shared) asserted opinion.
Mesoblasts statements are of course their own statements, whether they be about other peoples' scientific work, or their very own scientific work, or any topic.Of course.
And I'd have left things there but Bazsa and PL89's comments show some reading still don't see a difference between a citation to support a new statement (the sentence in Kasikis et al in 2021 is a new statement) and a quotation which literally restates something from someone else earlier. Science papers are not English literature.
For clarity will you please state that you were wrong to equate or conflate a citation with a quotation?
In the TNFR1 patent application there is at least one statement that doesn't have any citation to back it up - and in my opinion, (which could be wrong I admit), its wrong in suggesting TNF-a induces IDO enzyme activity.
But there is no question the truth or falseness of the claim is important. And MSB says they
have accumulated data.
Its this one, in yellow - I'll give you the whole paragraph for context.
"[005] the TNF-a receptors are expressed on the surface of
mesenchymal stem cells. Accumulated data indicate that
TNF-a is an important regulator of mesenchymal stem cell
function. Incubation of TNF-a with human mesenchymal
stem cells in culture upregulates prostaglandin E2 (PGE2)
and kerinocyte growth factor (KGF) secretion, induces
indoleamine 2,3 deoxygenase (IDO) enzyme activity and
stimulates cell migration. TNF-a has been shown to be
present at wound and inflammatory sites, especially in
organs targeted by graft-versus-host-disease. (Kiode, et al.,
Transplantation, Vol. 64, pgs 518-524 (19997); Kuroiwa, et
al., J. Clin. Invest., Vol. 107 pgs 1365-1373 (2001); Deans,
et al., Exp. Hematol., Vol 28, pgs 875-884 (2002); Ellison,
et al., J. Clin. Immunol., Vol 24 pgs, 197-211 (2004)). Thus,
such data indicate that expression of TNF-a receptors by
mesenchymal stem cells may be critical for immunosup-
pressive, immunomodulatory, anti-inflammatory, tissue-re-
pairing, or wound-healing activities, as well as migration to
sites of inflammation."
Now dachopper you referred me to that patent pending.
US 2021/0171913 A1.
It was last updated Jun 10, 2021.
I don't believe TNF-a does induce IDO enzyme activity.
I think that IDO is activated through an INF-gamma receptor.
I think there is very good science showing INF-gamma going
to JAK stat pathway and so on - and there can be interplay between
separate pathways like the TNF-a - TNFR1 to NKkappaB
pathway - but such interplay between the TNF-a and IDO is
either very subtle and complicated or it doesn't actually happen
that way.
How all this bears on the potency assay is that the potency assay
needs to causally linked not just linked (just linked could be a correlation
without a causal link) to the potency of the product. So its important
to get confounding out of the potency assay itself.
Is it possible to get INF-gamma confounding out of the potency assay
- in my opinion it should be if you were going forward with a trial
from now, but doing it after the trial is a whole different level of difficult
because you have to have enough material to work with.
In my opinion its pretty clear TNFR1 antibodies were an issue that was
associated with the potency assay problem Dr Rose mentioned - though
he didn't say it was that. That's, in theory fixable. We've talked about that.
But if you have to data mine the same retained samples to also show that
INF-gamma is not confounding your survival data to potency assay causal
linkage - that's another complication again and likely would put a further
demand on your retained samples.
MSB at ODAC went with just two parts to their potency assay matrix
- TNFR1 and IL2Ralpha inhibition.
I don't think either of those components can tease out the INF-gamma
influence from the TNF-alpha influence on the mechanism of action.
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