Replies to post #186397 on Avid Bioservices Inc (CDMO)

[horselover45]

I have to give you an A for your persistence to keep digging.

Just trying to bring the light of day to another gold mine in southern California.

Hopefully the next 30 days they start showing their wares.

[biopharm]

Dmitry Gabrilovich : Peregrine Pharmaceuticals KOL : ... hot from the press and wonder if Alison Stopek picks up on these findings....

Pertenece a: PubMed Central (PMC3 - NLM DTD)

Descripción: A major mechanism by which cancers escape control by the immune system is by blocking the differentiation of myeloid cells into dendritic cells (DCs), immunostimulatory cells that activate anti-tumor T cells. Tumor-dependent activation of signal transducer and activator of transcription 3 (STAT3) signaling in myeloid progenitor cells is thought to cause this block in their differentiation. In addition, a signaling pathway through protein kinase C ßII (PKCßII) is essential for the differentiation of myeloid cells into DCs. Here, we found in humans and mice that breast cancer cells substantially decreased the abundance of PKCßII in myeloid progenitor cells through a mechanism involving the enhanced activation of STAT3 signaling by soluble, tumor-derived factors (TDFs). STAT3 bound to previously undescribed negative regulatory elements within the promoter of PRKCB, which encodes PKCßII. We also found a previously undescribed counter-regulatory mechanism through which the activity of PKCßII inhibited tumor-dependent STAT3 signaling by decreasing the abundance of cell-surface receptors, such as cytokine and growth factor receptors, that are activated by TDFs. Together, these data suggest that a previously unrecognized crosstalk mechanism between the STAT3 and PKCßII signaling pathways provides the molecular basis for the tumor-induced blockade in the differentiation of myeloid cells, and suggest that enhancing PKCßII activity may be a therapeutic strategy to alleviate cancer-mediated suppression of the immune system.

Autor(es): Farren, Matthew R. - Carlson, Louise M. - Netherby, Colleen S. - Lindner, Inna - Li, Pui - Kai - Gabrilovich, Dmitry I. - Abrams, Scott I. - Lee, Kelvin P. -

Id.: 58917820

Idioma: English -

Versión: 1.0

Estado: Final

Palabras clave: Article -

Tipo de recurso: Text -

Tipo de Interactividad: Expositivo

Nivel de Interactividad: muy bajo

Audiencia: Estudiante - Profesor - Autor -

Estructura: Atomic

Coste: no

Copyright: sí

Requerimientos técnicos: Browser: Any -

Fecha de contribución: 19-ago-2014

Contacto:

Localización:


http://biblioteca.universia.net/html_bura/ficha/params/title/tumor-induced-stat3-signaling-in-myeloid-cells-impairs-dendritic-cell/id/58917820.html

[biopharm]

This involves phospholipid signaling in cell death pathways; nitric oxide(NO) interactions with cellular components including posttranslational modification of proteins and NO signaling...

NO signaling = Nitric Oxide signaling... and again, how will NO play a role in possibly some form of biomarker for detecting the amount of flipped PS ??

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Nitric Oxide Dissociates Lipid Oxidation from Apoptosis and Phosphatidylserine Externalization during Oxidative Stress†

James P. Fabisiak ,*‡
Vladimir A. Tyurin ,‡§
Yulia Y. Tyurina ,‡§
Andrey Sedlov ,‡
John S. Lazo ,? and
Valerian E. Kagan ‡?

Department of Environmental and Occupational Health, School of Public Health, RIDC Park, 260 Kappa Drive, University of Pittsburgh, Pittsburgh, Pennsylvania 15238, and Department of Pharmacology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261
Biochemistry, 2000, 39 (1), pp 127–138
DOI: 10.1021/bi9912544
Publication Date (Web): December 8, 1999
Copyright © 2000 American Chemical Society

Oxidative stress in biological membranes can regulate various aspects of apoptosis, including phosphatidylserine (PS) externalization. It is not known, however, if the targets for these effects are lipids or proteins. Nitric oxide (NO), a bifunctional modulator of apoptosis, has both antioxidant and prooxidant potential. We report here that the NO donor PAPANONOate completely protected all phospholipids, including PS, from oxidation in HL-60 cells treated with 2,2‘-azobis(2,4-dimethylisovaleronitrile) (AMVN), presumably via the ability of NO to react with lipid-derived peroxyl radicals and terminate the propagation of lipid peroxidation. PAPANONOate, however, had no effect on PS externalization or other markers of apoptosis following AMVN. Therefore, PS oxidation is not required for PS externalization during AMVN-induced apoptosis. PS externalization was accompanied by inhibition of aminophospholipid translocase (APT). NO potentiated AMVN inhibition of APT. Treatment with PAPANONOate alone produced modest (20%) inhibition of APT without PS externalization. NO did not reverse AMVN-induced oxidation of glutathione and protein thiols. We speculate that APT was sensitive to AMVN and/or NO via modification of protein thiols critical for functional activity. Therefore, the lipoprotective effects of NO were insufficient to prevent PS externalization and apoptosis following oxidative stress. Other targets such as protein thiols may be important redox-sensitive regulators of apoptosis initiation and execution. Thus, in the absence of significant peroxynitrite formation, NO's antioxidant effects are restricted to protection of lipids, while modification of protein substrates continues to occur.

http://pubs.acs.org/doi/abs/10.1021/bi9912544?journalCode=bichaw

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Interesting seeing that exhaled NO was actually used as an endpoint...

Twenty adult, polysensitized subjects with seasonal and perennial allergic rhinitis who chose to undergo allergen immunotherapy were enrolled. They were evaluated at baseline, and 4, 8, 12, 24, and 52 weeks later. Exhaled nitric oxide was reported as the mean of triplicate determinations.

http://www.ncbi.nlm.nih.gov/pubmed/23958488

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http://www.dermnetnz.org/pathology/nitric-oxide.html