The Experts below are selected from a list of 1014 Experts worldwide ranked by ideXlab platform
Jin Cheng - One of the best experts on this subject based on the ideXlab platform.
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caspase 3 knockout attenuates radiation induced Tumor Repopulation via impairing the atm p53 cox 2 pge 2 pathway in non small cell lung cancer
Aging, 2020Co-Authors: Minghui Zhao, Jin Cheng, Yanping Gong, Yiwei Wang, Yucui Zhao, Jian-zhu Xie, Yu-lan Wang, Yanwei Song, Ruyi Zhao, Ling TianAbstract:Radiotherapy is an effective treatment for non-small cell lung cancer (NSCLC). However, irradiated, dying Tumor cells generate potent growth stimulatory signals during radiotherapy that promote the Repopulation of adjacent surviving Tumor cells to cause Tumor recurrence. We investigated the function of caspase-3 in NSCLC Repopulation after radiotherapy. We found that radiotherapy induced a DNA damage response (DDR), activated caspase-3, and promoted Tumor Repopulation in NSCLC cells. Unexpectedly, caspase-3 knockout attenuated the ataxia-telangiectasia mutated (ATM)/p53-initiated DDR by decreasing nuclear migration of endonuclease G (EndoG), thereby reducing the growth-promoting effect of irradiated, dying Tumor cells. We also identified p53 as a regulator of the Cox-2/PGE2 axis and its involvement in caspase-3-induced Tumor Repopulation after radiotherapy. In addition, injection of caspase-3 knockout NSCLC cells impaired Tumor growth in a nude mouse model. Our findings reveal that caspase-3 promotes Tumor Repopulation in NSCLC cells by activating DDR and the downstream Cox-2/PGE2 axis. Thus, caspase-3-induced ATM/p53/Cox-2/PGE2 signaling pathway could provide potential therapeutic targets to reduce NSCLC recurrence after radiotherapy.
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Caspase-3 knockout attenuates radiation-induced Tumor Repopulation via impairing the ATM/p53/Cox-2/PGE2 pathway in non-small cell lung cancer.
Aging, 2020Co-Authors: Minghui Zhao, Jin Cheng, Yanping Gong, Yiwei Wang, Yucui Zhao, Jian-zhu Xie, Yanwei Song, Ruyi Zhao, Yu-lan WangAbstract:Radiotherapy is an effective treatment for non-small cell lung cancer (NSCLC). However, irradiated, dying Tumor cells generate potent growth stimulatory signals during radiotherapy that promote the Repopulation of adjacent surviving Tumor cells to cause Tumor recurrence. We investigated the function of caspase-3 in NSCLC Repopulation after radiotherapy. We found that radiotherapy induced a DNA damage response (DDR), activated caspase-3, and promoted Tumor Repopulation in NSCLC cells. Unexpectedly, caspase-3 knockout attenuated the ataxia-telangiectasia mutated (ATM)/p53-initiated DDR by decreasing nuclear migration of endonuclease G (EndoG), thereby reducing the growth-promoting effect of irradiated, dying Tumor cells. We also identified p53 as a regulator of the Cox-2/PGE2 axis and its involvement in caspase-3-induced Tumor Repopulation after radiotherapy. In addition, injection of caspase-3 knockout NSCLC cells impaired Tumor growth in a nude mouse model. Our findings reveal that caspase-3 promotes Tumor Repopulation in NSCLC cells by activating DDR and the downstream Cox-2/PGE2 axis. Thus, caspase-3-induced ATM/p53/Cox-2/PGE2 signaling pathway could provide potential therapeutic targets to reduce NSCLC recurrence after radiotherapy.
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Irradiation-Induced Polyploidy Giant Cancer Cells Mediate Tumor Cell Repopulation via Neosis
2020Co-Authors: Zhengxiang Zhang, Jin Cheng, Yiwei Wang, Minghui Zhao, Yucui Zhao, Feng Xiao, Qian HuangAbstract:Abstract Background Tumor Repopulation generally describes the phenomenon that residual Tumor cells surviving therapies tenaciously proliferate and reestablish the Tumor, presenting an embarrassing plight for cancer treatment. However, the cellular and molecular mechanisms underlying this process remains poorly understood. In this study, we proposed polyploidy giant cancer cells (PGCCs)-mediated and neosis-based Tumor Repopulation after radiotherapy.Methods The formation of PGCCs after irradiation was examined in vitro and in vivo. The demise of X-ray irradiated cells was detected by flow cytometry, clonogenic cell survival assay and transmission electron microscopy. Western blot was used to test cell proliferation and death related protein expression level of these irradiated cells. Time lapse microscopy was adopted to observe the destiny of PGCCs. The property of these PGCCs was identified by TUNEL assay, Brdu chasing assay, western blot, immunocytochemical and immunofluorescence staining. The relationship of HMGB1 with PGCCs-derived Tumor Repopulation was conducted via HMGB1 chemical inhibitors. Finally, animal model was used to verify the formation of PGCCs, and the relevance of HMGB1 in this process was investigated by immunohistochemical staining.Results The majority of PGCCs induced by irradiation move towards cell demise, whereas some of them intriguingly possessed proliferative property. Utilizing time-lapse microscopy and single-cell cloning assay, we observed that neosis derived from those PGCCs with proliferative capacity contributed to Tumor cell Repopulation after irradiation. Using the conditioned media collected from dying Tumor cells to perform single-cell cloning assay, we unexpectedly demonstrated that HMGB1 released from dying Tumor cells participated the process of neosis-based Tumor Repopulation. In irradiation treated animal Tumor bearing model, the expression level of HMGB1 increased after irradiation compare with non-irradiated group. Moreover, some PGCCs presented high HMGB1 expression. Interestingly, we also observed that the proliferation potential of PGCCs varied. Some PGCCs proliferated at early stage, while some PGCCs proliferated at late stage.Conclusion X-ray irradiation could induce the formation of PGCCs, which could move towards both cell death and survival; irradiation-generating PGCCs mediated Tumor cell Repopulation after irradiation via neosis; HMGB1 released from dying cells stimulated the process of neosis and participated in Tumor Repopulation after irradiation.
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Caspase-3 Silencing Attenuates Tumor Repopulation Via Impairing Radiation-Induced DNA Damage Response and Downstream Pathway in Non-Small-Cell Lung Cancer
2020Co-Authors: Minghui Zhao, Jin Cheng, Yanping Gong, Yiwei Wang, Yucui Zhao, Jian-zhu Xie, Yanwei Song, Ruyi Zhao, Yu-lan WangAbstract:Abstract Background: Radiotherapy is an effective treatment on non-small-cell lung cancer (NSCLC). However, radiation-induced dying Tumor cells are postulated to generate potent growth signals to stimulate the Repopulation of adjacent surviving Tumor cells, which may promote Tumor recurrence. We investigated the role of caspase-3-centered molecular mechanism in NSCLC Repopulation after radiotherapy.Methods: The stable caspase-3 knockout (Casp3 KO) NSCLC cells were compared with wild-type cells for growth-promoting effect after radiotherapy using in vitro Repopulation model. Western blotting, quantitative real-time PCR, enzyme-linked immunosorbent assay and luciferase reporter assay were used to identify the possible molecules and pathway. To elucidate the function of caspase-3 in Tumor Repopulation, a series of in vitro assays were performed with Casp3 KO NSCLC cells. Finally, Tumor cell growth rate of Casp3 KO and wild-type Tumor cells in vivo was tested using xenograft Tumor assay and key proteins were further confirmed in Tumor tissues with or without radiotherapy.Results: We found that radiation induced DNA damage response (DDR) and caspase-3 activation, as well as promoted Tumor Repopulation in NSCLC cells. Unexpectedly, depleting caspase-3 significantly attenuated ataxia-telangiectasia mutated kinase (ATM)/p53-mediated DDR via attenuating endonuclease G (EndoG) nuclear migration, thus decreasing the growth-promoting effect of irradiated dying cells. Moreover, we identified p53 as a regulator of the Cox-2/PGE2 axis, which was probably involved in caspase-3-centered Tumor Repopulation after radiotherapy. Additionally, depleting caspase-3 in NSCLC cells showed impaired Tumor growth in nude mice model.Conclusions: Our findings demonstrated that caspase-3 was implicated in Tumor Repopulation and that was accompanied by promoting DDR and downstream Cox-2/PGE2 axis activation in NSCLC cells. This hitherto undescribed signaling pathway mediated by caspase-3 may deepen insight into the radiobiology and provide therapeutic targets to reduce NSCLC recurrence after radiotherapy.
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Necroptosis regulates Tumor Repopulation after radiotherapy via RIP1/RIP3/MLKL/JNK/IL8 pathway.
Journal of experimental & clinical cancer research : CR, 2019Co-Authors: Yiwei Wang, Jin Cheng, Yanping Gong, Minghui Zhao, Yuntao Luo, Yucui Zhao, Jian-zhu Xie, Yu-lan WangAbstract:Tumor cell Repopulation after radiotherapy is a major cause for the Tumor radioresistance and recurrence. This study aims to investigate the underlying mechanism of Tumor Repopulation after radiotherapy, with focus on whether and how necroptosis takes part in this process. Necroptosis after irradiation were examined in vitro and in vivo. And the growth-promoting effect of necroptotic cells was investigated by chemical inhibitors or shRNA against necroptosis associated proteins and genes in in vitro and in vivo Tumor Repopulation models. Downstream relevance factors of necroptosis were identified by western blot and chemiluminescent immunoassays. Finally, the immunohistochemistry staining of identified necroptosis association growth stimulation factor was conducted in human colorectal Tumor specimens to verify the relationship with clinical outcome. Radiation-induced necroptosis depended on activation of RIP1/RIP3/MLKL pathway, and the evidence in vitro and in vivo demonstrated that the inhibition of necroptosis attenuated growth-stimulating effects of irradiated Tumor cells on living Tumor reporter cells. The JNK/IL-8 were identified as downstream molecules of pMLKL during necroptosis, and inhibition of JNK, IL-8 or IL-8 receptor significantly reduced Tumor Repopulation after radiotherapy. Moreover, the high expression of IL-8 was associated with poor clinical prognosis in colorectal cancer patients. Necroptosis associated Tumor Repopulation after radiotherapy depended on activation of RIP1/RIP3/MLKL/JNK/IL-8 pathway. This novel pathway provided new insight into understanding the mechanism of Tumor radioresistance and Repopulation, and MLKL/JNK/IL-8 could be developed as promising targets for blocking Tumor Repopulation to enhance the efficacy of colorectal cancer radiotherapy.
Yiwei Wang - One of the best experts on this subject based on the ideXlab platform.
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Caspase-3 knockout attenuates radiation-induced Tumor Repopulation via impairing the ATM/p53/Cox-2/PGE2 pathway in non-small cell lung cancer.
Aging, 2020Co-Authors: Minghui Zhao, Jin Cheng, Yanping Gong, Yiwei Wang, Yucui Zhao, Jian-zhu Xie, Yanwei Song, Ruyi Zhao, Yu-lan WangAbstract:Radiotherapy is an effective treatment for non-small cell lung cancer (NSCLC). However, irradiated, dying Tumor cells generate potent growth stimulatory signals during radiotherapy that promote the Repopulation of adjacent surviving Tumor cells to cause Tumor recurrence. We investigated the function of caspase-3 in NSCLC Repopulation after radiotherapy. We found that radiotherapy induced a DNA damage response (DDR), activated caspase-3, and promoted Tumor Repopulation in NSCLC cells. Unexpectedly, caspase-3 knockout attenuated the ataxia-telangiectasia mutated (ATM)/p53-initiated DDR by decreasing nuclear migration of endonuclease G (EndoG), thereby reducing the growth-promoting effect of irradiated, dying Tumor cells. We also identified p53 as a regulator of the Cox-2/PGE2 axis and its involvement in caspase-3-induced Tumor Repopulation after radiotherapy. In addition, injection of caspase-3 knockout NSCLC cells impaired Tumor growth in a nude mouse model. Our findings reveal that caspase-3 promotes Tumor Repopulation in NSCLC cells by activating DDR and the downstream Cox-2/PGE2 axis. Thus, caspase-3-induced ATM/p53/Cox-2/PGE2 signaling pathway could provide potential therapeutic targets to reduce NSCLC recurrence after radiotherapy.
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caspase 3 knockout attenuates radiation induced Tumor Repopulation via impairing the atm p53 cox 2 pge 2 pathway in non small cell lung cancer
Aging, 2020Co-Authors: Minghui Zhao, Jin Cheng, Yanping Gong, Yiwei Wang, Yucui Zhao, Jian-zhu Xie, Yu-lan Wang, Yanwei Song, Ruyi Zhao, Ling TianAbstract:Radiotherapy is an effective treatment for non-small cell lung cancer (NSCLC). However, irradiated, dying Tumor cells generate potent growth stimulatory signals during radiotherapy that promote the Repopulation of adjacent surviving Tumor cells to cause Tumor recurrence. We investigated the function of caspase-3 in NSCLC Repopulation after radiotherapy. We found that radiotherapy induced a DNA damage response (DDR), activated caspase-3, and promoted Tumor Repopulation in NSCLC cells. Unexpectedly, caspase-3 knockout attenuated the ataxia-telangiectasia mutated (ATM)/p53-initiated DDR by decreasing nuclear migration of endonuclease G (EndoG), thereby reducing the growth-promoting effect of irradiated, dying Tumor cells. We also identified p53 as a regulator of the Cox-2/PGE2 axis and its involvement in caspase-3-induced Tumor Repopulation after radiotherapy. In addition, injection of caspase-3 knockout NSCLC cells impaired Tumor growth in a nude mouse model. Our findings reveal that caspase-3 promotes Tumor Repopulation in NSCLC cells by activating DDR and the downstream Cox-2/PGE2 axis. Thus, caspase-3-induced ATM/p53/Cox-2/PGE2 signaling pathway could provide potential therapeutic targets to reduce NSCLC recurrence after radiotherapy.
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Irradiation-Induced Polyploidy Giant Cancer Cells Mediate Tumor Cell Repopulation via Neosis
2020Co-Authors: Zhengxiang Zhang, Jin Cheng, Yiwei Wang, Minghui Zhao, Yucui Zhao, Feng Xiao, Qian HuangAbstract:Abstract Background Tumor Repopulation generally describes the phenomenon that residual Tumor cells surviving therapies tenaciously proliferate and reestablish the Tumor, presenting an embarrassing plight for cancer treatment. However, the cellular and molecular mechanisms underlying this process remains poorly understood. In this study, we proposed polyploidy giant cancer cells (PGCCs)-mediated and neosis-based Tumor Repopulation after radiotherapy.Methods The formation of PGCCs after irradiation was examined in vitro and in vivo. The demise of X-ray irradiated cells was detected by flow cytometry, clonogenic cell survival assay and transmission electron microscopy. Western blot was used to test cell proliferation and death related protein expression level of these irradiated cells. Time lapse microscopy was adopted to observe the destiny of PGCCs. The property of these PGCCs was identified by TUNEL assay, Brdu chasing assay, western blot, immunocytochemical and immunofluorescence staining. The relationship of HMGB1 with PGCCs-derived Tumor Repopulation was conducted via HMGB1 chemical inhibitors. Finally, animal model was used to verify the formation of PGCCs, and the relevance of HMGB1 in this process was investigated by immunohistochemical staining.Results The majority of PGCCs induced by irradiation move towards cell demise, whereas some of them intriguingly possessed proliferative property. Utilizing time-lapse microscopy and single-cell cloning assay, we observed that neosis derived from those PGCCs with proliferative capacity contributed to Tumor cell Repopulation after irradiation. Using the conditioned media collected from dying Tumor cells to perform single-cell cloning assay, we unexpectedly demonstrated that HMGB1 released from dying Tumor cells participated the process of neosis-based Tumor Repopulation. In irradiation treated animal Tumor bearing model, the expression level of HMGB1 increased after irradiation compare with non-irradiated group. Moreover, some PGCCs presented high HMGB1 expression. Interestingly, we also observed that the proliferation potential of PGCCs varied. Some PGCCs proliferated at early stage, while some PGCCs proliferated at late stage.Conclusion X-ray irradiation could induce the formation of PGCCs, which could move towards both cell death and survival; irradiation-generating PGCCs mediated Tumor cell Repopulation after irradiation via neosis; HMGB1 released from dying cells stimulated the process of neosis and participated in Tumor Repopulation after irradiation.
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Caspase-3 Silencing Attenuates Tumor Repopulation Via Impairing Radiation-Induced DNA Damage Response and Downstream Pathway in Non-Small-Cell Lung Cancer
2020Co-Authors: Minghui Zhao, Jin Cheng, Yanping Gong, Yiwei Wang, Yucui Zhao, Jian-zhu Xie, Yanwei Song, Ruyi Zhao, Yu-lan WangAbstract:Abstract Background: Radiotherapy is an effective treatment on non-small-cell lung cancer (NSCLC). However, radiation-induced dying Tumor cells are postulated to generate potent growth signals to stimulate the Repopulation of adjacent surviving Tumor cells, which may promote Tumor recurrence. We investigated the role of caspase-3-centered molecular mechanism in NSCLC Repopulation after radiotherapy.Methods: The stable caspase-3 knockout (Casp3 KO) NSCLC cells were compared with wild-type cells for growth-promoting effect after radiotherapy using in vitro Repopulation model. Western blotting, quantitative real-time PCR, enzyme-linked immunosorbent assay and luciferase reporter assay were used to identify the possible molecules and pathway. To elucidate the function of caspase-3 in Tumor Repopulation, a series of in vitro assays were performed with Casp3 KO NSCLC cells. Finally, Tumor cell growth rate of Casp3 KO and wild-type Tumor cells in vivo was tested using xenograft Tumor assay and key proteins were further confirmed in Tumor tissues with or without radiotherapy.Results: We found that radiation induced DNA damage response (DDR) and caspase-3 activation, as well as promoted Tumor Repopulation in NSCLC cells. Unexpectedly, depleting caspase-3 significantly attenuated ataxia-telangiectasia mutated kinase (ATM)/p53-mediated DDR via attenuating endonuclease G (EndoG) nuclear migration, thus decreasing the growth-promoting effect of irradiated dying cells. Moreover, we identified p53 as a regulator of the Cox-2/PGE2 axis, which was probably involved in caspase-3-centered Tumor Repopulation after radiotherapy. Additionally, depleting caspase-3 in NSCLC cells showed impaired Tumor growth in nude mice model.Conclusions: Our findings demonstrated that caspase-3 was implicated in Tumor Repopulation and that was accompanied by promoting DDR and downstream Cox-2/PGE2 axis activation in NSCLC cells. This hitherto undescribed signaling pathway mediated by caspase-3 may deepen insight into the radiobiology and provide therapeutic targets to reduce NSCLC recurrence after radiotherapy.
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Necroptosis regulates Tumor Repopulation after radiotherapy via RIP1/RIP3/MLKL/JNK/IL8 pathway.
Journal of experimental & clinical cancer research : CR, 2019Co-Authors: Yiwei Wang, Jin Cheng, Yanping Gong, Minghui Zhao, Yuntao Luo, Yucui Zhao, Jian-zhu Xie, Yu-lan WangAbstract:Tumor cell Repopulation after radiotherapy is a major cause for the Tumor radioresistance and recurrence. This study aims to investigate the underlying mechanism of Tumor Repopulation after radiotherapy, with focus on whether and how necroptosis takes part in this process. Necroptosis after irradiation were examined in vitro and in vivo. And the growth-promoting effect of necroptotic cells was investigated by chemical inhibitors or shRNA against necroptosis associated proteins and genes in in vitro and in vivo Tumor Repopulation models. Downstream relevance factors of necroptosis were identified by western blot and chemiluminescent immunoassays. Finally, the immunohistochemistry staining of identified necroptosis association growth stimulation factor was conducted in human colorectal Tumor specimens to verify the relationship with clinical outcome. Radiation-induced necroptosis depended on activation of RIP1/RIP3/MLKL pathway, and the evidence in vitro and in vivo demonstrated that the inhibition of necroptosis attenuated growth-stimulating effects of irradiated Tumor cells on living Tumor reporter cells. The JNK/IL-8 were identified as downstream molecules of pMLKL during necroptosis, and inhibition of JNK, IL-8 or IL-8 receptor significantly reduced Tumor Repopulation after radiotherapy. Moreover, the high expression of IL-8 was associated with poor clinical prognosis in colorectal cancer patients. Necroptosis associated Tumor Repopulation after radiotherapy depended on activation of RIP1/RIP3/MLKL/JNK/IL-8 pathway. This novel pathway provided new insight into understanding the mechanism of Tumor radioresistance and Repopulation, and MLKL/JNK/IL-8 could be developed as promising targets for blocking Tumor Repopulation to enhance the efficacy of colorectal cancer radiotherapy.
Qian Huang - One of the best experts on this subject based on the ideXlab platform.
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Gene Panel of Persister Cells as a Prognostic Indicator for Tumor Repopulation After Radiation
Frontiers in Oncology, 2020Co-Authors: Yucui Zhao, Minghui Zhao, Yanwei Song, Ruyi Zhao, Qian HuangAbstract:Tumor Repopulation during cycles of radiotherapy limits the radio-response in ensuing cycles and causes failure of treatment. It is thus of vital importance to unveil the mechanisms underlying Tumor repopulating cells. Increasing evidence suggests that a subpopulation of drug-tolerant persister cancer cells (DTPs) could survive the cytotoxic treatment and resume to propagate. Whether these persister cells contribute to development of radio-resistance remains elusive. Based on the genetic profiling of DTPs by integrating datasets from Gene Expression Omnibus database, this study aimed to provide novel insights into Tumor-Repopulation mediated radio-resistance and identify predictive biomarkers for radio-response in clinic. A prognostic risk index, grounded on four persister genes (LYNX1, SYNPO, GADD45B, and PDLIM1), was constructed in non-small-cell lung cancer patients from The Cancer Genome Atlas Program (TCGA) using stepwise Cox regression analysis. Weighted gene co-expression network analysis further confirmed the interaction among persister-gene based risk score, radio-response and overall survival time. In addition, the predictive role of risk index was validated in vitro and in other types of TCGA patients. Gene set enrichment analysis was performed to decipher the possible biological signaling, which indicated that two forces behind persister cells, stress response and survival adaptation, might fuel the Tumor Repopulation after radiation. Targeting these persister cells may represent a new prognostic and therapeutic approach to enhance radio-response and prevent radio-resistance induced by Tumor Repopulation.
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Irradiation-Induced Polyploidy Giant Cancer Cells Mediate Tumor Cell Repopulation via Neosis
2020Co-Authors: Zhengxiang Zhang, Jin Cheng, Yiwei Wang, Minghui Zhao, Yucui Zhao, Feng Xiao, Qian HuangAbstract:Abstract Background Tumor Repopulation generally describes the phenomenon that residual Tumor cells surviving therapies tenaciously proliferate and reestablish the Tumor, presenting an embarrassing plight for cancer treatment. However, the cellular and molecular mechanisms underlying this process remains poorly understood. In this study, we proposed polyploidy giant cancer cells (PGCCs)-mediated and neosis-based Tumor Repopulation after radiotherapy.Methods The formation of PGCCs after irradiation was examined in vitro and in vivo. The demise of X-ray irradiated cells was detected by flow cytometry, clonogenic cell survival assay and transmission electron microscopy. Western blot was used to test cell proliferation and death related protein expression level of these irradiated cells. Time lapse microscopy was adopted to observe the destiny of PGCCs. The property of these PGCCs was identified by TUNEL assay, Brdu chasing assay, western blot, immunocytochemical and immunofluorescence staining. The relationship of HMGB1 with PGCCs-derived Tumor Repopulation was conducted via HMGB1 chemical inhibitors. Finally, animal model was used to verify the formation of PGCCs, and the relevance of HMGB1 in this process was investigated by immunohistochemical staining.Results The majority of PGCCs induced by irradiation move towards cell demise, whereas some of them intriguingly possessed proliferative property. Utilizing time-lapse microscopy and single-cell cloning assay, we observed that neosis derived from those PGCCs with proliferative capacity contributed to Tumor cell Repopulation after irradiation. Using the conditioned media collected from dying Tumor cells to perform single-cell cloning assay, we unexpectedly demonstrated that HMGB1 released from dying Tumor cells participated the process of neosis-based Tumor Repopulation. In irradiation treated animal Tumor bearing model, the expression level of HMGB1 increased after irradiation compare with non-irradiated group. Moreover, some PGCCs presented high HMGB1 expression. Interestingly, we also observed that the proliferation potential of PGCCs varied. Some PGCCs proliferated at early stage, while some PGCCs proliferated at late stage.Conclusion X-ray irradiation could induce the formation of PGCCs, which could move towards both cell death and survival; irradiation-generating PGCCs mediated Tumor cell Repopulation after irradiation via neosis; HMGB1 released from dying cells stimulated the process of neosis and participated in Tumor Repopulation after irradiation.
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Dying Tumor cell-derived exosomal miR-194-5p potentiates survival and Repopulation of Tumor repopulating cells upon radiotherapy in pancreatic cancer.
Molecular cancer, 2020Co-Authors: Ming-jie Jiang, Juan-juan Dai, Qian Huang, Yi-yun Chen, Zhu Mei, Furao Liu, Ling TianAbstract:Tumor Repopulation is a major cause of radiotherapy failure. Previous investigations highlighted that dying Tumor cells played vital roles in Tumor Repopulation through promoting proliferation of the residual Tumor repopulating cells (TRCs). However, TRCs also suffer DNA damage after radiotherapy, and might undergo mitotic catastrophe under the stimulation of proliferative factors released by dying cells. Hence, we intend to find out how these paradoxical biological processes coordinated to potentiate Tumor Repopulation after radiotherapy. Tumor Repopulation models in vitro and in vivo were used for evaluating the therapy response and dissecting underlying mechanisms. RNA-seq was performed to find out the signaling changes and identify the significantly changed miRNAs. qPCR, western blot, IHC, FACS, colony formation assay, etc. were carried out to analyze the molecules and cells. Exosomes derived from dying Tumor cells induced G1/S arrest and promoted DNA damage response to potentiate survival of TRCs through delivering miR-194-5p, which further modulated E2F3 expression. Moreover, exosomal miR-194-5p alleviated the harmful effects of oncogenic HMGA2 under radiotherapy. After a latent time, dying Tumor cells further released a large amount of PGE2 to boost proliferation of the recovered TRCs, and orchestrated the Repopulation cascades. Of note, low-dose aspirin was found to suppress pancreatic cancer Repopulation upon radiation via inhibiting secretion of exosomes and PGE2. Exosomal miR-194-5p enhanced DNA damage response in TRCs to potentiate Tumor Repopulation. Combined use of aspirin and radiotherapy might benefit pancreatic cancer patients.
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Dark Side of Cytotoxic Therapy: Chemoradiation-Induced Cell Death and Tumor Repopulation.
Trends in cancer, 2020Co-Authors: Ming-jie Jiang, Juan-juan Dai, Qian Huang, Ling TianAbstract:Accelerated Tumor Repopulation following chemoradiation is often observed in the clinic, but the underlying mechanisms remain unclear. In recent years, dying cells caused by chemoradiation have attracted much attention, and they may manifest diverse forms of cell death and release complex factors and thus orchestrate Tumor Repopulation cascades. Dying cells potentiate the survival of residual living Tumor cells, remodel the Tumor microenvironment, boost cell proliferation, and accelerate cancer cell metastasis. Moreover, dying cells also mediate the side effects of chemoradiation. These findings suggest more caution when weighing the benefits of cytotoxic therapy and the need to accordingly develop new strategies for cancer treatment.
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Aspirin in pancreatic cancer: chemopreventive effects and therapeutic potentials.
Biochimica et biophysica acta, 2016Co-Authors: Ming-jie Jiang, Juan-juan Dai, Qian Huang, Ling TianAbstract:Pancreatic cancer is one of the most aggressive malignancies with dismal prognosis. Recently, aspirin has been found to be an effective chemopreventive agent for many solid Tumors. However, the function of aspirin use in pancreatic cancer largely remains unknown. We herein argued that aspirin could also lower the risk of pancreatic cancer. Importantly, aspirin assumes pleiotropic effects by targeting multiple molecules. It could further target the unique Tumor biology of pancreatic cancer and modify the cancer microenvironment, thus showing remarkable therapeutic potentials. Besides, aspirin could reverse the chemoradiation resistance by repressing Tumor Repopulation and exert synergistic potentials with metformin on pancreatic cancer chemoprevention. Moreover, aspirin secondarily benefits pancreatic cancer patients through modestly reducing cancer pain and the risk of venous thromboembolism. Furthermore, new aspirin derivatives and delivery systems might help to improve risk-to-benefit ratio. In brief, aspirin is a promising chemopreventive agent and exerts significant therapeutic potentials in pancreatic cancer.
Ling Tian - One of the best experts on this subject based on the ideXlab platform.
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caspase 3 knockout attenuates radiation induced Tumor Repopulation via impairing the atm p53 cox 2 pge 2 pathway in non small cell lung cancer
Aging, 2020Co-Authors: Minghui Zhao, Jin Cheng, Yanping Gong, Yiwei Wang, Yucui Zhao, Jian-zhu Xie, Yu-lan Wang, Yanwei Song, Ruyi Zhao, Ling TianAbstract:Radiotherapy is an effective treatment for non-small cell lung cancer (NSCLC). However, irradiated, dying Tumor cells generate potent growth stimulatory signals during radiotherapy that promote the Repopulation of adjacent surviving Tumor cells to cause Tumor recurrence. We investigated the function of caspase-3 in NSCLC Repopulation after radiotherapy. We found that radiotherapy induced a DNA damage response (DDR), activated caspase-3, and promoted Tumor Repopulation in NSCLC cells. Unexpectedly, caspase-3 knockout attenuated the ataxia-telangiectasia mutated (ATM)/p53-initiated DDR by decreasing nuclear migration of endonuclease G (EndoG), thereby reducing the growth-promoting effect of irradiated, dying Tumor cells. We also identified p53 as a regulator of the Cox-2/PGE2 axis and its involvement in caspase-3-induced Tumor Repopulation after radiotherapy. In addition, injection of caspase-3 knockout NSCLC cells impaired Tumor growth in a nude mouse model. Our findings reveal that caspase-3 promotes Tumor Repopulation in NSCLC cells by activating DDR and the downstream Cox-2/PGE2 axis. Thus, caspase-3-induced ATM/p53/Cox-2/PGE2 signaling pathway could provide potential therapeutic targets to reduce NSCLC recurrence after radiotherapy.
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Analysis of exosomal circRNAs upon irradiation in pancreatic cancer cell Repopulation.
BMC medical genomics, 2020Co-Authors: Yi-yun Chen, Ming-jie Jiang, Ling TianAbstract:Pancreatic cancer is one of the most malignant Tumors. However, radiotherapy can lead to Tumor recurrence, which is caused by the residual surviving cells Repopulation stimulated by some molecular released from dying cells. Exosomes may mediate cell-cell communication and transfer kinds of signals from the dying cells to the surviving cells for stimulating Tumor Repopulation. Circular RNAs (circRNAs) may be one vital kind of exosomal cargos involving in modulating cancer cell Repopulation. Next generation sequencing (NGS) and bioinformatics were performed to analyze and annotate the expression and function of exosome-derived circRNAs in pancreatic cancer cells after radiation. Four circRNAs were chosen for qRT-PCR analysis to validate the sequencing results. In this study, 3580 circRNAs were annotated in literatures and circBase among 12,572 identified circRNAs. There were 196 filtered differentially expressed circRNAs (the up-regulation and down-regulation respectively is 182 and 14, fold change > 2, p-value
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Analysis of exosomal circRNAs upon irradiation in pancreatic cancer cell Repopulation
2020Co-Authors: Yi-yun Chen, Ming-jie Jiang, Zhi-long Chen, Ling TianAbstract:Abstract Background: Pancreatic cancer is one of the most malignant Tumors. However, radiotherapy can lead to Tumor recurrence, which is caused by the residual surviving cells Repopulation stimulated by some molecular released from dying cells. Exosomes may mediate cell-cell communication and transfer kinds of signals from the dying cells to the surviving cells for stimulating Tumor Repopulation. Circular RNAs (circRNAs) may be one vital kind of exosomal cargos involving in modulating cancer cell Repopulation. Methods: Next generation sequencing (NGS) and bioinformatics were performed to analyze and annotate the expression and function of exosome-derived circRNAs in pancreatic cancer cells after radiation. 4 circRNAs were chosen for qRT-PCR analysis to validate the sequencing results. Results: In this study, 3,580 circRNAs were annotated in literatures and circBase among 12,572 identified circRNAs. There were 196 filtered differentially expressed circRNAs (the up-regulation and down-regulation respectively is 182 and 14, fold change >2, p-value <0.05). Regulation of metabolic process and lysine degradation were the main enriched biological processes and pathway according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Conclusions: The hsa_circ_0002130-hsa_miR_4482-3p-NBN interaction network suggested potential sponging miRNA and target mRNA. Our results provided potential functions of circRNAs to explore molecular mechanisms and therapeutic targets in pancreatic cancer cell Repopulation upon irradiation.
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Analysis of exosomal circRNAs upon irradiation in pancreatic cancer cell Repopulation
2020Co-Authors: Yi-yun Chen, Ming-jie Jiang, Zhi-long Chen, Ling TianAbstract:Abstract Background : Pancreatic cancer is one of most malignant Tumors. However, radiotherapy can lead to Tumor recurrence, which is caused by the residual surviving cells Repopulation stimulated by some molecular released from dying cells. Exosomes may mediate cell-cell communication and transfer kinds of signals from the dying cells to the surviving cells for stimulating Tumor Repopulation. Circular RNAs (circRNAs) may be one vital kind of exosomal cargos involving in modulating cancer cell Repopulation. Methods: Next generation sequencing (NGS) and bioinformatics were performed to analyze and annotate the expression and function of exosome-derived circRNAs in pancreatic cells during radiation. 4 circRNAs were chosen for qRT-PCR analysis to validate the sequencing results. Results: In this study, 3,580 circRNAs were annotated in literatures and circBase among 12,572 identified circRNAs. There were 196 filtered differentially expressed circRNAs (the up-regulation and down-regulation respectively is 182 and 14, fold change >2, p-value <0.05). Regulation of metabolic process and lysine degradation were the main biological processes and pathway enrichment according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Conclusions: The hsa_circ_0002130-hsa_miR_4482-3p-NBN interaction network suggested potential miRNA sponge and target mRNA. Our results provided potential functions of circRNAs to explore molecular mechanisms and therapeutic targets in pancreatic cancer cell Repopulation upon irradiation.
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Dying Tumor cell-derived exosomal miR-194-5p potentiates survival and Repopulation of Tumor repopulating cells upon radiotherapy in pancreatic cancer.
Molecular cancer, 2020Co-Authors: Ming-jie Jiang, Juan-juan Dai, Qian Huang, Yi-yun Chen, Zhu Mei, Furao Liu, Ling TianAbstract:Tumor Repopulation is a major cause of radiotherapy failure. Previous investigations highlighted that dying Tumor cells played vital roles in Tumor Repopulation through promoting proliferation of the residual Tumor repopulating cells (TRCs). However, TRCs also suffer DNA damage after radiotherapy, and might undergo mitotic catastrophe under the stimulation of proliferative factors released by dying cells. Hence, we intend to find out how these paradoxical biological processes coordinated to potentiate Tumor Repopulation after radiotherapy. Tumor Repopulation models in vitro and in vivo were used for evaluating the therapy response and dissecting underlying mechanisms. RNA-seq was performed to find out the signaling changes and identify the significantly changed miRNAs. qPCR, western blot, IHC, FACS, colony formation assay, etc. were carried out to analyze the molecules and cells. Exosomes derived from dying Tumor cells induced G1/S arrest and promoted DNA damage response to potentiate survival of TRCs through delivering miR-194-5p, which further modulated E2F3 expression. Moreover, exosomal miR-194-5p alleviated the harmful effects of oncogenic HMGA2 under radiotherapy. After a latent time, dying Tumor cells further released a large amount of PGE2 to boost proliferation of the recovered TRCs, and orchestrated the Repopulation cascades. Of note, low-dose aspirin was found to suppress pancreatic cancer Repopulation upon radiation via inhibiting secretion of exosomes and PGE2. Exosomal miR-194-5p enhanced DNA damage response in TRCs to potentiate Tumor Repopulation. Combined use of aspirin and radiotherapy might benefit pancreatic cancer patients.
Yanping Gong - One of the best experts on this subject based on the ideXlab platform.
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Caspase-3 knockout attenuates radiation-induced Tumor Repopulation via impairing the ATM/p53/Cox-2/PGE2 pathway in non-small cell lung cancer.
Aging, 2020Co-Authors: Minghui Zhao, Jin Cheng, Yanping Gong, Yiwei Wang, Yucui Zhao, Jian-zhu Xie, Yanwei Song, Ruyi Zhao, Yu-lan WangAbstract:Radiotherapy is an effective treatment for non-small cell lung cancer (NSCLC). However, irradiated, dying Tumor cells generate potent growth stimulatory signals during radiotherapy that promote the Repopulation of adjacent surviving Tumor cells to cause Tumor recurrence. We investigated the function of caspase-3 in NSCLC Repopulation after radiotherapy. We found that radiotherapy induced a DNA damage response (DDR), activated caspase-3, and promoted Tumor Repopulation in NSCLC cells. Unexpectedly, caspase-3 knockout attenuated the ataxia-telangiectasia mutated (ATM)/p53-initiated DDR by decreasing nuclear migration of endonuclease G (EndoG), thereby reducing the growth-promoting effect of irradiated, dying Tumor cells. We also identified p53 as a regulator of the Cox-2/PGE2 axis and its involvement in caspase-3-induced Tumor Repopulation after radiotherapy. In addition, injection of caspase-3 knockout NSCLC cells impaired Tumor growth in a nude mouse model. Our findings reveal that caspase-3 promotes Tumor Repopulation in NSCLC cells by activating DDR and the downstream Cox-2/PGE2 axis. Thus, caspase-3-induced ATM/p53/Cox-2/PGE2 signaling pathway could provide potential therapeutic targets to reduce NSCLC recurrence after radiotherapy.
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caspase 3 knockout attenuates radiation induced Tumor Repopulation via impairing the atm p53 cox 2 pge 2 pathway in non small cell lung cancer
Aging, 2020Co-Authors: Minghui Zhao, Jin Cheng, Yanping Gong, Yiwei Wang, Yucui Zhao, Jian-zhu Xie, Yu-lan Wang, Yanwei Song, Ruyi Zhao, Ling TianAbstract:Radiotherapy is an effective treatment for non-small cell lung cancer (NSCLC). However, irradiated, dying Tumor cells generate potent growth stimulatory signals during radiotherapy that promote the Repopulation of adjacent surviving Tumor cells to cause Tumor recurrence. We investigated the function of caspase-3 in NSCLC Repopulation after radiotherapy. We found that radiotherapy induced a DNA damage response (DDR), activated caspase-3, and promoted Tumor Repopulation in NSCLC cells. Unexpectedly, caspase-3 knockout attenuated the ataxia-telangiectasia mutated (ATM)/p53-initiated DDR by decreasing nuclear migration of endonuclease G (EndoG), thereby reducing the growth-promoting effect of irradiated, dying Tumor cells. We also identified p53 as a regulator of the Cox-2/PGE2 axis and its involvement in caspase-3-induced Tumor Repopulation after radiotherapy. In addition, injection of caspase-3 knockout NSCLC cells impaired Tumor growth in a nude mouse model. Our findings reveal that caspase-3 promotes Tumor Repopulation in NSCLC cells by activating DDR and the downstream Cox-2/PGE2 axis. Thus, caspase-3-induced ATM/p53/Cox-2/PGE2 signaling pathway could provide potential therapeutic targets to reduce NSCLC recurrence after radiotherapy.
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Caspase-3 Silencing Attenuates Tumor Repopulation Via Impairing Radiation-Induced DNA Damage Response and Downstream Pathway in Non-Small-Cell Lung Cancer
2020Co-Authors: Minghui Zhao, Jin Cheng, Yanping Gong, Yiwei Wang, Yucui Zhao, Jian-zhu Xie, Yanwei Song, Ruyi Zhao, Yu-lan WangAbstract:Abstract Background: Radiotherapy is an effective treatment on non-small-cell lung cancer (NSCLC). However, radiation-induced dying Tumor cells are postulated to generate potent growth signals to stimulate the Repopulation of adjacent surviving Tumor cells, which may promote Tumor recurrence. We investigated the role of caspase-3-centered molecular mechanism in NSCLC Repopulation after radiotherapy.Methods: The stable caspase-3 knockout (Casp3 KO) NSCLC cells were compared with wild-type cells for growth-promoting effect after radiotherapy using in vitro Repopulation model. Western blotting, quantitative real-time PCR, enzyme-linked immunosorbent assay and luciferase reporter assay were used to identify the possible molecules and pathway. To elucidate the function of caspase-3 in Tumor Repopulation, a series of in vitro assays were performed with Casp3 KO NSCLC cells. Finally, Tumor cell growth rate of Casp3 KO and wild-type Tumor cells in vivo was tested using xenograft Tumor assay and key proteins were further confirmed in Tumor tissues with or without radiotherapy.Results: We found that radiation induced DNA damage response (DDR) and caspase-3 activation, as well as promoted Tumor Repopulation in NSCLC cells. Unexpectedly, depleting caspase-3 significantly attenuated ataxia-telangiectasia mutated kinase (ATM)/p53-mediated DDR via attenuating endonuclease G (EndoG) nuclear migration, thus decreasing the growth-promoting effect of irradiated dying cells. Moreover, we identified p53 as a regulator of the Cox-2/PGE2 axis, which was probably involved in caspase-3-centered Tumor Repopulation after radiotherapy. Additionally, depleting caspase-3 in NSCLC cells showed impaired Tumor growth in nude mice model.Conclusions: Our findings demonstrated that caspase-3 was implicated in Tumor Repopulation and that was accompanied by promoting DDR and downstream Cox-2/PGE2 axis activation in NSCLC cells. This hitherto undescribed signaling pathway mediated by caspase-3 may deepen insight into the radiobiology and provide therapeutic targets to reduce NSCLC recurrence after radiotherapy.
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Necroptosis regulates Tumor Repopulation after radiotherapy via RIP1/RIP3/MLKL/JNK/IL8 pathway.
Journal of experimental & clinical cancer research : CR, 2019Co-Authors: Yiwei Wang, Jin Cheng, Yanping Gong, Minghui Zhao, Yuntao Luo, Yucui Zhao, Jian-zhu Xie, Yu-lan WangAbstract:Tumor cell Repopulation after radiotherapy is a major cause for the Tumor radioresistance and recurrence. This study aims to investigate the underlying mechanism of Tumor Repopulation after radiotherapy, with focus on whether and how necroptosis takes part in this process. Necroptosis after irradiation were examined in vitro and in vivo. And the growth-promoting effect of necroptotic cells was investigated by chemical inhibitors or shRNA against necroptosis associated proteins and genes in in vitro and in vivo Tumor Repopulation models. Downstream relevance factors of necroptosis were identified by western blot and chemiluminescent immunoassays. Finally, the immunohistochemistry staining of identified necroptosis association growth stimulation factor was conducted in human colorectal Tumor specimens to verify the relationship with clinical outcome. Radiation-induced necroptosis depended on activation of RIP1/RIP3/MLKL pathway, and the evidence in vitro and in vivo demonstrated that the inhibition of necroptosis attenuated growth-stimulating effects of irradiated Tumor cells on living Tumor reporter cells. The JNK/IL-8 were identified as downstream molecules of pMLKL during necroptosis, and inhibition of JNK, IL-8 or IL-8 receptor significantly reduced Tumor Repopulation after radiotherapy. Moreover, the high expression of IL-8 was associated with poor clinical prognosis in colorectal cancer patients. Necroptosis associated Tumor Repopulation after radiotherapy depended on activation of RIP1/RIP3/MLKL/JNK/IL-8 pathway. This novel pathway provided new insight into understanding the mechanism of Tumor radioresistance and Repopulation, and MLKL/JNK/IL-8 could be developed as promising targets for blocking Tumor Repopulation to enhance the efficacy of colorectal cancer radiotherapy.
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necroptosis regulates Tumor Repopulation after radiotherapy via rip1 rip3 mlkl jnk il8 pathway
Journal of Experimental & Clinical Cancer Research, 2019Co-Authors: Yiwei Wang, Jin Cheng, Yanping Gong, Minghui Zhao, Yuntao Luo, Yucui Zhao, Jian-zhu Xie, Yu-lan Wang, Ling Tian, Xinjian LiuAbstract:Tumor cell Repopulation after radiotherapy is a major cause for the Tumor radioresistance and recurrence. This study aims to investigate the underlying mechanism of Tumor Repopulation after radiotherapy, with focus on whether and how necroptosis takes part in this process. Necroptosis after irradiation were examined in vitro and in vivo. And the growth-promoting effect of necroptotic cells was investigated by chemical inhibitors or shRNA against necroptosis associated proteins and genes in in vitro and in vivo Tumor Repopulation models. Downstream relevance factors of necroptosis were identified by western blot and chemiluminescent immunoassays. Finally, the immunohistochemistry staining of identified necroptosis association growth stimulation factor was conducted in human colorectal Tumor specimens to verify the relationship with clinical outcome. Radiation-induced necroptosis depended on activation of RIP1/RIP3/MLKL pathway, and the evidence in vitro and in vivo demonstrated that the inhibition of necroptosis attenuated growth-stimulating effects of irradiated Tumor cells on living Tumor reporter cells. The JNK/IL-8 were identified as downstream molecules of pMLKL during necroptosis, and inhibition of JNK, IL-8 or IL-8 receptor significantly reduced Tumor Repopulation after radiotherapy. Moreover, the high expression of IL-8 was associated with poor clinical prognosis in colorectal cancer patients. Necroptosis associated Tumor Repopulation after radiotherapy depended on activation of RIP1/RIP3/MLKL/JNK/IL-8 pathway. This novel pathway provided new insight into understanding the mechanism of Tumor radioresistance and Repopulation, and MLKL/JNK/IL-8 could be developed as promising targets for blocking Tumor Repopulation to enhance the efficacy of colorectal cancer radiotherapy.
