one-step-protocol-for-evaluation-mode-radiation-induced-clonogenic

One-step Protocol for Evaluation of the Mode of Radiation-induced Clonogenic Cell Death by Fluorescence Microscopy

Research on ionizing radiation (IR)-induced clonogenic cell death is important for understanding the effect of IR on malignant tumors and normal tissues. ...

Gunma University Graduate School of Medicine

Plants have evolved efficient defense mechanisms known as priming and synergy, both of which can mobilize defense responses more extensively against successive pathogen invasion or simultaneous stimulation by different signal molecules. However, the mechanisms underlying these phenomena were largely unknown. In the present study, we used cultured rice cells and combination of purified MAMP molecules as a model system to study the mechanisms of these phenomena. We found that the pretreatment of rice cells with a low concentration of bacterial lipopolysaccharide (LPS) apparently primed the defense responses induced by successive N-acetylchitooctaose (GN8) treatment. On the other hand, simultaneous treatment with GN8 and LPS also resulted in the similar enhancement of defense responses observed for the LPS-induced priming, indicating that the synergistic effects of these MAMPs are basically responsible for such enhancement of defense responses, though the effect could be interpreted as "priming" under some experimental conditions. These results also indicate that such a positive crosstalk of signaling cascade downstream of MAMP receptors seems to occur very rapidly, probably at early step(s) of signaling pathway. Comprehensive analysis of phytohormones revealed a specific enhancement of the synthesis of jasmonic acid (JA), both in the LPS pretreatment and also simultaneous treatment, indicating a role of JA in the enhancement of downstream responses.

Positive crosstalk of MAMP signaling pathways in rice cells.

The purpose of this study was to compare carbon ion radiotherapy (C-ion RT) and stereotactic radiotherapy (SBRT) with photon beams for the treatment of hepatocellular carcinoma (HCC), specifically with regard to the dose volume parameters for target coverage and normal tissue sparing.

Dosimetric comparison of carbon ion radiotherapy and stereotactic body radiotherapy with photon beams for the treatment of hepatocellular carcinoma.

Carbon ion radiotherapy shows great potential as a cure for X-ray-resistant tumors. Basic research suggests that the strong cell-killing effect induced by carbon ions is based on their ability to cause complex DNA double-strand breaks (DSBs). However, evidence supporting the formation of complex DSBs in actual patients is lacking. Here, we used advanced high-resolution microscopy with deconvolution to show that complex DSBs are formed in a human tumor clinically treated with carbon ion radiotherapy, but not in a tumor treated with X-ray radiotherapy. Furthermore, analysis using a physics model suggested that the complexity of radiotherapy-induced DSBs is related to linear energy transfer, which is much higher for carbon ion beams than for X-rays. Visualization of complex DSBs in clinical specimens will help us to understand the anti-tumor effects of carbon ion radiotherapy.

Visualization of complex DNA double-strand breaks in a tumor treated with carbon ion radiotherapy.

Hypopharyngeal cancer is relatively rare disease and continues to have a poor prognosis. This study analyzed the efficacy and safety of radiotherapy for stage I-IVB hypopharyngeal cancer.

Clinical Outcomes of Definitive and Postoperative Radiotherapy for Stage I-IVB Hypopharyngeal Cancer.

In cancer therapy today, carbon ion radiotherapy is used mainly as monotherapy, whereas cisplatin is used concomitantly with X-ray radiotherapy. The effectiveness of concomitant carbon ions and cisplatin is unclear. To obtain the information on the mechanisms potentially shared between carbon ions or X-rays and cisplatin, we assessed the correlation of sensitivity to the single treatments. In 20 human cancer cell lines, sensitivity to X-rays strongly correlated with sensitivity to cisplatin, indicating the presence of potentially shared target mechanisms. Interestingly, the correlation of sensitivity to carbon ions and cisplatin was much weaker than that of sensitivity to X-rays and cisplatin, indicating the presence of potentially different target mechanisms between carbon ions and cisplatin. Assessment of clonogenic cell death by 4',6-diamidino-2-phenylindole dihydrochloride staining showed that mitotic catastrophe was more efficiently induced by carbon ions than by the same physical dose of X-rays, while apoptosis and senescence were not. These data indicate that the correlation of sensitivity to carbon ions and cisplatin is weaker than that of sensitivity to X-rays and cisplatin, which are helpful as biological basis to understand the potentially shared mechanism among these treatments. Further investigation is mandatory to elucidate the clinical efficacy of carbon ions and cisplatin combination.

Mitotic catastrophe is a putative mechanism underlying the weak correlation between sensitivity to carbon ions and cisplatin.

To evaluate the efficacy and safety of carbon-ion radiotherapy for non-squamous cell carcinoma of the head and neck, 35 patients were enrolled in this prospective study. The primary end-point was the 3-year local control rate, and the secondary end-points included the 3-year overall survival rate and adverse events. Acute and late adverse events were evaluated according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up time for all patients was 39 months. Thirty-two and three patients received 64.0 Gy (relative biological effectiveness) and 57.6 Gy (relative biological effectiveness) in 16 fractions, respectively. Adenoid cystic carcinoma was dominant (60%). Four patients had local recurrence and five patients died. The 3-year local control and overall survival rates were 93% and 88%, respectively. Acute grade 2-3 radiation mucositis (65%) and dermatitis (31%) was common, which improved immediately with conservative therapy. Late mucositis of grade 2, grade 3, and grade 4 were observed in 11, one, and no patients, respectively. There were no adverse events of grade 5. Carbon-ion radiotherapy achieved excellent local control and overall survival rates for non-squamous cell carcinoma. However, the late mucosal adverse events were not rare, and meticulous treatment planning is required. Trial registration no. UMIN000007886.

Prospective observational study of carbon-ion radiotherapy for non-squamous cell carcinoma of the head and neck.

We aimed to evaluate the relationship between brainstem necrosis and dose-volume histograms in patients with head and neck tumors after carbon-ion radiotherapy.

Dose-volume histogram analysis of brainstem necrosis in head and neck tumors treated using carbon-ion radiotherapy.

To evaluate the safety and efficacy of re-irradiation with carbon-ion radiotherapy (C-ion RT) for lymph node recurrence of gynecological cancers after definitive radiotherapy.

Article	Year
Positive crosstalk of MAMP signaling pathways in rice cells. PloS one\| PubMed ID: 23251660	2012
Dosimetric comparison of carbon ion radiotherapy and stereotactic body radiotherapy with photon beams for the treatment of hepatocellular carcinoma. Radiation oncology (London, England)\| PubMed ID: 26377092	2015
Visualization of complex DNA double-strand breaks in a tumor treated with carbon ion radiotherapy. Scientific reports\| PubMed ID: 26925533	2016
Clinical Outcomes of Definitive and Postoperative Radiotherapy for Stage I-IVB Hypopharyngeal Cancer. Anticancer research\| PubMed ID: 27919985	2016
Mitotic catastrophe is a putative mechanism underlying the weak correlation between sensitivity to carbon ions and cisplatin. Scientific reports\| PubMed ID: 28091564	2017
Prospective observational study of carbon-ion radiotherapy for non-squamous cell carcinoma of the head and neck. Cancer science\| PubMed ID: 28730646	2017
Dose-volume histogram analysis of brainstem necrosis in head and neck tumors treated using carbon-ion radiotherapy. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology\| PubMed ID: 28867558	2017
Clinical Impact of Re-irradiation with Carbon-ion Radiotherapy for Lymph Node Recurrence of Gynecological Cancers. Anticancer research\| PubMed ID: 28982873	2017

Daijiro Kobayashi

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