Combination of carbon ion beam and gemcitabine causes irreparable DNA damage and death of radioresistant pancreatic cancer stem-like cells<i>in vitro</i>and<i>in vivo</i>

Sai, Sei; Wakai, Toshifumi; Varès, Guillaume; Yamada, Shigeru; Kamijo, Takehiko; Kamada, Tadashi; Shirai, Tomoyuki

doi:10.18632/oncotarget.3584

Cited by 50 publications

(56 citation statements)

References 61 publications

(67 reference statements)

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“…In parallel, carbon-ion irradiation induces apoptosis-related Cytochrome C of triple negative breast CSCs [49]. In a pancreas cell line, heavy-ion irradiation induces irreparable clustered double strand breaks [50]. Data from clonogenic assays performed in our study showed a linear response with increasing doses with a unique alpha component.…”

Section: Discussionmentioning

confidence: 73%

Carbon ion irradiation withstands cancer stem cells' migration/invasion process in Head and Neck Squamous Cell Carcinoma (HNSCC)

et al. 2016

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Cancer Stem Cells (CSCs) in Head and Neck Squamous Cell Carcinoma (HNSCC) have extremely aggressive profile (high migratory and invasive potential). These characteristics can explain their resistance to conventional treatment. Efficacy of photon and carbon ion irradiation with addition of cetuximab (5 nM) is studied on clonogenic death, migration and invasion of two HNSCC populations: SQ20B and SQ20B/CSCs. SQ20B express E-cadherin and overexpress EGFR while SQ20B/CSCs express N-cadherin and low EGFR. Cetuximab strongly inhibits SQ20B proliferation but has no effect on SQ20B/CSCs. 2 Gy photon irradiation enhances migration and invasiveness in both populations (p < 0.05), while cetuximab only stops SQ20B migration (p < 0.005). Carbon irradiation significantly inhibits invasion in both populations (p < 0.05), and the association with cetuximab significantly inhibits invasion in both populations (p < 0.005). These results highlight CSCs characteristics: EGFRLow, cetuximab-resistant, and highly migratory. Carbon ion irradiation appears to be a very promising therapeutic modality counteracting migration/invasion process in both parental cells and CSCs in contrast to photon irradiation.

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Section: Discussionmentioning

confidence: 73%

Carbon ion irradiation withstands cancer stem cells' migration/invasion process in Head and Neck Squamous Cell Carcinoma (HNSCC)

et al. 2016

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“…As compared with photon irradiation, a higher percentage (2.4-fold) of GSCs stained positive for nuclear γ-H2AX 24 hours after carbon ion irradiation, demonstrating residual unrepaired double-strand breaks. Likewise, carbon ion irradiation increased persistent γ-H2AX foci as compared with photon irradiation in putative pancreatic stem cells (32,106). These results indicate that the sensitivity of cancer stem cells to carbon ions might exhibit an impaired capability of GSCs to repair carbon ion-induced DNA double-strand breaks.…”

Section: The Impact Of Carbon Ion Irradiation On Tumor Stem Cells Carmentioning

confidence: 80%

The impact of melatonin and carbon ion irradiation on cancer stem cells

Liu¹,

Reíter²

2017

Nucl Med Biomed Imaging

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Aim: Cancer stem cells (CSCs) exhibited an excessive migratory and invasive potential. Melatonin may inhibit multiple crucial signals associated with tumor stem cell self-renewal, viability, invasiveness, tumor growth, and therapy resistance. Carbon ion irradiation may be a promising therapeutic modality in both non-stem-like and stem-like tumor cells in contrast to photon irradiation. A comprehensive understanding of the mechanisms and molecular pathways associated with invasive properties of CSCs is essential in developing novel treatment options for cancer therapy that target CSCs. Materials and methods:A systematic review of the existing literature was conducted using the following search terms: 'melatonin', 'X-ray irradiation', 'charged particle irradiation', 'carbon ion irradiation', 'cancer stem cells', 'tumor-initiating cells' and 'cancer stem-like cells'. The search used PubMed and spanned the period from January 2000 to December 2016. Conclusion:Cancer stem cells possess the capacity of self-renewal and pluripotency, generating all cells within a tumor, and are responsible for tumor growth, therapy resistance and metastasis. Melatonin attenuated AKT activation, EZH2 S21 phosphorylation, EZH2-STAT3 interactions and altered histone modifications to reduce tumor initiation and propagation of brain tumor stem cells (BTSC). Melatonin increases the efficacy of chemotherapeutic agents, targeting both the tumor bulk and BTSCs through the regulation of the expression and function of the ABCG2/BCRP transporter by inducing the methylation of its promoter. Melatonin treatment induced cell death with ultrastructural characteristics of autophagy. Breast cancer stem cells (BCSCs) are responsive to melatonin treatment by way of reducing the viability and the invasiveness of breast cancer mammospheres as well as regulating the expression of OCT4, N-cadherin and vimentin proteins associated with epithelial mesenchymal transition in BCSCs. Carbon irradiation is effective in brain tumor stem cell (BTSC) elimination with relative biologic effectiveness (RBE) in the range of 1.87-3.44. Carbon ion irradiation may be a promising therapeutic modality because it reduces migration and invasion processes in both head and neck squamous cell carcinoma and cancer stem cells in contrast to photon irradiation. Low LET X-ray irradiation may essentially eradicate the non-stem-like tumor cells, consequently the radioresistant cancer stem-like cell population is obviously enriched. In contrast, carbon ion irradiation may eradicate both non-stemlike and stem-like tumor cells at the same time. Carbon ion irradiation is a promising tool to eradicate putative colon cancer stem-like cells. Further investigation to elucidate the mechanisms and molecular pathways involved in cancer stem cells particularly associated with melatonin and carbon ion irradiation certainly is warranted.

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“…138,139,141 In light of the discussion above about some fraction of human tumor cells having higher RBE values because of DNA repair defects, one might ask whether CSCs have lower proton RBEs. Although the published data are scarce, it has been reported that CSCs may be more effectively killed by carbon ions compared to photons in colon and pancreas cancers both in vitro and in vivo, [142][143][144] and CSCs from colon and breast cancers may be more efficiently eliminated by proton irradiation than photon treatment, at least in vitro. [145][146][147] These latter findings suggest a higher RBE for CSCs and, hence, a potential therapeutic gain with protons over photon irradiations in tumors where CSCs are a significant resistant population.…”

Section: B Novel and Mechanistic Biology Studies To Quantify And Ementioning

confidence: 99%

Report of the AAPM TG‐256 on the relative biological effectiveness of proton beams in radiation therapy

et al. 2019

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The biological effectiveness of proton beams relative to photon beams in radiation therapy has been taken to be 1.1 throughout the history of proton therapy. While potentially appropriate as an average value, actual relative biological effectiveness (RBE) values may differ. This Task Group report outlines the basic concepts of RBE as well as the biophysical interpretation and mathematical concepts. The current knowledge on RBE variations is reviewed and discussed in the context of the current clinical use of RBE and the clinical relevance of RBE variations (with respect to physical as well as biological parameters). The following task group aims were designed to guide the current clinical practice: Assess whether the current clinical practice of using a constant RBE for protons should be revised or maintained. Identifying sites and treatment strategies where variable RBE might be utilized for a clinical benefit. Assess the potential clinical consequences of delivering biologically weighted proton doses based on variable RBE and/or LET models implemented in treatment planning systems. Recommend experiments needed to improve our current understanding of the relationships among in vitro, in vivo, and clinical RBE, and the research required to develop models. Develop recommendations to minimize the effects of uncertainties associated with proton RBE for well‐defined tumor types and critical structures.

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Combination of carbon ion beam and gemcitabine causes irreparable DNA damage and death of radioresistant pancreatic cancer stem-like cellsin vitroandin vivo

Cited by 50 publications

References 61 publications

Carbon ion irradiation withstands cancer stem cells' migration/invasion process in Head and Neck Squamous Cell Carcinoma (HNSCC)

Carbon ion irradiation withstands cancer stem cells' migration/invasion process in Head and Neck Squamous Cell Carcinoma (HNSCC)

The impact of melatonin and carbon ion irradiation on cancer stem cells

Report of the AAPM TG‐256 on the relative biological effectiveness of proton beams in radiation therapy

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