The MAPKAPK2 Pathway Mediates Radiation-Induced Tumor Inflammation And Proliferation In Bladder Cancer

Abstract Purpose Radiotherapy is a commonly used method in the treatment of bladder cancer (BC). Radiation induced immunogenic death (ID) and antitumor immune response are related to the prognosis of radiotherapy. As the most powerful antigen-presenting cell in the body, the role of dendritic cells (DCs) is not very clear. Methods Apoptosis level, cell cycle analysis and expression levels of high mobility group protein 1 (HMGB1), calreticulin (CRT) and heat shock protein 70 (HSP70) were performed for bladder cancer cells after hypofractionated radiotherapy. The effects of the conditioned media on DCs for antitumor immune response activation were studied as well. Results The significantly increased apoptosis level, G2/M phase cell cycle arrest and significantly increased HMGB1, CRT and HSP70 expressions, and increased secretion of CCL5 and CCL21 in the supernatant of bladder cancer cells after hypofractionated radiotherapy. The expression of CD80, CD86, CCR5 and CCR7 on DCs was upregulated in the conditioned media of bladder cancer cells after hypofractionated radiotherapy. Conclusion Hypofractionated radiation blocked the cell cycle of BC cells in the G2/M phase and induced ID occurrence, resulting in DCs immune sensitization, which is of great clinical significance in understanding the radiotherapy of BC and the immunoregulation function of DCs.

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Chloroquine Enhances the Radiosensitivity of Bladder Cancer Cells by Inhibiting Autophagy and Activating Apoptosis

Cellular Physiology and Biochemistry ◽

10.1159/000486222 ◽

2017 ◽

Vol 45 (1) ◽

pp. 54-66 ◽

Cited By ~ 29

Author(s):

Feng Wang ◽

Jinyuan Tang ◽

Pengchao Li ◽

Shuhui Si ◽

Hao Yu ◽

...

Keyword(s):

Bladder Cancer ◽

Western Blot ◽

Cancer Cells ◽

Clonogenic Survival ◽

Strand Break ◽

Cell Counting ◽

Dependent Manner ◽

Bladder Cancer Cells ◽

Radiation Induced

Background/Aims: Chloroquine was formerly used as an anti-malarial agent drug but has now been proven to be useful for various diseases. This study aimed to investigate the radiosensitizing effect of chloroquine in bladder cancer, with an emphasis on autophagy inhibition and apoptosis induction. Methods: Bladder cancer cell lines were irradiated with or without chloroquine. Cell proliferation was determined by a Cell Counting Kit 8 assay. The radiosensitization effect of chloroquine was evaluated by clonogenic survival and progression of xenograft tumors. Cell apoptosis was detected by flow cytometry and western blot. Radiation-induced DNA double strand break was measured by the staining of γ-H2AX. In addition, autophagy was detected by western blot, immunofluorescence staining, and electron microscopy. Results: The treatment with chloroquine alone inhibited the proliferation of bladder cancer cells in a dose-dependent manner. Low cytotoxic concentrations of chloroquine enhanced the radiation sensitivity of bladder cancer cells with a sensitization enhancement ratio of 1.53 and 1.40. Chloroquine also obviously weakened the repair of radiation-induced DNA damage. A combination of radiation and chloroquine enhanced the apoptosis rate of EJ and T24 cells and down-regulated the expression of Bcl-2 while up-regulating the expression of caspase-3. Additionally, the relevant markers of autophagy were obviously increased in the combined group, meaning that chloroquine inhibited autophagy induced by irradiation. Furthermore, subcutaneous xenograft tumors displayed that the combination of radiation and chloroquine could impede tumorigenesis in vivo. Conclusion: In summary, these results provided support that by inhibiting autophagy and activating apoptosis, chloroquine might be a potentially promising radiosensitizer in the radiation therapy of bladder cancer.

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Radiation-Induced Precipitation at Thin Foil Surfaces in Ni-Be Alloys

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100055217 ◽

1982 ◽

Vol 40 ◽

pp. 598-599

Author(s):

T. Mukai ◽

T. E. Mitchell

Keyword(s):

Electron Microscopy ◽

High Voltage ◽

Electron Irradiation ◽

High Vacuum ◽

Thin Foil ◽

Homogeneous Precipitation ◽

High Voltage Electron Microscopy ◽

Voltage Electron ◽

High Voltage Electron ◽

Radiation Induced

Radiation-induced homogeneous precipitation in Ni-Be alloys was recently observed by high voltage electron microscopy. A coupling of interstitial flux with solute Be atoms is responsible for the precipitation. The present investigation further shows that precipitation is also induced at thin foil surfaces by electron irradiation under a high vacuum.

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