Hypoxia, drug therapy and toxicity

Lee, KangAe; Roth, Robert A.; LaPres, John J.

doi:10.1016/j.pharmthera.2006.08.001

Cited by 103 publications

(71 citation statements)

References 140 publications

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“…HIF-1a is constitutively synthesized and is degraded in an oxygen-dependent manner (103). Besides the aforementioned hypoxia and substrate-level stabilization by pyruvate and lactate, HIF proteins can be stabilized by multiple genetic factors, such as epidermal growth factor and insulin receptor activation, nitrous oxide, Akt (kinase B) activity, and ras/MEK activity (104)(105)(106)(107)(108)(109)(110)(111)(112)(113). Because of this, HIF can be characterized as being reversibly increased by physiologic stress (e.g., hypoxia) or by hormonal growth factor stimulation or as being constitutively active under normoxic conditions through heritable alterations, such as activated oncogenes.…”

Section: Hypoxia-inducible Factormentioning

confidence: 99%

Causes and Consequences of Increased Glucose Metabolism of Cancers

Gillies

Robey²,

Gatenby³

2008

J Nucl Med

559

482

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Section: Hypoxia-inducible Factormentioning

confidence: 99%

Causes and Consequences of Increased Glucose Metabolism of Cancers

Gillies

Robey²,

Gatenby³

2008

J Nucl Med

559

482

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“…Apoptosis was induced treating cells with Etoposide phosphate (VP-16) (50 µM) or Cis-Platinum (Cis-P) (25 µM) [7,17]. After drug treatment, either at 8, 16, 24 and 32 h or at different drug concentration (1,5,10,20,30 µM for 48 h), cells were collected by centrifugation at 1500 rpm for 5 min, washed twice with 100 µl of PBS and resuspended in 10 µl PBS for FT-IR analysis.…”

Section: Cell Growth and Apoptosismentioning

confidence: 99%

FT-IR spectromicroscopy of mammalian cell cultures during necrosis and apoptosis induced by drugs

Lamberti¹,

Sanges²,

Arcari

2010

Spectroscopy

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Abstract. FT-IR is used in the field of biology and medicine to detect bimolecular changes in disordered cells and tissues. In this report, using FT-IR microscopy, we characterize changes in apoptotic and necrotic Jurkat cells with respect to normal cells. The analysis of deconvoluted regions of the FT-IR spectra showed significant differences compared to the controls in three spectral regions. In particular, the apoptotic cells were characterized by an increase in the absorption at 2925 cm −1 , due to the asymmetric CH 2 -stretching (νasCH 2 ) of membrane lipids whereas the spectral areas ratio (A 1654 /A 1629 ) of the amide I region indicated an increase in apoptotic cells of more α-helical structures with respect to of β-sheet content. Interestingly, apoptotic cells showed the appearance of a peak around 1743 cm −1 , ν(C=O) assigned to acid ester. Because no other similar increase for lipid bands was observed, the increase of A 1745 is not simply due to an increase in the number of lipid molecules or their density but could also be indicative as marker of apoptosis. These spectral changes were not observed in necrotic Jurkat cells.

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“…In hypoxia, decreased proline hydroxylation causes HIF-1␣ to accumulate and translocate to the nucleus, where it binds to HIF-1␤, forming the transcriptionally competent HIF-1 that binds hypoxia response elements in DNA. HIF-regulated genes include plasminogen activator inhibitor-1 (PAI-1), vascular endothelial growth factor (VEGF), tumor necrosis factor ␣ (TNF␣), interleukin-1␤ (IL-1␤), and cell death proteins such as BNIP3 and Nix (Murdoch et al, 2005;Lee et al, 2007). HIF-1␣ expression and activation are also regulated by oxidative stress (Klimova and Chandel, 2008), inflammatory cytokines (Walmsley et al, 2005a), and thrombin (Görlach et al, 2001).…”

Section: Introductionmentioning

confidence: 99%