You can not produce music or create on this level with RCC or renal cell carcinoma.
The tip for today is to consider praying for 3 things for people who do have this disease even if you do not
The tip for today is to consider praying for 3 things for people who do have this disease even if you do not
1. Th1 prototype (inducible by certain Amino Acids)
2. decreasing levels/HIF2a
3. Increasing Stat 2 activation by Il2
Hypoxia-inducible factor-2α: effect on radiation sensitivity and differential regulation by an mTOR inhibitor
Rupal S. Bhatt/Department of Medicine, *Division of Cancer Biology and Daniel M. Landis/†Department of Radiation Oncology, Swedish Cancer Institute, Seattle, WA, USAMichael Zimmer/‡Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital, MA, and Joelle Torregrossa/Department of Medicine, *Division of Cancer Biology and Shaoyong Chen/Department of Medicine, *Division of Cancer Biology and Vikas P. Sukhatme/§Nephrology, Beth Israel Deaconess Medical Center, Boston, Othon Iliopoulos/‡Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital, MA, and Steve Balk/Department of Medicine, *Division of Cancer Biology and Glenn J. BubleDepartment of Medicine, *Division of Cancer Biology and Glenn Bubley, Harvard Institute of Medicine, 77 Avenue Louis Pasteur, Boston, MA 02215, USA.e-mail: gbubley@bidmc.harvard.edu
· Department of Medicine, *Division of Cancer Biology and §Nephrology, Beth Israel Deaconess Medical Center, Boston, ‡Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital, MA, and †Department of Radiation Oncology, Swedish Cancer Institute, Seattle, WA, USA
Glenn Bubley, Harvard Institute of Medicine, 77 Avenue Louis Pasteur, Boston, MA 02215, USA.e-mail: gbubley@bidmc.harvard.edu
R.S.B. and D.M.L. contributed equally to this work
: HIF , hypoxia-inducible factor ; shRNA , short-hairpin RNA ; HRE , hypoxia responsive element ; VHL , von Hippel-Lindau tumour-suppressor gene.
OBJECTIVE
To determine the role of hypoxia-inducible factor-2α (HIF2α) on the sensitivity of renal cell carcinoma (RCC) cell lines to ionizing radiation and to determine if the mTOR antagonist, rapamycin, could decrease HIF2α protein levels.
MATERIALS AND METHODS
Cell lines expressing stable short-hairpin RNAs (shRNAs) encoding HIF2α shRNAs or an empty vector were transfected with a hypoxia responsive element (HRE)-driven firefly luciferase reporter gene. Two separate paired cell lines were assayed for their response to increasing doses of ionizing radiation. Proliferation and cell cycle kinetics were compared for cell lines expressing HIF2α shRNAs and empty vectors. The effect of an mTOR antagonist, rapamycin on HIF1α and HIF2α proteins levels was also assessed.
RESULTS
We confirmed that the 786-O RCC lines with stably integrated shRNAs against HIF2α had decreased activation of a plasmid with a HRE-driven firefly luciferase reporter gene. Lines from two separate cell clones with decreased HIF2α levels showed a significant increase in radiation sensitivity and an increase in G2 cell cycle arrest. Rapamycin, while effective in decreasing HIF1α protein levels, did not affect HIF2α levels in either of the RCC cell lines.
CONCLUSIONS
These results show that decreasing levels of HIF2α leads to an increased sensitivity to ionizing radiation. This finding may explain in part, the known resistance of RCC to radiation therapy. Although mTOR antagonists are approved for the treatment of RCC, these agents do not decrease HIF2α levels and therefore might not be effective in enhancing the radio-sensitivity of these tumours.
Initiator
Prod / Activ
Prod / Activ
Jnl / Vol / Pg
Author / Yr
Misc / Vol / Ed
RCC
TGF-B/CA
IL2/Stat-5 activation
CA res and clin onc/133/7/487
song,cheryn/jun,sun-young/07
TGF-beta suppressed/ Il-2-induced STAT5 activation /anti-TGF-beta /enhanced IL-2-induced STAT5
RCC
Th2 prototype
Cell Imm/150/114
Schoof, Deric/93
RCC
increasing levels/HIF2a
sensitivity to radiotherapy
Rupal S. Bhatt//Daniel M. Landis/Michael Zimmer/Joelle Torregrossa/Shaoyong Chen/Vikas P. Sukhatme/Othon Iliopoulos/Steve Balk/Glenn J. Buble/08
Lines from two separate cell clones with decreased HIF2a levels showed a significant increase in radiation sensitivity and an increase in G2 cell cycle arrest.
Initiator Prod / Activ Prod Increased / Activ decreased Jnl / Vol / Pg Author / Yr Misc / Vol / Ed
RCC TGF-B/CA IL2/Stat-5 activation CA res and clin onc/133/7/487 song,cheryn/jun,sun-young/07 TGF-beta suppressed/ Il-2-induced STAT5 activation /anti-TGF-beta /enhanced IL-2-induced STAT5
RCC / Th2 prototype / Cell Imm/150/114 Schoof, Deric/93 RCC increasing levels/HIF2a sensitivity to radiotherapy
Rupal S. Bhatt//Daniel M. Landis/Michael Zimmer/Joelle Torregrossa/Shaoyong Chen/Vikas P. Sukhatme/Othon Iliopoulos/Steve Balk/Glenn J. Buble/08
Lines from two separate cell clones with decreased HIF2a levels showed a significant increase in radiation sensitivity and an increase in G2 cell cycle arrest.
Hypoxia-inducible factor-2α: effect on radiation sensitivity and differential regulation by an mTOR inhibitor
Rupal S. Bhatt/Department of Medicine, *Division of Cancer Biology and Daniel M. Landis/†Department of Radiation Oncology, Swedish Cancer Institute, Seattle, WA, USAMichael Zimmer/‡Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital, MA, and Joelle Torregrossa/Department of Medicine, *Division of Cancer Biology and Shaoyong Chen/Department of Medicine, *Division of Cancer Biology and Vikas P. Sukhatme/§Nephrology, Beth Israel Deaconess Medical Center, Boston, Othon Iliopoulos/‡Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital, MA, and Steve Balk/Department of Medicine, *Division of Cancer Biology and Glenn J. BubleDepartment of Medicine, *Division of Cancer Biology and Glenn Bubley, Harvard Institute of Medicine, 77 Avenue Louis Pasteur, Boston, MA 02215, USA.e-mail: gbubley@bidmc.harvard.edu
· Department of Medicine, *Division of Cancer Biology and §Nephrology, Beth Israel Deaconess Medical Center, Boston, ‡Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital, MA, and †Department of Radiation Oncology, Swedish Cancer Institute, Seattle, WA, USA
Glenn Bubley, Harvard Institute of Medicine, 77 Avenue Louis Pasteur, Boston, MA 02215, USA.e-mail: gbubley@bidmc.harvard.edu
R.S.B. and D.M.L. contributed equally to this work
: HIF , hypoxia-inducible factor ; shRNA , short-hairpin RNA ; HRE , hypoxia responsive element ; VHL , von Hippel-Lindau tumour-suppressor gene.
OBJECTIVE
To determine the role of hypoxia-inducible factor-2α (HIF2α) on the sensitivity of renal cell carcinoma (RCC) cell lines to ionizing radiation and to determine if the mTOR antagonist, rapamycin, could decrease HIF2α protein levels.
MATERIALS AND METHODS
Cell lines expressing stable short-hairpin RNAs (shRNAs) encoding HIF2α shRNAs or an empty vector were transfected with a hypoxia responsive element (HRE)-driven firefly luciferase reporter gene. Two separate paired cell lines were assayed for their response to increasing doses of ionizing radiation. Proliferation and cell cycle kinetics were compared for cell lines expressing HIF2α shRNAs and empty vectors. The effect of an mTOR antagonist, rapamycin on HIF1α and HIF2α proteins levels was also assessed.
RESULTS
We confirmed that the 786-O RCC lines with stably integrated shRNAs against HIF2α had decreased activation of a plasmid with a HRE-driven firefly luciferase reporter gene. Lines from two separate cell clones with decreased HIF2α levels showed a significant increase in radiation sensitivity and an increase in G2 cell cycle arrest. Rapamycin, while effective in decreasing HIF1α protein levels, did not affect HIF2α levels in either of the RCC cell lines.
CONCLUSIONS
These results show that decreasing levels of HIF2α leads to an increased sensitivity to ionizing radiation. This finding may explain in part, the known resistance of RCC to radiation therapy. Although mTOR antagonists are approved for the treatment of RCC, these agents do not decrease HIF2α levels and therefore might not be effective in enhancing the radio-sensitivity of these tumours.
Initiator
Prod / Activ
Prod / Activ
Jnl / Vol / Pg
Author / Yr
Misc / Vol / Ed
RCC
TGF-B/CA
IL2/Stat-5 activation
CA res and clin onc/133/7/487
song,cheryn/jun,sun-young/07
TGF-beta suppressed/ Il-2-induced STAT5 activation /anti-TGF-beta /enhanced IL-2-induced STAT5
RCC
Th2 prototype
Cell Imm/150/114
Schoof, Deric/93
RCC
increasing levels/HIF2a
sensitivity to radiotherapy
Rupal S. Bhatt//Daniel M. Landis/Michael Zimmer/Joelle Torregrossa/Shaoyong Chen/Vikas P. Sukhatme/Othon Iliopoulos/Steve Balk/Glenn J. Buble/08
Lines from two separate cell clones with decreased HIF2a levels showed a significant increase in radiation sensitivity and an increase in G2 cell cycle arrest.
Initiator Prod / Activ Prod Increased / Activ decreased Jnl / Vol / Pg Author / Yr Misc / Vol / Ed
RCC TGF-B/CA IL2/Stat-5 activation CA res and clin onc/133/7/487 song,cheryn/jun,sun-young/07 TGF-beta suppressed/ Il-2-induced STAT5 activation /anti-TGF-beta /enhanced IL-2-induced STAT5
RCC / Th2 prototype / Cell Imm/150/114 Schoof, Deric/93 RCC increasing levels/HIF2a sensitivity to radiotherapy
Rupal S. Bhatt//Daniel M. Landis/Michael Zimmer/Joelle Torregrossa/Shaoyong Chen/Vikas P. Sukhatme/Othon Iliopoulos/Steve Balk/Glenn J. Buble/08
Lines from two separate cell clones with decreased HIF2a levels showed a significant increase in radiation sensitivity and an increase in G2 cell cycle arrest.
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