جستجوی مقالات مرتبط با کلیدواژه "radioresistance" در نشریات گروه "پزشکی"

Gliomas are the most common lethal tumors of the brain associated with a poor prognosis and increased resistance to chemo-radiotherapy. Circular RNAs (circRNAs), newly identified noncoding RNAs, have appeared as critical regulators of therapeutic resistance among multiple cancers and gliomas. Since circRNAs are aberrantly expressed in glioma and may act as promoters or inhibitors of therapeutic resistance, we categorized alterations of these specific RNAs expression in therapy resistant-glioma in three different classes, including chemoresistance, radioresistance, and glioma stem cell (GSC)-regulation. circRNAs act as competing endogenous RNA, sponging target microRNA and consequently affecting the expression of genes related to glioma tumorigenesis and resistance. By doing so, circRNAs can modulate the critical cellular pathways and processes regulating glioma resistance, including DNA repair pathways, GSC, epithelial-mesenchymal transition, apoptosis, and autophagy. Considering the poor survival and increased resistance to currently approved treatments for glioma, it is crucial to increase the knowledge of the resistance regulatory effects of circRNAs and their underlying molecular mechanisms. Herein, we conducted a comprehensive search and discussed the existing knowledge regarding the important role eof circRNAs in the emergence of resistance to therapeutic interventions in glioma. This knowledge may serve as a basis for enhancing the effectiveness of glioma therapeutic strategies.

To determine whether and how cinobufagin regulates hepatocellular carcinoma (HCC) cell proliferation and radioresistance.

Radiosensitive (HepG2-NC) and radioresistant (HepG2-SR) HCC cells were treated with cinobufagin, X-ray ionizing radiation (IR) or a combination of cinobufagin and IR at different doses. Cell counting was performed using the Cell Counting Kit-8 assay. Key ferroptosis marker levels were determined using the indicated methods. RNA immunoprecipitation using an anti-m6A antibody followed by quantitative polymerase chain reaction was performed to determine the m6A levels in SLC7A11 mRNA.

Cinobufagin inhibited the proliferation of HepG2-NC and HepG2-SR cells. Exposure to X-rays decreased the HepG2-NC cell count in a time- and dose-dependent manner, but did not affect HepG2-SR cells. A low dose of cinobufagin did not change the cell count without IR exposure, but re-sensitized HepG2-SR cells to IR. The combination of low-dose cinobufagin and IR increased ferroptosis and decreased SLC7A11 expression levels. Mechanistically, the combination of a low dose of cinobufagin and IR decreased m6A levels in the 3' UTR of SLC7A11 in a METTL3-dependent manner.

A low dose of cinobufagin exerted synergistic effects with IR and re-sensitized radioresistant HCC cells to IR via a METTL3/m6A-dependent pathway.

Radiotherapy (RT) has been commonly applied to treat advanced local cancers. In radiation therapy, high doses of radiation are utilized to trigger cell death. Radiation often leads to DNA double-strand breakages (DSB), which causes the activation of downstream genes including those for non-coding RNAs (ncRNA) such as long non-coding and RNAsmicro RNAs. The consequence of RT significantly relies on the radiosensitivity of cancer cells, which is affected by multiple factors, including some proteins and cellular processes. Activation of these genes can cause cell cytotoxicity and indirectly damages the cells. Recent studies have shown that non-coding RNAs can play as radiosensitivity or radioinhibitory regulators in cancers by mechanisms such as cell cycle arrest or affecting the DNA damage repair systems. ncRNAs are also known to function as tumor suppressor genes or oncogenes in colorectal cancer and therefore are considered potential diagnostic biomarkers in disease detection. For example, the investigations have shown that miR-29a and miR-224 can be informative biomarkers for early detection or screening of CRC via a noninvasive method such as liquid biopsy. Here, we discuss ncRNAs involved in the radioresistance and radiosensitivity of CRC and highlight their predictive clinical value in response to RT. Accordingly, this review represents a principal guide in the context of three major types of ncRNAs with potential roles in the pathway of radiosensitivity and radioresistance, including miRNAs, lncRNAs, and circRNAs which can be considered a precious archivement in organizing additional studies and broadening views in this area. Our findings can also assist radiotherapists in predicting CRC patients’ response and, therefore, prognosis to radiation therapy, although, to achieve our goals in the clinic, we certainly need further studies.

Radiotherapy is a standard and effective modality for breast cancer treatment, through induction of DNA damages notably DNA double-strand breaks which are involved in radiation-induced cell death. All radiation-induced DNA damages are subjected to various repair processes, therefore, interference in the DNA repair pathways might result in radio-resistance. Non-coding RNAs are a diverse group of functional RNA molecules that are not translated into proteins. Recent studies have shown that radiation can cause expression changes in noncoding RNAs. MCF-7 and MDA-MB-231 cell lines were grown in a DMEM culture medium supplemented with fetal bovine serum and antibiotics. At exponential growth, cells were exposed to various doses of megavoltage X-rays. 24 and 48 h after irradiation cells were harvested, RNA was extracted and cDNA was synthesized. The expression level of lncRNAs was measured using quantitative real-time PCR. This study showed that radiation could increase DANCR and TUG1 lncRNAs expression in breast cancer cell lines 24 and 48 h after receiving radiation. Also, the results suggested that after radiation, the expression of DANCR in the radioresistant cell line was higher than the radiosensitive one; in the case of TUG1, it’s unlike DANCR. The radiation increased the expression of DANCR and TUG1 lncRNAs in breast cancer cell lines because the expression of DANCR in the MDA-MB- 231 was higher than in the MCF-7. In contrast, the expression level of TUG1 in MCF-7 was higher than the MDA-MB-231. Therefore, lncRNAs, DNACR, and TUG1 might play a role in the radioresistance and radiosensitivity of breast cancer, respectively.

Radiotherapy as the first-line nasopharyngeal carcinoma (NPC) treatment provides different responses including radioresistant and radiosensitive states. In order to investigate the molecular basis of radioresistancy, protein-protein interaction network analysis of proteome data prior to therapy was performed.

20 dysregulated proteins of the patients who were radioresistant were extracted from the literature . Cytoscape and its plug-ins were used for the resistant network construction and its centrality analysis. Furthermore, ClueGO+ CluePedia application determined the most statistically significant biological processes (BP) related to the hubs.

Fourteen hubs were concluded and no differentially expressed protein (DEP) was among these agents. Among the hubs, albumin (ALB) and fibronectin (FN1) were the hub-bottlenecks, and the Serpin family was present. What is more, SERPIND1 was the highest degree-valued DEP in the network.

It can be concluded that the central elements of the NPC network could be noteworthy for improving the radiotherapy outcome and overcoming its limitations. However, complementary studies are required for a better understanding of their major role.

While radiotherapy is the important modality in the treatment of breast cancer cells, radioresistance of some tumor cell lines such as MDA-MB-231 is still a limitation that must be considered.

The present study was done to examine the effect of the conditioned medium of the human umbilical cord Wharton's jelly stem cells (hWJSCs + CM) on the radiosensitivity of MDA-MB-231 cells in combination with megavoltage-radiations.

Groups are Control, CM, GY, and GY + CM. In irradiation groups, breast cancer cells were exposured with 4, 6, and 8 Gy radiation. Each group includes different doses of the conditioned medium of hWJSCs (25%, 50%, and 75%).

The MTT assay showed that the proliferative activity of Gy + CM groups at all doses of condition medium decreased significantly compared with the control, rather than Gy groups. Trypan blue viability test showed that the survival rate of MDA-MB-231 cells significantly reduced in the CM and 8 Gy + CM groups compared with the control group, rather than Gy groups. MDA-MB-231 cells lost their normal spindle shape and became thinner and longer after 48h of treatment and the number of cells sharply reduced in Gy + CM groups compared with the control group, rather than Gy groups. These changes were accompanied by inducing significant up-regulation of Interleukin-6 (IL-6) in the 4 Gy + CM and 8 Gy + CM groups compared with the control group, rather than Gy groups and as a consequence, a decrease in the amount of transmembrane tumor necrosis factor-α (tmTNF-α) as a pro-inflammatory cytokine in the Gy + CM groups compared with the control group, rather than Gy groups. Also, we indicated that the radiosensitivity of breast cancer cells was probably enhanced by an increase in different doses of the conditioned medium of stem cells.

Treatment of the MDA-MB-231 cells with hWJSCs + CM plus radiotherapy inhibited the growth and proliferation of cancer cells and this method is a novel strategy for breast cancer therapy by overcoming radioresistance.

Tumor radioresistance leads to a reduction in the efficiency of radiation therapy. It is very important to explore the cellular mechanisms leading to radioresistance and to find potential therapeutic targets, which might improve the efficacy of radiation therapy. This study was to investigate the role of ataxia-telangiectasia mutated (ATM) and murine double minute X (MDMX) in radioresistance in non-small cell lung cancer A549 cells and their corresponding mechanisms of action.

Non-small cell lung cancer A549 cells were irradiated with X-rays in the presence or absence of ATM inhibitor. Cell survival, cell apoptosis, cell proliferation, mRNA of ATM and MDMX, and protein expression of ATM, MDMX, γ-H2AX, Caspase3, and Beclin1 were measured.

After the inhibitor (KU60019) treatment combined with X irradiation, the A549 cells showed a significant decrease in colony formations compared to the group received irradiation alone. The MDMX knockdown A549 cells showed a significant increase in colony formations compared to the control group. ATM downregulated the expression of MDMX after irradiation treatment in A549 cells. Irradiation led to a significant increase in γ-H2AX expression, but MDMX knockdown decreased the γ-H2AX expression after irradiation. The change of Caspase3 expression was the same as γ-H2AX. Irradiation led to a significant increase of Beclin1 expression and MDMX knockdown increased the Beclin1 expression after irradiation.

This study indicated that ATM induced radioresistance through downregulating the expression of MDMX, which was at least partly associated with the activation of autophagy and the decrease of DNA damage in A549 cells.

Combination cancer therapy is a promising strategy which employs multiple therapeutic agents with different mechanisms of action along with minimal intolerable side effects. For example, a combination of radiotherapy with gene therapy can overcome the development of resistance to therapeutic doses of irradiation (IR) and normal tissue damages caused by high-dose radiation. Recent studies have revealed radio-resistance in non-small cell lung cancer (NSCLC) cells. In this study, for the first time, subunit B of cytolethal distending toxin (cdtB)-expressing plasmid was introduced as a sensitizer of the cells to IR with a high efficacy.
A vector expressing cdtB suicide gene of human periodontal bacterium Aggregatibacter actinomycetemcomitans was constructed and then transfected into A549 cell line. In the next step, cells transfected with pcDNA3.1/cdtB were irradiated and its growth inhibitory effect was evaluated in NSCLC cancer in vitro by MTT (3-(4, 5-methylthiazol-2-yl) -2, 5-diphenyl-tetrazolium bromide) assay. Terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were carried out in order to examine the apoptosis induction by a combination of IR with cdtB.
Our data indicated significant cell death in NSCLC cells in comparison with controls with an increase from 5% in response to IR up to 73.27% for combination of IR with cdtB. Moreover, the result of TUNEL assay showed significant differences in the number of apoptotic cells among the different affected groups.
Our results confirmed that cdtB-expressing plasmid sensitizes NSCLC cells to IR and significantly increases the efficacy of radiotherapy and therefore, combining toxin with IR has a synergistic effect on NSCLC.

Radiotherapy is an established therapeutic modality for prostate cancer. Resveratrol, a natural antioxidant, has been shown to inhibit carcinogenesis and to block the process of tumor initiation and progression. No data is available on the response of cellular spheroid to Reseveratol. In this study we have examined the effect of Resveratol on the radiation response of human prostate cell line DU145 in monolayer and spheroid cultures. Radiosensitivity was assessed using viability and colony formation assay. Apoptosis and necrosis were assessed using acridine orange/ ethidium bromide double staining. The colony formation assay did not show any significant radio-sensitizing effect, but apoptosis assay showed significant radio-sensitizing effect of Resveratol on DU145 cells grown as monolayer. In the spheroid cells the results of apoptosis test were not significant and corresponded closely to the result of survival curve. While Resveratol could sensitize DU145 cells in monolayer to ionizing radiation, it did not have any effect on sensitivity of cells cultured in spheroid cultures.

Radiotherapy is an established therapeutic modality for prostate cancer. Resveratrol, a natural antioxidant, has been shown to inhibit carcinogenesis and to block the process of tumor initiation and progression. No data is available on the response of cellular spheroid to Reseveratol. In this study we have examined the effect of Resveratol on the radiation response of human prostate cell line DU145 in monolayer and spheroid cultures. Radiosensitivity was assessed using viability and colony formation assay. Apoptosis and necrosis were assessed using acridine orange/ ethidium bromide double staining. The colony formation assay did not show any significant radio-sensitizing effect, but apoptosis assay showed significant radio-sensitizing effect of Resveratol on DU145 cells grown as monolayer. In the spheroid cells the results of apoptosis test were not significant and corresponded closely to the result of survival curve. While Resveratol could sensitize DU145 cells in monolayer to ionizing radiation, it did not have any effect on sensitivity of cells cultured in spheroid cultures.