Replies to post #124168 on Avid Bioservices Inc (CDMO)

[sulaco]

EBS, give me a sec, I'm on another computer

and don't have my bookmarks of links on this one. I'll get to you in a sec.


As an aside, here's an interesting study on tumor hypoxia that reveals its incredible complexity (unlike Vinmantoo's sloganeering)


http://www.biomedcentral.com/1471-2407/11/331

Some highlights:

Recently we unexpectedly found that hypoxia (10% O2) strongly inhibited tumor growth of lung cancer in nude rats. We therefore extensively investigated the role of hypoxia in tumor progression in this study. We hypothesized that hypoxia may not be a factor favoring tumor progression of lung cancer.

A recent report showed that systemic hypoxia promoted prostate cancer growth in mice [29]. However, another study found no significant change either in primary tumor growth or in lung metastasis in a transgenic mouse breast cancer model after exposing the mice to hypoxia [30]. Therefore, in spite of much work done in different laboratories, the precise role of hypoxia on tumor progression is far from being completely understood [31].

You can see how simplistic Vinmantoo's opinion becomes in light of this. Hypoxia can in fact NOT be involved in tumor progression AT ALL. (That splash you heard is Vinman being blown out of the water.) It can be acute. It can be chronic. It is poorly understood in any case. And yet Vinman Mickey Mouse has it ALL figured out.

[sulaco]

Here are my thoughts, EBS

The protein binding that everts PS gets pretty darn complicated in a hurry.

However, I'll give it a try:

My thoughts originally came from the Phosphatidylserine Asymmetry Presentation. It's from the NYAS link.
http://www.nyas.org/publications/EBriefings/Detail.aspx?cid=8f6e304e-f219-4238-b555-bd2e4212f94a

(I need more time to find Ari Helenius' and Ucker's actual papers.)


PS eversion can be effectuated through a variety of mechanisms:

1. Viruses (Ari Helenius, ETH Hönggerberg, Switzerland)

Viruses interact with surface proteins to trigger macropinocytosis (EBS, this refers to the process of ingesting a virus-containing vesicle formed from the cell membrane that then enters the cell), and PS in the viral membrane can trigger this process.

The activation of surface proteins does not necessarily occur via direct interaction between PS in the viral membrane and proteins on the surface of host cells. [Adaptor proteins bridge some of these interactions.

My understanding, EBS, is that once the viral PS interacts with the adaptor proteins, it attaches to the cell membrane proteins, and then macropinocytoses into the cell, thereby triggering flippase to evert PS, suppressing the immune system, and ultimately "protecting" the invading virus from immune attack. This might very well explain how viruses maintain latency, i.e. they trigger PS eversion, thus enabling escape from weakened immune detection. (Very sneaky, IMO)


2. Glycolytic enzyme binding (David Ucker, Univ. of Illinois-Chicago)

The researchers showed both with proteomic studies and with assays that these glycolytic proteins are enriched on the surfaces of early apoptotic cells and that this externalization does not occur in viable cells. This process happens at the same time that PS externalization typically occurs.The externalization of glycolytic enzymes accounts for the binding of plasminogen to apoptotic cells. Caspase activity appears to be one of the triggers of this process because blocking caspase activity prevented the externalization of these enzymes.

What's the point? Well, when a cell is affected by either a virus or cancer, it's in trouble. It starts signaling that it's in trouble. Glycolytic enzymes on early apoptotic cells show that the cell is in trouble. And PS everts. (I believe this is how a virus such as Hepatitis C can lead to cirrhosis; it induces apoptosis with liver cells and "scars down" your liver i.e. "cirrhosis."

So there's my starting point. PS on viral cells and early apoptotic glycolytic enzymes that bind plasminogen signal the advent of PS eversion.

Best,

Joe