This gene found in gastric and bladder cancer is prognostic. Its amplification allows the cell to deal with austere conditions in Metastatic conditions. It seems to be amplifying under the impetus of HIF (Hypoxia induced factor). Its amplification appears more reactive than driving the resulting dowstream reaction.It can affect the structure of laminin and collagen through its formation of Aldehyde.
It can push proliferation by acting as a co-factor at nuclear level.
It can affect AKT (Protein Kinase B).
Recently, a study in Sarcoma using a Doxorubicin isoform was set in motion. Expression of LOX should be included in the analysis since Hypoxia was a component of the treatment.
LOX would not be a principal target in a treatment strategy since it addresses mostly metastasis, it either an adjunct treatment, or will have a role in Maintenance therapy.
Showing posts with label collagen. Show all posts
Showing posts with label collagen. Show all posts
Wednesday, March 27, 2013
Sunday, February 17, 2013
TTP
THROMBOTIC THROMBOCYTOPENIC PURPURA (HYPOTHESIS CONTINUES)
Here is the example of a metastatic mechanism going bad when it hits the right ADAM. Remember that ADAM are made of 2 basic domains, one an integrin and one a metalloproteinase domain. The Metalloproteinase enters the Flippase-floppase (or sometimes scramblase)-like structure and is destined to be rejected outside, the Integrin is sent inside the cell.
Metalloproteinases are sent outside and attack collagen-like molecules to open the way to cell migration and allow Metastatic processes to move forward. However, the cell membranes have a collagen-like structure, too. So potentially the released Metalloproteinases could attack the cell. The cell is not stupid and knows what metalloproteinase it has put out. So it shields itself with Inhibitors and Decoy receptors from that specific metalloproteinase and the cell goes about its migration.
2 conclusions:
1. Insufficient inhibitors and decoy receptors to Metalloproteinases (and others such as Hydroeicosatetraenoic Acid) will have devastating effects. If genetically the inhibitors are insufficient, and metalloproteinases are expressed massively, and this happens at the endothelial cell, massive and extensive destruction of endothelial cells throughout the body happens, exposing collagen like structures of the blood vessel walls. This of course trigger extensive activation of platelets and the Thrombosis of TTP-like syndrome. So in TTP, it is the inhibitor that is lacking. (ie Von Willebrand cleaving protease inhibitors have also been cited). And plasmapheresis removes the the Metalloproteinases (and microbial Antigens/toxin when relevent), stopping the onslaught.
2.What is in the Integrin domain is critical, in ADAM-17, the integrin domain is occupied by TNF-alpha, converting enzyme (TACE) which will free and activate the devastating Tumor Necrosis Factor. Released massively, TNF can not only induce Apoptosis like certain other Cyclins (interleukine and Interferon ), but also leads directly to NECROSIS. A massive uncontrolled septic-like syndrome kills rats after infusion of TNF.
ADAM 10, the disintegrin there gives you Amyloid structures of Alzheimer's. TO BE SHORT, PICK THE ADAM AND SEE THE CONSEQUENT DISEASE ON YOUR OWN!
ADAM! A FLIPPASE, FLOPPASE AND/OR A SCRAMBLASE-LIKE MOLECULE !
Here is the example of a metastatic mechanism going bad when it hits the right ADAM. Remember that ADAM are made of 2 basic domains, one an integrin and one a metalloproteinase domain. The Metalloproteinase enters the Flippase-floppase (or sometimes scramblase)-like structure and is destined to be rejected outside, the Integrin is sent inside the cell.
Metalloproteinases are sent outside and attack collagen-like molecules to open the way to cell migration and allow Metastatic processes to move forward. However, the cell membranes have a collagen-like structure, too. So potentially the released Metalloproteinases could attack the cell. The cell is not stupid and knows what metalloproteinase it has put out. So it shields itself with Inhibitors and Decoy receptors from that specific metalloproteinase and the cell goes about its migration.
2 conclusions:
1. Insufficient inhibitors and decoy receptors to Metalloproteinases (and others such as Hydroeicosatetraenoic Acid) will have devastating effects. If genetically the inhibitors are insufficient, and metalloproteinases are expressed massively, and this happens at the endothelial cell, massive and extensive destruction of endothelial cells throughout the body happens, exposing collagen like structures of the blood vessel walls. This of course trigger extensive activation of platelets and the Thrombosis of TTP-like syndrome. So in TTP, it is the inhibitor that is lacking. (ie Von Willebrand cleaving protease inhibitors have also been cited). And plasmapheresis removes the the Metalloproteinases (and microbial Antigens/toxin when relevent), stopping the onslaught.
2.What is in the Integrin domain is critical, in ADAM-17, the integrin domain is occupied by TNF-alpha, converting enzyme (TACE) which will free and activate the devastating Tumor Necrosis Factor. Released massively, TNF can not only induce Apoptosis like certain other Cyclins (interleukine and Interferon ), but also leads directly to NECROSIS. A massive uncontrolled septic-like syndrome kills rats after infusion of TNF.
ADAM 10, the disintegrin there gives you Amyloid structures of Alzheimer's. TO BE SHORT, PICK THE ADAM AND SEE THE CONSEQUENT DISEASE ON YOUR OWN!
ADAM! A FLIPPASE, FLOPPASE AND/OR A SCRAMBLASE-LIKE MOLECULE !
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