Replies to post #154134 on Avid Bioservices Inc (CDMO)

[biopharm]

The 4TH International Conference on Notch Targeting in Cancer
Date: June 25-27, 2014
Venue: Santa Marina Hotel, Mykonos, Greece

The fourth annual international conference devoted to Notch Biology and related Cancer Therapeutics will include basic and translational research, preclinical and clinical studies,
biomarker discovery and progress achieved thus far in this emerging and exciting field of targeting Notch, as examined and presented by leading scientists in the
field. Examples of speakers and preliminary topics include:

Dmitry Gabrilovich, The Wistar Institute, USA:

Effects of Notch Signaling on Regulation of Myeloid Cell
Differentiation in Cancer

http://www.cancerconferences.org/annual_meetings/PRELIMINARY-ANNOUNCEMENT-2014-conferences.pdf

I believe that the change in "Notch Signaling" does have a direct tie towards how Bavi targets "flipped-PS" ... but am trying to determine and look for "exact" wording from Dr. Dmitry Gabrilovich, though I need one of the more scientific minds to look at this possibly? It looks to me like Dr. Gabrilovich is increasing the awareness of how vital "targeting flipped-PS" actually may be.... but referring to "Notch" signaling... ? I could be wrong...

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Inhibition of Notch signaling was caused by the disruption of the interaction between Notch receptor and transcriptional repressor CSL, which is normally required for efficient transcription of target genes. This disruption was the result of serine phosphorylation of Notch. We demonstrated that increased activity of casein kinase 2 (CK2) observed in HPC and in MDSC could be responsible for the phosphorylation of Notch and downregulation of Notch signaling. Inhibition of CK2 by siRNA or by pharmacological inhibitor restored Notch signaling in myeloid cells and substantially improved their differentiation, both in vitro and in vivo. This study demonstrates a novel mechanism regulation of Notch signaling in cancer. This may suggest a new perspective for pharmacological regulation of differentiation of myeloid cells in cancer.

http://yourcancer.info/cancer-types/thyroid-cancer/notch-and-myeloid-cells-in-cancer/

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1) Dr. Dmetri Gabrilovich is in Mykonos on June 25-27 speaking on "Noth Targeting in Cancer"...

2) the section above I highlighted in red "Inhibition of CK2 by siRNA or by pharmacological inhibitor" ..... IS THIS "Pharmacological inhibitor" ?? possibly end up being the targeting of flipped-PS by Bavituximab ??? in other words.... is Dr. Dmitry Gabrilovich silently hinting at the powers of Bavi, though from another angle for the medical community to understand?

3) I bring this up as I read this section below from Wiki...and take note of the "..hundreds of such antibodies are now available" but Bavituximab is the one that targets "flipped-PS", which just may be considered the breakthrough discovery of all cancer resesarch... and gives some chance that a last minute buyout offer could come when many others do determine this to be true and accepted .... "and" put to practice.

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Detection and characterization

Antibodies can be used as powerful tools to detect whether a protein is phosphorylated at a particular site. Antibodies bind to and detect phosphorylation-induced conformational changes in the protein. Such antibodies are called phospho-specific antibodies; hundreds of such antibodies are now available.[20] They are becoming critical reagents both for basic research and for clinical diagnosis.

http://en.wikipedia.org/wiki/Phosphorylation

[biopharm]

The 4TH International Conference on Notch Targeting in Cancer
Date: June 25-27, 2014
Venue: Santa Marina Hotel, Mykonos, Greece

The fourth annual international conference devoted to Notch Biology and related Cancer Therapeutics will include basic and translational research, preclinical and clinical studies, biomarker discovery and progress achieved thus far in this emerging and exciting field of targeting Notch, as examined and presented by leading scientists in the
field. Examples of speakers and preliminary topics include:

Dmitry Gabrilovich, The Wistar Institute, USA:

Effects of Notch Signaling on Regulation of Myeloid Cell
Differentiation in Cancer

I'll be hammering away at Notch Signaling more, ever since the FDA confirmed blood tests in their latest guidance.... but lets take this in a little different direction = Atopic Dermatitis --aka---> Eczema:

Atopic dermatitis (eczema) is an itchy inflammation of your skin. It's a long-lasting (chronic) condition that may be accompanied by asthma or hay fever.

Eczema may affect any area of your skin, but it typically appears on your arms and behind your knees. It tends to flare periodically and then subside. The cause of atopic dermatitis is unknown, but it may result from a combination of inherited tendencies for sensitive skin and malfunction in the body's immune system.

http://www.mayoclinic.org/diseases-conditions/eczema/basics/definition/con-20032073

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Author Information

Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabrück, Osnabrück, Germany

* Correspondence:
Bodo C. Melnik, MD,
Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabrück, Sedanstrasse 115, D-49090 Osnabrück, Germany,
Tel.: [phone], Fax: [phone], e-mail: [e-mail]

Abstract

This viewpoint presents a unifying concept for the treatment of atopic dermatitis (AD) that is based on the improvement of deficient Notch signaling, which appears to represent the fundamental epithelial defect of AD resulting in epidermal and immunological barrier dysfunction. One study of AD patients demonstrated a marked epidermal deficiency of Notch receptors and several mouse models with genetically suppressed Notch signaling exhibit dry skin, signs of scratching, skin barrier abnormalities, increased transepidermal water loss and Th2 cell-mediated immunological changes closely resembling human AD. Notch signaling is critically involved in the differentiation of regulatory T cells, in the feedback inhibition of activated innate immunity, in the repression of activating protein-1 (AP-1), the regulation of late epidermal differentiation associated with filaggrin- and stratum corneum barrier lipid processing, in aquaporin 3- and claudin-1 expression and in keratinocyte-mediated release of thymic stromal lymphopoietin (TSLP), which promotes Th2-driven immune responses with TSLP- and IL-31-mediated stimulation of cutaneous sensory neurons involved in the induction of itch. Translational evidence will be provided that all major therapeutic regiments employed for the treatment of AD such as glucocorticoids, calcineurin inhibitors and UV radiation may converge in the upregulation of impaired Notch signaling, the proposed pathogenic defect of AD.

http://onlinelibrary.wiley.com/doi/10.1111/exd.12460/abstract

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Dr. Bodo Melnik:
http://www.researchgate.net/profile/Bodo_Melnik

one side note regarding linkedin PAV lists-- it looks like Dr. Bodo has one connection: A Director of Dermatology in Spain and by the rather large number of sites that "SunRise" has just officially started recruiting.... I'd say Spain may have an interest in Bavi..

http://es.linkedin.com/pub/luis-puig/27/86/768/en

....also, one of Dr. Bodo's top co-authors we have Dr. Stephen Grabbe: notice the Feb 2014 date.... lots of MDSC talk going on lately early in 2014 and thank goodness Peregrine has KOL Dr. Dmitry Gabrilovich who is probably the leading, global expert on such matters!

Article
Increased frequencies of CD11b(+) CD33(+) CD14(+) HLA-DR(low) myeloid derived suppressor cells are an early event in melanoma patients.

Berenice M Rudolph, Carmen Loquai, Alexander Gerwe, Nicole Bacher, Kerstin Steinbrink, Stephan Grabbe, Andrea Tuettenberg
Experimental Dermatology (Impact Factor: 3.58). 02/2014; DOI:10.1111/exd.12336
Source: PubMed

ABSTRACT

Myeloid-derived suppressor cells (MDSC) are a heterogeneous cell population characterized by immunosuppressive activity. Elevated levels of MDSC in peripheral blood are found in inflammatory diseases as well as in malignant tumors where they are supposed to be major contributors to mechanisms of tumor-associated tolerance. We investigated the frequency and function of MDSC in peripheral blood of melanoma patients and observed an accumulation of CD11b(+) CD33(+) CD14(+) HLA-DR(low) MDSC in all stages of disease (I-IV), including early stage I patients. Disease progression and enhanced tumor burden did not result in a further increase of frequencies or change in phenotype of MDSC. By investigation of specific MDSC-associated cytokines in patients' sera, we found an accumulation of IL-8 in all stages of disease. T cell suppressor assays revealed that MDSC critically contribute to suppressed antigen-specific T cell reactivity and thus might explain the frequently observed transient effects of immunotherapeutic strategies in melanoma patients.

http://www.researchgate.net/publication/260092756_Increased_frequencies_of_CD11b%28%29_CD33%28%29_CD14%28%29_HLA-DR%28low%29_myeloid_derived_suppressor_cells_are_an_early_event_in_melanoma_patients

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not sure about you... but this continues to become bigger than big and we've already heard/seen from Dr. Brekken the signs of where its all going and its becoming every soo clear that the MD of MDSC's: Dr. Dmitry Gabrilovich is heading to Mykonos in June to place some final nails in the coffin regarding the how and why MDSC's are ever so important and a blood test can easily determine this !

lets go Hypi... keep that stock price down just one more day : )
I am about to become greedy. Selling my spare lawnmower for more PPHM... what the hell