Comparison of DSB effects of the beta particles of iodine-131 and 6 MV X-ray at a dose of 2 Gy in the presence of 2-Methoxyestradiol, IUdR, and TPT in glioblastoma spheroids

Neshasteh-Riz, Ali; Eyvazzadeh, Nazila; Koosha, Fereshteh; Cheraghi, Susan

doi:10.1016/j.radphyschem.2016.10.011

Cited by 7 publications

(6 citation statements)

References 21 publications

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“…However, despite the enormous improvements in treatment modalities, the management of GBM carries a dismal endeavor. Therefore, novel therapeutic approaches were restructured by motivation (Neshasteh-Riz et al, 2017;Osuka and Van Meir, 2017).…”

Section: Introductionmentioning

confidence: 99%

Cabazitaxel inhibits proliferation and potentiates the radiation response of U87MG glioblastoma cells

Neshasteh-Riz

Zeinizade

Safa

et al. 2018

Cell Biology International

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Cabazitaxel is a second-generation semisynthetic taxane. The recognized anti-neoplastic effect of Cabazitaxel is cell cycle perturbation by inducing arrest at G2/M. Since glioblastoma tumors have a relatively high expression of P-gp, it is encouraging to find a treatment that is effective against these tumors. This study was conducted to examine the radiosensitizing potential of Cabazitaxel against U87MG cells. In order to evaluate the effect of Cabazitaxel, cells were treated with different concentrations of the drug at different time intervals and then cytotoxicity and cell cycle were assessed using MTT and flow cytometry assays, respectively. Annexin/PI and real-time polymerase chain reaction (PCR) assays were used to evaluate the extent of apoptosis. Cabazitaxel exerted a consistent G2/M arrest and resulted in a concentration- and time-dependent toxicity. Cabazitaxel enhanced the cytotoxicity response of U87MG cells to radiation. Apoptosis increased following Cabazitaxel-IR administration. At the same time, these results were further supported by apoptotic genes regulation. This study provides the first preclinical evidence supporting that Cabazitaxel can render U87MG cells more susceptible to the cytotoxicity of radiation and could potentially be administered in combination modalities as a promising cell cycle-specific radiosensitizer for the future steps of in vivo evaluation.

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Section: Introductionmentioning

confidence: 99%

Cabazitaxel inhibits proliferation and potentiates the radiation response of U87MG glioblastoma cells

Neshasteh-Riz

Zeinizade

Safa

et al. 2018

Cell Biology International

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“…These platforms have numerous limitations and scientists have been looking for alternative platforms to mimic the real physiological properties of tissue and organs. Three-dimensional platforms, such as the spheroid system, can translate physiological functions of the tissue and organs of our body and the data acquired by 3D spheroids' cell-based platforms, and are more realistic than 2D cell culture systems [47][48][49]. In case of lung cancer, targeted therapy of lung cancer is highly dependent on the identification of the molecular mechanisms of progression and development, as well as prognosis, to open new avenues in this case [50].…”

Section: Resultsmentioning

confidence: 99%

Fingerprinting Metabolic Activity and Tissue Integrity of 3D Lung Cancer Spheroids under Gold Nanowire Treatment

Hashemzadeh

Kelkawi

Allahverdi

et al. 2022

Cells

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Inadequacy of most animal models for drug efficacy assessments has led to the development of improved in vitro models capable of mimicking in vivo exposure scenarios. Among others, 3D multicellular spheroid technology is considered to be one of the promising alternatives in the pharmaceutical drug discovery process. In addition to its physiological relevance, this method fulfills high-throughput and low-cost requirements for preclinical cell-based assays. Despite the increasing applications of spheroid technology in pharmaceutical screening, its application, in nanotoxicity testing is still in its infancy due to the limited penetration and uptake rates into 3D-cell assemblies. To gain a better understanding of gold nanowires (AuNWs) interactions with 3D spheroids, a comparative study of 2D monolayer cultures and 3D multicellular spheroids was conducted using two lung cancer cell lines (A549 and PC9). Cell apoptosis (live/dead assay), metabolic activity, and spheroid integrity were evaluated following exposure to AuNWs at different dose-time manners. Results revealed a distinct different cellular response between 2D and 3D cell cultures during AuNWs treatment including metabolic rates, cell viability, dose–response curves and, uptake rates. Our data also highlighted further need for more physiologically relevant tissue models to investigate in depth nanomaterial–biology interactions. It is important to note that higher concentrations of AuNWs with lower exposure times and lower concentrations of AuNWs with higher exposure times of 3 days resulted in the loss of spheroid integrity by disrupting cell–cell contacts. These findings could help to increase the understanding of AuNWs-induced toxicity on tissue levels and also contribute to the establishment of new analytical approaches for toxicological and drug screening studies.

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“…Interestingly, the reduction in survival fraction was more pronounced in cells On the other hand, in order to reach a high therapeutic index, targeted radionuclide therapy can be used to deliver high doses of radio-sensitizers to tumors. The effectiveness of TPT has been shown in the induction of DSB in different types of cancer, including breast, ovaries, lung, leukemia, non-Hodgkin lymphoma, melanoma, colorectal carcinoma, and glioblastoma [13]. Also, with regard to other investigations, 131I-Metaiodobenzylguanidine (131I-MIBG) has been demonstrated to have beneficial effects on the treatment of pheochromocytoma, paraganglioma [21,22], medullary thyroid cancer [23], and carcinoid tumors [24,25] with a high efficiency ranging from 30%-75%.…”

Section: Discussionmentioning

confidence: 99%

“…In a study conducted by Neshastehriz and colleagues, they revealed that iodine-131 is able to cause higher degrees of DSB in comparison with 6 MV X-ray when used at the same dose as a result of its crossfire effect and spatial distribution of energy in various angles. Besides, they indicated that the combinatory use of chemotherapy and iodine-131 exhibited higher efficacy compared with radiotherapy with a dose of 6 MV X-ray against glioblastoma cells [13]. By means of the crossfire effect, iodine-131 emits lethal doses of irradiation, preventing the proliferation of adjacent tumor cells [26].…”

Section: Bcl-2 Bax P53 and Gamma-h2ax Proteinsmentioning

confidence: 99%

“…Iodine-131, with a physical half-life of 8.04 days, can be used as a radiopharmaceutical agent, and its irradiation consists of beta (606 keV) and gamma (364 keV) particles. Beta-particles are capable of inducing cell damage and could be easily labeled with Tositumomab or MIBG [13]. Iodine-131, as a low-cost and easy labeling radionuclide, in addition to the creation of self-dose in surrounding cells, is able to transfer cross-dose to adjacent and distant cells, creating DNA strand breaks in cells and induce apoptosis.…”

Section: Introductionmentioning

confidence: 99%

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WITHDRAWN: The Effect of Iodine-131 Beta-particles in Combination With A-966492 and Topotecan on Radio-sensitization of Glioblastoma

Koosha

Eynali

Eyvazzadeh

2021

Preprint

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Glioblastoma tumors are resistant to radiotherapy, and the need for drugs to induce radio-sensitization in tumor cells has always been a challenge. Besides, radiotherapy using targeted radionuclide is effective even for resistant tumors. Poly (ADP-ribose) polymerase (PARP) and topoisomerase I enzymes have critical roles in the repairmen of DNA damage in cells. Thus, the inhibition of the activity of these enzymes can prevent the process of DNA repair and lead to the accumulation of damaged DNA in cells, resulting in the induction of cell death in tumors. In the current study, we investigated the effect of beta-particles of iodine-131 in combination with Topotecan (TPT), as the inhibitor of topoisomerase I, and A-966492, as the inhibitor of the PARP enzyme to increase radio-sensitivity of glioblastoma cells.The U87MG cell line (a human glioblastoma cell line) were cultured in Poly-Hema-coated flasks to reach 300μm-diameter spheroids. Then, the cells were treated with non-toxic concentrations of A-966492 and TPT. The viability of the cells treated with iodine131 in combination with A-966492 and TPT was determined by the clonogenic assay. The expression level of the gamma-H2AX protein, as a biomarker of DNA double-strand breaks, was measured by the immunofluorescence staining method to examine the impact of A-966492 (1μM), TPT, and radiation on the induction cell death.The combination of A-966492 and TPT with radiation resulted in the enhanced cell death, and sensitizer enhancement ratios at 50% survival (SER50) were 1.25 and 1.45, respectively. Radio- and chemo-sensitization were promoted when iodine-131 was combined with A-966492 and TPT, with the SER50 of 1.68. Also, the expression of γ-H2AX was significantly increased in cells treated with A-966492 and TPT combined with radiation.The results demonstrated that iodine-131, in combination with A-966492 and TPT, had marked effects on radio-sensitizing and can be used as a targeted radionuclide for targeting radiotherapy in combination with PARP and topoisomerase I inhibitors to improve radiotherapy in clinics.

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Comparison of DSB effects of the beta particles of iodine-131 and 6 MV X-ray at a dose of 2 Gy in the presence of 2-Methoxyestradiol, IUdR, and TPT in glioblastoma spheroids

Cited by 7 publications

References 21 publications

Cabazitaxel inhibits proliferation and potentiates the radiation response of U87MG glioblastoma cells

Cabazitaxel inhibits proliferation and potentiates the radiation response of U87MG glioblastoma cells

Fingerprinting Metabolic Activity and Tissue Integrity of 3D Lung Cancer Spheroids under Gold Nanowire Treatment

WITHDRAWN: The Effect of Iodine-131 Beta-particles in Combination With A-966492 and Topotecan on Radio-sensitization of Glioblastoma

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Comparison of DSB effects of the beta particles of iodine-131 and 6 MV X-ray at a dose of 2 Gy in the presence of 2-Methoxyestradiol, IUdR, and TPT in glioblastoma spheroids

Cited by 7 publications

References 21 publications

Cabazitaxel inhibits proliferation and potentiates the radiation response of U87MG glioblastoma cells

Cabazitaxel inhibits proliferation and potentiates the radiation response of U87MG glioblastoma cells

Fingerprinting Metabolic Activity and Tissue Integrity of 3D Lung Cancer Spheroids under Gold Nanowire Treatment

WITHDRAWN: The Effect of Iodine-131 Beta-particles in Combination With A-966492 and Topotecan&nbsp;on Radio-sensitization of Glioblastoma

Contact Info

Product

Resources

About

WITHDRAWN: The Effect of Iodine-131 Beta-particles in Combination With A-966492 and Topotecan on Radio-sensitization of Glioblastoma