Abstract | PURPOSE: EXPERIMENTAL DESIGN: RESULTS: Hypoxic conditions increased phosphorylation of Akt and MAPK(Erk) and NF-kappa B DNA binding activity in L3.6pl cells. The activation of Akt and NF-kappa B was prevented by LY294002, whereas the activity of MAPK(Erk), but not NF-kappa B, was inhibited by U0126. The increased activation of Akt, NF-kappa B, and MAPK(Erk) was inhibited by PKI 166. Under hypoxic conditions, L3.6pl cells were resistant to apoptosis induced by gemcitabine. The addition of LY294002 or PKI 166 abrogated cell resistance to gemcitabine, whereas U0126 only partially decreased this resistance. CONCLUSIONS:
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Authors | Kenji Yokoi, Isaiah J Fidler |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 10
Issue 7
Pg. 2299-306
(Apr 01 2004)
ISSN: 1078-0432 [Print] United States |
PMID | 15073105
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antimetabolites, Antineoplastic
- Antineoplastic Agents
- Butadienes
- Chromones
- Enzyme Inhibitors
- Morpholines
- NF-kappa B
- Nitriles
- Pyrimidines
- Pyrroles
- Sp1 Transcription Factor
- U 0126
- Deoxycytidine
- 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
- Tyrosine
- Epidermal Growth Factor
- PKI 166
- Phosphatidylinositol 3-Kinases
- ErbB Receptors
- Protein-Tyrosine Kinases
- Mitogen-Activated Protein Kinases
- Oxygen
- Gemcitabine
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Topics |
- Antimetabolites, Antineoplastic
(pharmacology)
- Antineoplastic Agents
(pharmacology)
- Apoptosis
- Blotting, Western
- Butadienes
(pharmacology)
- Cell Division
- Cell Line, Tumor
- Chromones
(pharmacology)
- Deoxycytidine
(analogs & derivatives, pharmacology)
- Dose-Response Relationship, Drug
- Enzyme Inhibitors
(pharmacology)
- Epidermal Growth Factor
(metabolism)
- ErbB Receptors
(metabolism)
- Humans
- Hypoxia
- Mitogen-Activated Protein Kinases
(metabolism)
- Morpholines
(pharmacology)
- NF-kappa B
(metabolism)
- Neovascularization, Pathologic
- Nitriles
(pharmacology)
- Oxygen
(metabolism)
- Pancreatic Neoplasms
(metabolism, pathology)
- Phosphatidylinositol 3-Kinases
(metabolism)
- Phosphorylation
- Protein-Tyrosine Kinases
(antagonists & inhibitors)
- Pyrimidines
(pharmacology)
- Pyrroles
(pharmacology)
- Signal Transduction
- Sp1 Transcription Factor
(metabolism)
- Time Factors
- Tyrosine
(metabolism)
- Gemcitabine
|