Differential regulation of monocyte cytokine release by αV and β2 integrins that bind CD23:
- Edkins, Adrienne L, Borland, Gillian, Acharya, Mridu, Cogdell, Richard, Ozanne, Bradford W, Cushley, William
- Authors: Edkins, Adrienne L , Borland, Gillian , Acharya, Mridu , Cogdell, Richard , Ozanne, Bradford W , Cushley, William
- Date: 2012
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165153 , vital:41213 , DOI: 10.1111/j.1365-2567.2012.03576.x
- Description: The human soluble CD23 (sCD23) protein displays highly pleiotropic cytokine‐like activity. Monocytic cells express the sCD23‐binding integrins αVβ3, αVβ5, αMβ2 and αXβ2, but it is unclear which of these four integrins most acutely regulates sCD23‐driven cytokine release. The hypothesis that ligation of different sCD23‐binding integrins promoted release of distinct subsets of cytokines was tested. Lipopolysaccharide (LPS) and sCD23 promoted release of distinct groups of cytokines from the THP‐1 model cell line.
- Full Text:
- Authors: Edkins, Adrienne L , Borland, Gillian , Acharya, Mridu , Cogdell, Richard , Ozanne, Bradford W , Cushley, William
- Date: 2012
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165153 , vital:41213 , DOI: 10.1111/j.1365-2567.2012.03576.x
- Description: The human soluble CD23 (sCD23) protein displays highly pleiotropic cytokine‐like activity. Monocytic cells express the sCD23‐binding integrins αVβ3, αVβ5, αMβ2 and αXβ2, but it is unclear which of these four integrins most acutely regulates sCD23‐driven cytokine release. The hypothesis that ligation of different sCD23‐binding integrins promoted release of distinct subsets of cytokines was tested. Lipopolysaccharide (LPS) and sCD23 promoted release of distinct groups of cytokines from the THP‐1 model cell line.
- Full Text:
Quinones and halogenated monoterpenes of algal origin show anti-proliferative effects against breast cancer cells in vitro:
- de la Mare, Jo-Anne, Lawson, Jessica C, Chiwakata, Maynard T, Beukes, Denzil R, Blatch, Gregory L, Edkins, Adrienne L
- Authors: de la Mare, Jo-Anne , Lawson, Jessica C , Chiwakata, Maynard T , Beukes, Denzil R , Blatch, Gregory L , Edkins, Adrienne L
- Date: 2012
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165165 , vital:41214 , DOI: 10.1007/s10637-011-9788-0
- Description: Red and brown algae have been shown to produce a variety of compounds with chemotherapeutic potential. A recent report described the isolation of a range of novel polyhalogenated monoterpene compounds from the red algae Plocamium corallorhiza and Plocamium cornutum collected off the coast of South Africa, together with the previously described tetraprenylquinone, sargaquinoic acid (SQA), from the brown algae Sargassum heterophyllum. In our study, the algal compounds were screened for anti-proliferative activity against metastatic MDA-MB-231 breast cancer cells revealing that a number of compounds displayed anti-cancer activity with IC50 values in the micromolar range. A subset of the compounds was tested for differential toxicity in the MCF-7/MCF12A system and five of these, including sargaquinoic acid, were found to be at least three times more toxic to the breast cancer than the non-malignant cell line.
- Full Text:
- Authors: de la Mare, Jo-Anne , Lawson, Jessica C , Chiwakata, Maynard T , Beukes, Denzil R , Blatch, Gregory L , Edkins, Adrienne L
- Date: 2012
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165165 , vital:41214 , DOI: 10.1007/s10637-011-9788-0
- Description: Red and brown algae have been shown to produce a variety of compounds with chemotherapeutic potential. A recent report described the isolation of a range of novel polyhalogenated monoterpene compounds from the red algae Plocamium corallorhiza and Plocamium cornutum collected off the coast of South Africa, together with the previously described tetraprenylquinone, sargaquinoic acid (SQA), from the brown algae Sargassum heterophyllum. In our study, the algal compounds were screened for anti-proliferative activity against metastatic MDA-MB-231 breast cancer cells revealing that a number of compounds displayed anti-cancer activity with IC50 values in the micromolar range. A subset of the compounds was tested for differential toxicity in the MCF-7/MCF12A system and five of these, including sargaquinoic acid, were found to be at least three times more toxic to the breast cancer than the non-malignant cell line.
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STAT3 interacts directly with Hsp90:
- Prinsloo, Earl, Kramer, Adam H, Edkins, Adrienne L, Blatch, Gregory L
- Authors: Prinsloo, Earl , Kramer, Adam H , Edkins, Adrienne L , Blatch, Gregory L
- Date: 2012
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165142 , vital:41212 , DOI: 10.1002/iub.607
- Description: Heat shock protein 90 (Hsp90) functionally modulates signal transduction. The signal transducer and activator of transcription 3 (STAT3) mediates interleukin‐6 family cytokine signaling. Aberrant activation and mutation of STAT3 is associated with oncogenesis and immune disorders, respectively. Hsp90 and STAT3 have previously been shown to colocalize and coimmunoprecipitate in common complexes.
- Full Text:
- Authors: Prinsloo, Earl , Kramer, Adam H , Edkins, Adrienne L , Blatch, Gregory L
- Date: 2012
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/165142 , vital:41212 , DOI: 10.1002/iub.607
- Description: Heat shock protein 90 (Hsp90) functionally modulates signal transduction. The signal transducer and activator of transcription 3 (STAT3) mediates interleukin‐6 family cytokine signaling. Aberrant activation and mutation of STAT3 is associated with oncogenesis and immune disorders, respectively. Hsp90 and STAT3 have previously been shown to colocalize and coimmunoprecipitate in common complexes.
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Targeting conserved pathways as a strategy for novel drug development: disabling the cellular stress response:
- Edkins, Adrienne L, Blatch, Gregory L
- Authors: Edkins, Adrienne L , Blatch, Gregory L
- Date: 2012
- Language: English
- Type: text , book
- Identifier: http://hdl.handle.net/10962/165129 , vital:41211 , ISBN 978-3-642-28174-7 , DOI: 10.1007/978-3-642-28175-4_4
- Description: The ability to respond to and cope with stress at a molecular level is essential for cell survival. The stress response is conserved across organisms by the expression of a group of molecular chaperones known as heat shock proteins (HSP). HSP are ubiquitous and highly conserved proteins that regulate cellular protein homeostasis and trafficking under physiological and stressful conditions, including diseases such as cancer and malaria. HSP are good drug targets for the treatment of human diseases, as the significant functional and structural data available suggest that they are essential for cell survival and that, despite conservation across species, there are biophysical and biochemical differences between HSP in normal and disease states that allow HSP to be selectively targeted. In this chapter, we review the international status of this area of research and highlight progress by us and other African researchers towards the characterisation and targeting of HSP from humans and parasites from Plasmodium and Trypanosoma as drug targets.
- Full Text:
- Authors: Edkins, Adrienne L , Blatch, Gregory L
- Date: 2012
- Language: English
- Type: text , book
- Identifier: http://hdl.handle.net/10962/165129 , vital:41211 , ISBN 978-3-642-28174-7 , DOI: 10.1007/978-3-642-28175-4_4
- Description: The ability to respond to and cope with stress at a molecular level is essential for cell survival. The stress response is conserved across organisms by the expression of a group of molecular chaperones known as heat shock proteins (HSP). HSP are ubiquitous and highly conserved proteins that regulate cellular protein homeostasis and trafficking under physiological and stressful conditions, including diseases such as cancer and malaria. HSP are good drug targets for the treatment of human diseases, as the significant functional and structural data available suggest that they are essential for cell survival and that, despite conservation across species, there are biophysical and biochemical differences between HSP in normal and disease states that allow HSP to be selectively targeted. In this chapter, we review the international status of this area of research and highlight progress by us and other African researchers towards the characterisation and targeting of HSP from humans and parasites from Plasmodium and Trypanosoma as drug targets.
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