Oxidative stress therapy for solid tumors – A proposal

Undiminishing actuality of enzyme modification for therapeutic purposes has been confirmed by application of modified enzymes in clinical practice and numerous research data on them. Intravenous injection of the superoxide dismutase-chondroitin sulfate-catalase (SOD-CHS-CAT) conjugate in preventive and medicative regimes in rats with endotoxin shock induced with a lipopolysaccharide bolus has demonstrated that antioxidant agents not only effectively prevent damage caused by oxidative stress (as believed previously) but also can be used for antioxidative stress therapy. The results obtained emphasize the importance of investigation into the pathogenesis of vascular damage and the role of oxidative stress in it. The effects of intravenous medicative injection of SOD-CHS-CAT in a rat model of endotoxin shock have demonstrated a variety in the activity of this conjugate in addition to prevention of NO conversion in peroxynitrite upon interaction withO2∙-superoxide radical. Together with the literature data, these findings offer a prospect for the study of NO-independent therapeutic effects of SOD-CHS-CAT, implying the importance of a better insight into the mechanisms of the conjugate activity in modeled cardiovascular damage involving vasoactive agents other than NO.

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An NIR-II Responsive Nanoplatform for Cancer Photothermal and Oxidative Stress Therapy

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.751757 ◽

2021 ◽

Vol 9 ◽

Author(s):

Bin Huang ◽

Yuanpeng Huang ◽

Han Han ◽

Qiuyue Ge ◽

Dongliang Yang ◽

...

Keyword(s):

Oxidative Stress ◽

Photothermal Therapy ◽

Antitumor Effect ◽

Therapeutic Strategy ◽

Copper Ion ◽

Oxygen Species ◽

Intracellular Ros ◽

Stress Therapy ◽

Change Material ◽

And Oxidative Stress

Chemodynamic therapy as an emerging therapeutic strategy has been implemented for oncotherapy. However, the reactive oxygen species can be counteracted by the exorbitant glutathione (GSH) produced by the tumor cells before exerting the antitumor effect. Herein, borneol (NB) serving as a monoterpenoid sensitizer, and copper sulfide (CuS NPs) as an NIR-II photothermal agent were loaded in a thermo-responsive vehicle (NB/CuS@PCM NPs). Under 1,060-nm laser irradiation, the hyperthermia produced by CuS NPs can be used for photothermal therapy and melt the phase change material for drug delivery. In the acidity microenvironment, the CuS NPs released from NB/CuS@PCM NPs could degrade to Cu2+, then Cu2+ was reduced to Cu+ during the depletion of GSH. As Fenton-like catalyst, the copper ion could convert hydrogen peroxide into hydroxyl radicals for chemodynamic therapy. Moreover, the NB originated from NB/CuS@PCM NPs could increase the intracellular ROS content to improve the treatment outcome of chemodynamic therapy. The animal experimental results indicated that the NB/CuS@PCM NPs could accumulate at the tumor site and exhibit an excellent antitumor effect. This work confirmed that the combination of oxidative stress–induced damage and photothermal therapy is a potential therapeutic strategy for cancer treatment.

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Oxidative Stress Therapy for Cancer Using Glycolysis Inhibitors: Towards Improving Therapeutic Outcomes

American Journal of Medical and Biological Research ◽

10.12691/ajmbr-6-1-3 ◽

2018 ◽

Vol 6 (1) ◽

pp. 11-15

Author(s):

Salah Mohamed El Sayed

Keyword(s):

Oxidative Stress ◽

Therapeutic Outcomes ◽

Glycolysis Inhibitors ◽

Stress Therapy

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Prognostic Role of the Activated p-AKT Molecule in Various Hematologic Malignancies and Solid Tumors: A Meta-Analysis

Frontiers in Oncology ◽

10.3389/fonc.2020.588200 ◽

2020 ◽

Vol 10 ◽

Author(s):

Zhen Yao ◽

Guangyu Gao ◽

Jiawen Yang ◽

Yuming Long ◽

Zhenzhen Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Cancer Patients ◽

Solid Tumors ◽

Meta Analysis ◽

Hematologic Malignancies ◽

Prognostic Role ◽

Phosphorylated Akt ◽

Comprehensive Search ◽

Hematological Tumor

Cancer is one of the main causes of human death worldwide. Recently, many studies have firmly established the causal relationship between oxidative stress and cancer initiation and progression. As a key protein in PI3K/Akt signaling pathway, p-AKT (phosphorylated Akt) participates in the process of oxidative stress and plays a prognostic role in various hematologic tumors and solid tumors. We conducted a comprehensive search of the PubMed, Embase and Cochrane libraries to identify studies published in the past decade involving cancer patients expressing p-AKT that reported overall survival (OS) during follow-up. In this study, 6,128 patients in total were evaluated from 29 enrolled articles, and we concluded that overexpression of p-AKT was closely related to worse OS in cancer patients with a hazard ratio (HR) of 2.33 (95% CI: 1.67–4.00). Furthermore, we conducted a subgroup analysis, and the results indicated that overexpression of p-AKT was associated with worse OS in hematological tumor (HR: 1.64, 95% CI: 1.41–1.92), and solid tumor (HR: 2.44, 95% CI: 1.61–5.26). High expression of p-AKT is related to poor prognosis of various hematologic tumors and solid tumors.

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Attenuation of Oxidative Stress by Cannabinoids and Cannabis Extracts in Differentiated Neuronal Cells

Pharmaceuticals ◽

10.3390/ph13110328 ◽

2020 ◽

Vol 13 (11) ◽

pp. 328

Author(s):

Aruna Raja ◽

Soha Ahmadi ◽

Fernanda de Costa ◽

Nan Li ◽

Kagan Kerman

Keyword(s):

Oxidative Stress ◽

Antioxidant Activity ◽

Neuronal Cells ◽

In Vitro Models ◽

Proof Of Concept ◽

In Vitro System ◽

Pathological Conditions ◽

Stress Therapy ◽

Antagonist Effect

In this proof-of-concept study, the antioxidant activity of phytocannabinoids, namely cannabidiol (CBD) and Δ9- tetrahydrocannabinol (THC), were investigated using an in vitro system of differentiated human neuronal SY-SH5Y cells. The oxidative stress was induced by hydrogen peroxide, as reactive oxygen species (ROS). Alzheimer’s disease (AD)-like pathological conditions were mimicked in vitro by treating the differentiated neuronal cells with amyloid-β1–42 (Aβ1–42) in the presence of Cu(II). We showed that THC had a high potency to combat oxidative stress in both in vitro models, while CBD did not show a remarkable antioxidant activity. The cannabis extracts also exhibited a significant antioxidant activity, which depended on the ratio of the THC and CBD. However, our results did not suggest any antagonist effect of the CBD on the antioxidant activity of THC. The effect of cannabis extracts on the cell viability of differentiated human neuronal SY-SH5Y cells was also investigated, which emphasized the differences between the bioactivity of cannabis extracts due to their composition. Our preliminary results demonstrated that cannabis extracts and phytocannabinoids have a promising potential as antioxidants, which can be further investigated to develop novel pharmaceuticals targeting oxidative stress therapy.

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Amplified Oxidative Stress Therapy of Degradable Copper Phosphate Nanozyme Coated by in situ Polymerization of PEGDA

Journal of Materials Chemistry B ◽

10.1039/d1tb00436k ◽

2021 ◽

Author(s):

Ning Nie ◽

Yifan Liu ◽

Bing Li ◽

Zhentao Hua ◽

Jianfeng Liu ◽

...

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

In Situ Polymerization ◽

Reactive Oxygen ◽

Oxygen Species ◽

First Report ◽

Copper Phosphate ◽

Stress Therapy

Elimination of reactive oxygen species (ROS) caused by glutathione (GSH) is a fundamental concern in oxidative stress therapy (OST) of tumors. This is the first report of copper phosphate nanospheres...

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DNA Damage during Reoxygenation Elicits a Chk2-Dependent Checkpoint Response

Molecular and Cellular Biology ◽

10.1128/mcb.26.5.1598-1609.2006 ◽

2006 ◽

Vol 26 (5) ◽

pp. 1598-1609 ◽

Cited By ~ 44

Author(s):

Rachel A. Freiberg ◽

Ester M. Hammond ◽

Mary Jo Dorie ◽

Scott M. Welford ◽

Amato J. Giaccia

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Tumor Cell ◽

Solid Tumors ◽

Ataxia Telangiectasia ◽

Clonogenic Survival ◽

Ataxia Telangiectasia Mutated ◽

Checkpoint Response ◽

Opening And Closing ◽

And Oxidative Stress

ABSTRACT Due to the abnormal vasculature of solid tumors, tumor cell oxygenation can change rapidly with the opening and closing of blood vessels, leading to the activation of both hypoxic response pathways and oxidative stress pathways upon reoxygenation. Here, we report that ataxia telangiectasia mutated-dependent phosphorylation and activation of Chk2 occur in the absence of DNA damage during hypoxia and are maintained during reoxygenation in response to DNA damage. Our studies involving oxidative damage show that Chk2 is required for G2 arrest. Following exposure to both hypoxia and reoxygenation, Chk2−/− cells exhibit an attenuated G2 arrest, increased apoptosis, reduced clonogenic survival, and deficient phosphorylation of downstream targets. These studies indicate that the combination of hypoxia and reoxygenation results in a G2 checkpoint response that is dependent on the tumor suppressor Chk2 and that this checkpoint response is essential for tumor cell adaptation to changes that result from the cycling nature of hypoxia and reoxygenation found in solid tumors.

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Development of a novel oxidative stress-amplifying nanocomposite capable of supplying intratumoral H2O2 and O2 for enhanced chemodynamic therapy and radiotherapy in patient-derived xenograft (PDX) models

Nanoscale ◽

10.1039/d0nr06594c ◽

2020 ◽

Vol 12 (45) ◽

pp. 23259-23265

Author(s):

Meng Suo ◽

Zeming Liu ◽

Wenxue Tang ◽

Jiancheng Guo ◽

Wei Jiang ◽

...

Keyword(s):

Oxidative Stress ◽

Antioxidant Enzymes ◽

Tumor Microenvironment ◽

Cancer Treatment ◽

Solid Tumors ◽

Patient Derived Xenograft ◽

Pdx Models

Radiotherapy (RT) is a potent approach to cancer treatment, but the tumor microenvironment (TME) in solid tumors is often highly hypoxic and contains high levels of antioxidant enzymes, thereby reducing the RT efficacy.

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