Prospective Exploratory Study of the Relationship Between Radiation Pneumonitis and TGF-β1 in Exhaled Breath Condensate

Takahashi, Shigeo; Anada, Masahide; Kinoshita, Toshiro; Nishide, Takamasa; Shibata, Toru

doi:10.21873/invivo.12855

Cited by 4 publications

(2 citation statements)

References 14 publications

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“…Given the clinical data indicate that the TGF-β1 level is increased in the irradiated tumors [ 8 , 27 ], we then wondered if the increased TGF-β1 could augment Tregs infiltration in tumors after irradiation. In line with the previous finding, the irradiation was found to promote more Tregs infiltration in 4T1 tumors than the untreated control (Fig.…”

Section: Resultsmentioning

confidence: 99%

PKC-ζ mediated reduction of the extracellular vesicles-associated TGF-β1 overcomes radiotherapy resistance in breast cancer

et al. 2023

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Background Radiotherapy is widely applied in breast cancer treatment, while radiotherapy resistance is inevitable. TGF-β1 has been considered to be an endogenous factor for the development of radiotherapy resistance. As a large portion of TGF-β1 is secreted in an extracellular vesicles-associated form (TGF-β1EV), particularly in radiated tumors. Thus, the understanding of the regulation mechanisms and the immunosuppressive functions of TGF-β1EV will pave a way for overcoming the radiotherapy resistance in cancer treatment. Methods The superoxide-Zinc-PKC-ζ-TGF-β1EV pathway in breast cancer cells was identified through sequence alignments of different PKC isoforms, speculation and experimental confirmation. A series of functional and molecular studies were performed by quantitative real-time PCR, western blot and flow cytometry analysis. Mice survival and tumor growth were recorded. Student’s t test or two-way ANOVA with correction was used for comparisons of groups. Results The radiotherapy resulted in an increased expression of the intratumoral TGF-β1 and an enhanced infiltration of the Tregs in the breast cancer tissues. The intratumoral TGF-β1 was found mainly in the extracellular vesicles associated form both in the murine breast cancer model and in the human lung cancer tissues. Furthermore, radiation induced more TGF-β1EV secretion and higher percentage of Tregs by promoting the expression and phosphorylation of protein kinase C zeta (PKC-ζ). Importantly, we found that naringenin rather than 1D11 significantly improved radiotherapy efficacy with less side effects. Distinct from TGF-β1 neutralizing antibody 1D11, the mechanism of naringenin was to downregulate the radiation-activated superoxide-Zinc-PKC-ζ-TGF-β1EV pathway. Conclusions The superoxide-zinc-PKC-ζ-TGF-β1EV release pathway was elucidated to induce the accumulation of Tregs, resulting in radiotherapy resistance in the TME. Therefore, targeting PKC-ζ to counteract TGF-β1EV function could represent a novel strategy to overcome radiotherapy resistance in the treatment of breast cancer or other cancers. Trial registration: The using of patient tissues with malignant Non-Small Cell Lung Cancer (NSCLC) was approved by the ethics committees at Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (NCC2022C-702, from June 8th, 2022).

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Section: Resultsmentioning

confidence: 99%

PKC-ζ mediated reduction of the extracellular vesicles-associated TGF-β1 overcomes radiotherapy resistance in breast cancer

et al. 2023

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“…However, because tumour and healthy tissue are adjacents, normal tissue will be affected to some extent. For example, acute complications in skin tissue include arrhythmia, inflammation and scaling, as well as chronic complications such as fibrosis of the skin and underlying muscles [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Radiosensitising effect of iron oxide‐gold nanocomplex for electron beam therapy of melanoma in vivo by magnetic targeting

Mohamadkazem

Neshasteh-Riz

Amini

et al. 2023

IET Nanobiotechnology

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Melanoma is a dangerous type of skin cancer sometimes treated with radiotherapy. However, it induces damage to the surrounding healthy tissue and possibly further away areas. Therefore, it is necessary to give a lower dose to the patient with targeted therapy. In this study, the radio‐sensitising effect of gold‐coated iron oxide nanoparticles on electron beam radiotherapy of a melanoma tumour with magnetic targeting in a mouse model was investigated. Gold‐coated iron oxide nanoparticles were prepared in a steady procedure. The melanoma tumour model was induced in mice. Animals were divided into five groups: (1) normal; (2) melanoma; (3) gold‐coated iron oxide nanoparticles alone; (4) electron beam radiotherapy; (5) electron beam radiotherapy plus gold‐coated iron oxide nanoparticles. The magnet was placed on the tumour site for 2 h. The tumours were then exposed to 6 MeV electron beam radiotherapy for a dose of 8 Gy. Inductively coupled plasma optical emission spectrometry test, hematoxylin and eosin staining, and enzyme‐linked immunosorbent assay blood test were also performed. Gold‐coated iron oxide nanoparticles with magnetic targeting before electron beam radiotherapy reduced the growth of the tumour compared to the control group. Blood tests did not show any significant toxicity. Deposition of nanoparticles was more in the tumour and spleen tissue and to a lesser extent in the liver, kidney, and lung tissues. The synergistic effect of nanoparticles administered by the intraperitoneal route and then concentrated into the tumour area by application of an external permanent magnet, before delivery of the electron beam radiotherapy improved the overall cancer treatment outcome and prevented metal distribution side effects.

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Efficacy study of 6 MeV electron beam in the presence of magnetic iron oxide nanoparticles conjugated to cisplatin on B16F10 cells: an in-vitro study

Garshad,

Shanei,

Hejazi

et al. 2024

Appl. Phys. A

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Prospective Exploratory Study of the Relationship Between Radiation Pneumonitis and TGF-β1 in Exhaled Breath Condensate

Cited by 4 publications

References 14 publications

PKC-ζ mediated reduction of the extracellular vesicles-associated TGF-β1 overcomes radiotherapy resistance in breast cancer

PKC-ζ mediated reduction of the extracellular vesicles-associated TGF-β1 overcomes radiotherapy resistance in breast cancer

Radiosensitising effect of iron oxide‐gold nanocomplex for electron beam therapy of melanoma in vivo by magnetic targeting

Efficacy study of 6 MeV electron beam in the presence of magnetic iron oxide nanoparticles conjugated to cisplatin on B16F10 cells: an in-vitro study

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