Dose-biomarker-response modeling of the anticancer effect of ethaselen in a human non-small cell lung cancer xenograft mouse model

Ye, Suofu; Li, Jian; Ji, Shuangmin; Lu, Wei

doi:10.1038/aps.2016.114

Cited by 17 publications

(9 citation statements)

References 40 publications

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“…After the inoculation of lung cancer cell, A549 from the left ventricle (17), severe systemic failure, shortness of breath and a 20% weight loss in nude mice indicate that the mice have had cachexia. Nude mice were injected intraperitoneally with 50mg/kg of 1% thiopental sodium for nude mice (18) (Shanghai Xiyuan Biotechnology Co. Ltd., article number: XY-EP-T1200000).…”

Section: Animal Imaging Testmentioning

confidence: 99%

Comparison of diagnostic efficacy of MRI and PET/CT in lung cancer of mouse with spinal metastasis

Liu

Xiao

et al. 2020

Cell Mol Biol (Noisy-le-grand)

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This study aimed to compare the diagnostic efficacy of MRI and PET/CT in lung cancer of mouse with spinal metastasis. 40 healthy Balb/c nude mice were selected. 0.1 ml of human lung cancer cell A549 bacterial suspension was injected by the left ventricle injection method to establish a lung cancer spinal metastasis model, and the abnormal signs of the nude mice were closely observed. When the body weight was reduced by 20%, micro PET/CT imaging and small coil MRI imaging were applied after intraperitoneal injection of thiopental anesthesia in nude mice. After the imaging was completed, the nude mouse was dissected and the spinal tumor was removed. The nature of spinal metastases was diagnosed by the pathology department. 5 nude mice died of abdominal infection, 2 nude mice had no spinal tumors, and the remaining 33 nude mice were successfully modeled. 33 nude mice were confirmed by pathology to have 64 metastatic vertebral lesions, among them, there were 7 cervical vertebrae, 24 thoracic vertebrae, 16 lumbar vertebrae, 6 sacral vertebrae and 11 caudal vertebrae. The sensitivity of MRI in the diagnosis of spinal metastases was 78.13%, and specificity was 56.25%. The sensitivity of PET/CT for the diagnosis of spinal metastases was 92.19%, and specificity was 78.95%. The specificity and positive predictive value of PET/CT for the diagnosis of spinal metastases were not significantly different from those of MRI (P> 0.05). The sensitivity, accuracy and negative predictive values were significantly higher than those of MRI (P< 0.05). PET/CT is superior to MRI in the diagnosis of spinal metastases, and its sensitivity, accuracy and negative predictive values were significantly higher than those of MRI (P< 0.05). It is worthy to be further promoted in clinical practice.

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Section: Animal Imaging Testmentioning

confidence: 99%

Comparison of diagnostic efficacy of MRI and PET/CT in lung cancer of mouse with spinal metastasis

Liu

Xiao

et al. 2020

Cell Mol Biol (Noisy-le-grand)

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“…Besides, ethaselen, an ebselen derivative, is in the recruiting phase of a clinical trial to treat lung cancer. The compound has been effective in a pre-clinical trial in human non-small cell lung cancer models (Ye et al 2017 ; Zheng et al 2017b , 2019b ). In short, though ebselen has not been approved to treat a specific disease, its safety in humans has been an indication that organoselenium compounds can be promising therapeutic agents.…”

Section: Introductionmentioning

confidence: 99%

Toxicology and pharmacology of synthetic organoselenium compounds: an update

2021

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Here, we addressed the pharmacology and toxicology of synthetic organoselenium compounds and some naturally occurring organoselenium amino acids. The use of selenium as a tool in organic synthesis and as a pharmacological agent goes back to the middle of the nineteenth and the beginning of the twentieth centuries. The rediscovery of ebselen and its investigation in clinical trials have motivated the search for new organoselenium molecules with pharmacological properties. Although ebselen and diselenides have some overlapping pharmacological properties, their molecular targets are not identical. However, they have similar anti-inflammatory and antioxidant activities, possibly, via activation of transcription factors, regulating the expression of antioxidant genes. In short, our knowledge about the pharmacological properties of simple organoselenium compounds is still elusive. However, contrary to our early expectations that they could imitate selenoproteins, organoselenium compounds seem to have non-specific modulatory activation of antioxidant pathways and specific inhibitory effects in some thiol-containing proteins. The thiol-oxidizing properties of organoselenium compounds are considered the molecular basis of their chronic toxicity; however, the acute use of organoselenium compounds as inhibitors of specific thiol-containing enzymes can be of therapeutic significance. In summary, the outcomes of the clinical trials of ebselen as a mimetic of lithium or as an inhibitor of SARS-CoV-2 proteases will be important to the field of organoselenium synthesis. The development of computational techniques that could predict rational modifications in the structure of organoselenium compounds to increase their specificity is required to construct a library of thiol-modifying agents with selectivity toward specific target proteins.

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“…These observations have been confirmed in different tumor cell lines including HeLa (human cervical cancer), BGC823 (human stomach adenocarcinoma), HL60 and K562 (human leukemia), A549 (human lung cancer), LoVo (human colon cancer), Bel-7402 (human epithelial hepatoma), Tca8113 (human tongue cancer), and KB (human nasopharyngeal epidermal carcinoma) cells, as well as in a human non-small-cell lung cancer xenograft mouse model. 30 Moreover, combination of BBSKE with sodium selenite in non-small-cell lung cancer cells 31 or with sunitinib 32 in colorectal cancer showed synergistic effects, resulting in a promising new strategy for cancer therapy. In addition, this derivative is able to reverse cisplatin resistance in drug-resistant K562 cells.…”

Section: 2-selenazolesmentioning

confidence: 99%

Development and Therapeutic Potential of Selenazo Compounds

et al. 2019

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Incorporation of selenium (Se) atom into small molecules can substantially enhance their antioxidant, antiinflammatory, antimutagenic, antitumoral or chemopreventive, antiviral, antibacterial, antifungal, antiparasitic, and neuroprotective effects. Specifically, selenazo compounds have received great attention owing to their chemical properties, pharmaceutical applications, and low toxicity. In this Perspective, we compile extensive literature evidence with the description and discussion of the most recent advances in different selenazo and selenadiazo motifs as potential pharmacological candidates. We also provide some perspectives on the challenges and future directions in the advancement of these selenazo compounds, each of which could generate drug candidates for various diseases.

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Dose-biomarker-response modeling of the anticancer effect of ethaselen in a human non-small cell lung cancer xenograft mouse model

Cited by 17 publications

References 40 publications

Comparison of diagnostic efficacy of MRI and PET/CT in lung cancer of mouse with spinal metastasis

Comparison of diagnostic efficacy of MRI and PET/CT in lung cancer of mouse with spinal metastasis

Toxicology and pharmacology of synthetic organoselenium compounds: an update

Development and Therapeutic Potential of Selenazo Compounds

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