Replies to post #280169 on Avid Bioservices Inc (CDMO)

[biopharm]

FIND NEW TARGETS RE: TM4SF1 (PS Targeting...)

Now with VEGF one seems to forget that it has TWO functions and not ONE. If someone will act on VEGF then it must be done in a way that angiogenesis is stopped but vascologenesis is NOT affected. Certainly in people (children to young adults till the age of about 21) that have non full grown vascular systems need vascologenesis for the formation of their vascular system.

And if angiogenesis is a feature of our bodies then that means it is NEEDED for something. It grows blood vessels starting from a vascular ancker-point. Hence one sees it start in the endothelial and make its way from there to form a network of blood-vessels of which the tumour can feed.

CP, thanks for the post and I only took a small clipping of your post above.... and I've been digging deeper into areas of VEGF, basically because of Peregrine KOL Harold Dvorak.

I will not yap on and on in this post, but will advise all to watch this video:

Peregrine KOL Harold Dvorak - video below 38 min in length-- a MUST WATCH:

I found it to be a very nice recap of the history of fighting cancer and I do get a better impression of Dr. Harold Dvorak than I do of Peregrine KOL Bruce Chabner... at this time, but I wonder why I have not heard the term Phosphatidylserine or flipped PS when I KNOW that Dr. Harold Dvorak knows well of it and I do give some leeway that Peregrine is working on breaking down the patents and require their KOL's to do so as well.

Some key comments from this video - 38:58 in length

8:00 mentions that years ago there were no such thing as Bcells ot Tcells.....just were called "lymphocytes"

9:00 studied tumors as an antigen

9:30 FIBRIN

10:30 How do you get Fibrin? (...tumor vessels have to be leaky and clotting proteins...etc)

11:30 Tumor cells on their surface exress TF (tissue factor) and shed microparticles (now called exosomes..) that also express TF...extravascular clotting taking place

17:00 During clotting... plasma changes to serum

19:00 Tumors are wounds that do not heal

21:00 Tumors are targetable

22:30 ..makes mention of Avastin/Genentech $6B/year

22:30 What are tumor blood vessels...

23:00 How do tumor vessels form (Mother Vessels...)

26:30 Mother Vessel => 1st vessel that forms in tumors and wounds (strokes...not some little finger cut..)

Why doesn't anti-VEGF work better?
1) Tumors co-opt pre-existing vessels (make use of current ones)
2) Tumors survive hypoxia and need few new blood vessels
3) Not all blood vessels are equally susceptible to anti-VEGF/R therapy

32:30 FIND NEW TARGETS => TM4SF1 ... and pay close attention how he says they were disappointed "initially" when they found that TM3SF1 was also express in normal vascular endothelium cells, but hmmmm, flipped PS was always found internal to cells and bingo...

-------------------------------------------------------------

Phosphatidylserine Increases IKBKAP Levels in Familial Dysautonomia Cells

Dec 29, 2010

(3rd paragraph under "Discussion" section..)
The gene expression array analysis revealed that levels of expression of a large number of genes were altered due to PS treatment. [color=red]It is not surprising that PS affects genes other than IKAP, and these effects may be direct or indirect. Kinetin, for example, was shown to affect splicing of other genes [24], and many genes change their expression level in IKAP-deficient cells [20], [21], [39]. Of particular interest in the list of genes demonstrated to be affected is the TM4SF1 gene, a transmembrane 4L six family member, also known as L6-Ag, that influences cell motility [/color][46], [47]. It is possible that the PS-induced increase in TM4SF1 mRNA levels increases IKAP levels through regulation involving cell migration, which is impaired in Elongator-depleted cells
..
..
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012102/

Tumour-associated antigen L6 (L6-Ag, also known as TM4SF1)

https://www.ncbi.nlm.nih.gov/pubmed/18270265

I know I said I would not yapp on and on.... but PS Targeting is obviously related to TM4SF1 !! and here we have the KOL of Peregrine who knows well of PS Targeting and now throws out there "we need new targets..." and comes up with the sidekick of flipped PS...

I will say at the very end of the video, Dr. Harold Dvorak did make mention that "there may be other targets..." as well but made no mention of them and I believe that this is truly as close to some manhattan project one can ever find and its plain as day right in front of us all.

I hope Sean Parker and others continue to push the envelope and keep pressure on all fronts. Big Pharma still would be, my guess.... trying to hold back PS Targeting as much as possible... but now we wait for Dec 7... more biomarkers to come.