Tissue redox activity as a sensing platform for imaging of cancer based on nitroxide redox cycle

Zhelev, Zhivko; Aoki, Ichio; Gadjeva, V.; Nikolova, Biliana; Bakalova, Rumiana; Saga, Tsuneo

doi:10.1016/j.ejca.2012.10.026

Cited by 32 publications

(43 citation statements)

References 32 publications

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“…The different interpretations of the experimental data from the nitroxide-enhanced MRI studies that are published in the literature can be explained by several reasons: (i) the use of nitroxides with different cell-penetrating ability, place of retention, and excretion rate, (ii) the heterogeneity of the signal in different tissues (as a result of their different structure and metabolism), (iii) the heterogeneity of the signal in same tissue for different cell-penetrating nitroxide probes (as a result of their different pharmacokinetics), and (iv) the different analytic approaches (conclusions based on: rate of MRI signal decay, half-life of nitroxide-enhanced MRI signal, and intensity of nitroxide-enhanced MRI signal; refs. [19][20][21][22][23][24].…”

Section: Discussionmentioning

confidence: 99%

“…Any significant deviation from this reference value indicates a redox imbalance, such as the high-oxidative or reducing activity of cells, tissues, or physiologic fluids. In previous studies, we established that in cancer-bearing mammalian tissues, the intensity, duration, and t 1/2 values were completely different from the respective reference values and that this parameter is a valuable diagnostic marker for carcinogenesis (19)(20)(21).…”

Section: Translational Relevancementioning

confidence: 97%

“…Recently, we reported a noninvasive methodology for the estimation of TRA on intact mammals, allowing a differentiation of cancer development from normal (healthy) conditions (19)(20)(21). The method is based on the redox cycle of cell-penetrating nitroxide derivatives and their MRI and electron paramagnetic resonance (EPR) contrast properties, which make them useful molecular sensors for TRA (Fig.…”

Section: Introductionmentioning

confidence: 99%

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Tissue Redox Activity as a Hallmark of Carcinogenesis: From Early to Terminal Stages of Cancer

Bakalova

Zhelev

Aoki

et al. 2013

Clinical Cancer Research

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Purpose: The study aimed to clarify the dynamics of tissue redox activity (TRA) in cancer progression and assess the importance of this parameter for therapeutic strategies.Experimental Design: The experiments were carried out on brain tissues of neuroblastoma-bearing, glioma-bearing, and healthy mice. TRA was visualized in vivo by nitroxide-enhanced MRI on anesthetized animals or in vitro by electron paramagnetic resonance spectroscopy on isolated tissue specimens. Two biochemical parameters were analyzed in parallel: tissue total antioxidant capacity (TTAC) and plasma levels of matrix metalloproteinases (MMP).Results: In the early stage of cancer, the brain tissues were characterized by a shorter-lived MRI signal than that from healthy brains (indicating a higher reducing activity for the nitroxide radical), which was accompanied by an enhancement of TTAC and MMP9 plasma levels. In the terminal stage of cancer, tissues in both hemispheres were characterized by a longer-lived MRI signal than in healthy brains (indicating a high-oxidative activity) that was accompanied by a decrease in TTAC and an increase in the MMP2/MMP9 plasma levels. Cancer progression also affected the redox potential of tissues distant from the primary tumor locus (liver and lung). Their oxidative status increased in both stages of cancer.Conclusions: The study shows that tissue redox balance is very sensitive to the progression of cancer and can be used as a diagnostic marker of carcinogenesis. The study also suggests that the noncancerous tissues of a cancer-bearing organism are susceptible to oxidative damage and should be considered a therapeutic target.

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Section: Discussionmentioning

confidence: 99%

Section: Translational Relevancementioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Tissue Redox Activity as a Hallmark of Carcinogenesis: From Early to Terminal Stages of Cancer

Bakalova

Zhelev

Aoki

et al. 2013

Clinical Cancer Research

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“…Many types of cancer cells have increased levels of ROS due to defective mitochondrial electron-transport chain (ETC) [26][27][28]. ROS generated by mitochondria (mtROS) are directly produced due to 'leaky' transfer of electrons to molecular oxygen in the course of OXPHOS.…”

Section: Altered Ros Production In Cancer Cellsmentioning

confidence: 99%

“…Normal cells maintain redox homeostasis with low basal ROS levels and are furnished with antioxidant systems to tolerate exogenous oxidative stress. Cancer cells have an increased pro-oxidant status as compared to normal cells [26,27], and the imbalance between ROS generation and the ability of cells to scavenge these species contribute to a persistent oxidative stress of cancer cells. This pro-oxidant state generates a redox adaptation response by upregulating the antioxidant capacity to maintain ROS levels below the toxicity threshold.…”

Section: Targeting Cancer Cells By Ros-mediated Mechanismmentioning

confidence: 99%

Redox-active and Redox-silent Compounds: Synergistic Therapeutics in Cancer

Tomasetti¹,

Santarelli²,

Alleva³

et al. 2015

CMC

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Tumours exhibit higher basal levels of reactive oxygen species (ROS) and altered redox environment compared to normal cells. Excessive level of ROS can be toxic to these cells, thus they become more vulnerable to damage by further ROS insults induced by pharmacological agents. However, the upregulation of antioxidant capacity in adaptation to intrinsic oxidative stress in cancer cells can confer drug resistance. Therefore, abrogation of such drug-resistant mechanisms by redox modulation could have significant therapeutic implications. Many redox-modulating agents have been developed. The redox-active system epitomised by ascorbate-driven quinone redox cycling, and the group of redox-silent vitamin E analogues represented by α-tocopheryl succinate have been shown to induce selective cancer cell death in different types of cancer. These compounds synergistically act by destabilising organelles like mitochondria, unleashing their apoptogenic potential, which results in efficient death of malignant cells and suppression of tumour growth. Consistent with this notion, clinical trials that aim to examine the therapeutic performance of novel redox-modulating drugs in cancer patients are currently under way.

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Polyradical PROXYL/TEMPO‐Derived Amides: Synthesis, Physicochemical Studies, DFT Calculations, and Antimicrobial Activity

et al. 2017

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Tissue redox activity as a sensing platform for imaging of cancer based on nitroxide redox cycle

Cited by 32 publications

References 32 publications

Tissue Redox Activity as a Hallmark of Carcinogenesis: From Early to Terminal Stages of Cancer

Tissue Redox Activity as a Hallmark of Carcinogenesis: From Early to Terminal Stages of Cancer

Redox-active and Redox-silent Compounds: Synergistic Therapeutics in Cancer

Polyradical PROXYL/TEMPO‐Derived Amides: Synthesis, Physicochemical Studies, DFT Calculations, and Antimicrobial Activity

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