Role of Avastin-Anti-JAK2 and Anti-c-MET in Metastatic triple negative and possibly inflammatory Breast Cancer
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OF NOTE, for you to continue following:
" CTGF, also known as CCN2 or connective tissue growth factor,[1][2] is a matricellular protein of the CCN family of extracellular matrix-associated heparin-binding proteins (see also CCN intercellular signaling protein).[3][4][5] CTGF has important roles in many biological processes, including cell adhesion, migration, proliferation, angiogenesis, skeletal development, and tissue wound repair, and is critically involved in fibrotic disease and several forms of cancers.[1][2][6wikipedia.
Members of the CCN protein family, including CTGF, are structurally characterized by having four conserved, cysteine residue-rich domains, and these domains are, from N- to C-termini, the insulin-like growth factor binding protein (IGFBP) domain, von Willebrand type C repeats (vWC) domain, the thrombospondin type 1 repeat (TSR) domain, and a C-terminal domain (CT) with a cysteine knot motif. CTGF mediates its functions through binding to various cell surface receptors in a context-dependent manner, including integrin receptors,[7][8][9] cell surface heparan sulfate proteoglycans (HSPGs),[10] LRPs,[11] and TrkA.[12] In addition, CTGF also binds growth factors and extracellular matrix proteins. The N-terminal half of CTGF interacts with aggrecan,[13] the TSR domain interacts with VEGF,[14] and the CT domain interacts with members of the TGF-β superfamily, fibronectin, perlecan, fibulin-1, slit, and mucins.["wikipedia
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TNF, INTERFERON alpha, JAK-2,CNN2.
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According to Schultz,
TNF alpha potentiates the negative influence of Intereferon-alpha on CCN proteins. "the CCN proteins are known to be involved in the development, homeostasis, and repair of mesenchymal cells", to which breast cancer cells belong. WISP3/CCN6, incriminated in the Inflammatory Breast Cancer, member of the Wnt1.
In fact WISP3 has "growth and angiogenesis inhibitory functions" (ASCO).
Should interferon alpha knocks down the WISP3, "overexpression of the epithelial adhesion molecule protein E-Cadherin, overexpression of RhoC oncogene, and high frequency of p53 gene Mutations could result as seen in inflammatory Breast cancers!
now the statement that follows has deep meaning (careful now!)
"The inhibitory effect of Interferon-gamma on CTGF could almost be completely compensated by JAK-2 inhibitor AG-409". This implies that the "CTGF expression is negatively regulated by the JAK/STAT signaling pathway in a independant manner". This suggests that a JAK-2 Inhibitor could stop part on the neoplastic transformation, and play a therapeutic role!
ROLE OF AVASTIN
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another CCN1/CYR61 has angiogenic function which it assumes by binding to an Integrin (Alpha-v-Beta1) of endothelial cells. CYR6 promotes proliferation, migration and adhesion and survival. It also enhances Cytotoxicity of TNF alpha on fibroblasts. CYR61 gene expression is induced by the WNT3A. Bringing further the Wnt pathway into the mix.
(Leap to Autoimmune disease)
The overexpression of the WISP3 inhibit BMP and the Wnt signaling. It has been found Upregulated in Rheumatoid arthritis. It could indeed serve as a bio-marker !
Wisp3/CCN6 controls Homeostasis as stated above. It has been reported that the overexpression of WISP3 increase the activities of the SuperOxide Dismutase, a cell anti-Oxidant that palys a protective role. And therefore decrease of WISP3, may heavily play into the the neoplastic process!
Furthermore, Mutation or suppression of WISP3 increases VEGF, affects cell growth, and impact neoplastic angiogenesis and cancerous invasion of tissues! Wisp3 cell metastasis is driven through its attachment to Integrin AvB5. "a potential target for therapy! (there you have it thanks to all researchers who got there before us!)
THE CRBCM IS WORKING HARD TOWARD THE CURE...AND WILL NOT BE DISTRACTED BY POLITICS THAT " FLORISH" IN FUNDING INSTITUTIONS IN TEXAS, NIH AND ELSEWHERE...HELL WE ARE CURRENTLY FUNDING OUR OWN RESEARCH WITH THE HELP OF GREATER EAST CANCER CENTER! WE WILL GET THERE FOLLOWING OUR OWN SNIFF!
OF NOTE
When somebody shows unnecessary signs of rudeness, grumpiness or stubbornness. Over competitiveness is also a symptom of florish behavior and they .....
www.merriam-webster.com/dictionary/sniff
to
take air into your nose in short breaths that are loud enough to be
heard. : to smell (something or someone) by putting your nose close to
it and taking air in ...
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