Tissue TGF-β expression following conventional radiotherapy and pulsed low-dose-rate radiation

Meyer, Joshua E.; Finnberg, Niklas; Chen, Lili; Cvetković, D; Wang, Bin; Zhou, Lanlan; Lango, Miriam; Hallman, M.A.; Chang-Ming, C.; El‐Deiry, Wafik S.

doi:10.1080/15384101.2017.1317418

Cited by 25 publications

(18 citation statements)

References 19 publications

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“…6,16,17 In this respect, by using PLDR irradiation, a normal tissue damage could be minimised, and tumour control elevated. 51 Benefits of PLDR irradiation, such as less normal tissue damage, were confirmed in in vivo studies of human orthotopic xenografts in nude mice. 14,15 A limit of the PLDR irradiation is the prolonged radiation delivery of one fraction composed of several pulses, which would lead to a larger burden of medical facilities.…”

Section: Discussionmentioning

confidence: 89%

Pulsed low dose-rate irradiation response in isogenic HNSCC cell lines with different radiosensitivity

Todorović

Prevc

Žakelj

et al. 2020

Radiology and Oncology

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BackgroundManagement of locoregionally recurrent head and neck squamous cell carcinomas (HNSCC) is challenging due to potential radioresistance. Pulsed low-dose rate (PLDR) irradiation exploits phenomena of increased radiosensitivity, low-dose hyperradiosensitivity (LDHRS), and inverse dose-rate effect. The purpose of this study was to evaluate LDHRS and the effect of PLDR irradiation in isogenic HNSCC cells with different radiosensitivity.Materials and methodsCell survival after different irradiation regimens in isogenic parental FaDu and radioresistant FaDu-RR cells was determined by clonogenic assay; post irradiation cell cycle distribution was studied by flow cytometry; the expression of DNA damage signalling genes was assesed by reverse transcription-quantitative PCR.ResultsRadioresistant Fadu-RR cells displayed LDHRS and were more sensitive to PLDR irradiation than parental FaDu cells. In both cell lines, cell cycle was arrested in G2/M phase 5 hours after irradiation. It was restored 24 hours after irradiation in parental, but not in the radioresistant cells, which were arrested in G1-phase. DNA damage signalling genes were under-expressed in radioresistant compared to parental cells. Irradiation increased DNA damage signalling gene expression in radioresistant cells, while in parental cells only few genes were under-expressed.ConclusionsWe demonstrated LDHRS in isogenic radioresistant cells, but not in the parental cells. Survival of LDHRS-positive radioresistant cells after PLDR was significantly reduced. This reduction in cell survival is associated with variations in DNA damage signalling gene expression observed in response to PLDR most likely through different regulation of cell cycle checkpoints.

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Section: Discussionmentioning

confidence: 89%

Pulsed low dose-rate irradiation response in isogenic HNSCC cell lines with different radiosensitivity

Todorović

Prevc

Žakelj

et al. 2020

Radiology and Oncology

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“…Slowing the delivery of radiation may increase sublethal damage repair in normal tissues and has been associated with decreased release of transforming growth factor-ß. 11 , 12 There may also be an increased therapeutic ratio through improved efficacy in tumor control as a result of low-dose hypersensitivity. 13 , 14 , 15 , 16 Here, we present a retrospective study of our outcomes in retreating patients with whole-brain PRDR radiation therapy.…”

Section: Introductionmentioning

confidence: 99%

Outcomes From Whole-Brain Reirradiation Using Pulsed Reduced Dose Rate Radiation Therapy

Burr

Robins

Bayliss

et al. 2020

Advances in Radiation Oncology

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Purpose Recurrent intracranial metastases after whole-brain irradiation pose a clinical challenge owing to the escalating morbidity associated with their treatment. Although stereotactic radiosurgery is increasingly being used, there are still situations in which whole-brain reirradiation (ReRT) continues to be appropriate. Here, we report our experience using whole-brain pulsed reduced dose rate radiation therapy (PRDR), a method that delivers radiation at a slower rate of 0.067 Gy/min to potentially increase sublethal damage repair and decrease toxicity. Methods and Materials Patients undergoing whole-brain ReRT with PRDR from January 1, 2001 to March 2019 were analyzed. The median PRDR ReRT dose was 26 Gy in 2 Gy fractions, resulting in a median total whole-brain dose of 59.5 Gy. Cox regression analysis was used for multivariate analysis. The Kaplan-Meier method was used for overall survival, progression free survival, and to evaluate the ReRT score. Binary logistic regression was employed to evaluate variables associated with rapid death. Results Seventy-five patients were treated with whole-brain PRDR radiation therapy. The median age was 54 (range, 26-72), the median Karnofsky performance status (KPS) was 80, and 86.7% had recursive partitioning analysis scores of 2. Thirty-two patients had over 10 metastases and 11 had leptomeningeal disease. The median overall survival was 4.1 months (range, 0.29-59.5 months) with a 1 year overall survival of 10.4%. Age, KPS, dexamethasone usage, and intracranial disease volume were significantly correlated with overall survival on multivariate analysis. A KPS ≤70 was associated with rapid death after radiation. The prognostic value of the ReRT score was validated. The most common acute toxicities were fatigue (23.1%) and headache (16.9%). Conclusions In this large cohort of patients with advanced intracranial metastases, PRDR achieves acceptable survival and may decrease toxicity associated with ReRT. PRDR is an easily implemented technique and is a viable treatment option for ReRT of brain metastases.

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“…Next, impaired cells provoke the production and release of various inflammatory cytokines, accompanying with macrophages or neutrophils infiltration in lung tissue. In parallel, to protect against cellular injury and death, impaired cells also induce the production and release of proliferative molecules or profibrotic cytokines such as transforming growth factor- β (TGF- β ) [2], connective tissue growth factor (CTGF) [3], and alpha-smooth muscle actin ( α -SMA) [4], leading to fibroblast replication and differentiation of fibroblast into myofibroblast. Finally, myofibroblasts produce an abundance of collagen sedimentation leading to lung fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Cryptotanshinone Ameliorates Radiation-Induced Lung Injury in Rats

Jiang

You

Zhu

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Cryptotanshinone (CTS) was reported to repress a variety of systemic inflammation and alleviate cardiac fibrosis, but it is still unclear whether CTS could prevent radiation-induced lung injury (RILI). Here, we investigated the effects and underlying mechanisms of CTS on a RILI rat model. Our data revealed that CTS could efficiently preserve pulmonary function in RILI rats and reduce early pulmonary inflammation infiltration elicited, along with marked decreased levels of IL-6 and IL-10. Moreover, we found that CTS is superior to prednisone in attenuating collagen deposition and pulmonary fibrosis, in parallel with a marked drop of HYP (a collagen indicator) and α-SMA (a myofibroblast marker). Mechanistically, CTS inhibited profibrotic signals TGF-β1 and NOX-4 expressions, while enhancing the levels of antifibrotic enzyme MMP-1 in lung tissues. It is noteworthy that CTS treatment, in consistent with trichrome staining analysis, exhibited a clear advantage over PND in enhancing MMP-1 levels. However, CTS exhibited little effect on CTGF activation and on COX-2 suppression. Finally, CTS treatment significantly mitigated the radiation-induced activation of CCL3 and its receptor CCR1. In summary, CTS treatment could attenuate RILI, especially pulmonary fibrosis, in rats. The regulation on production and release of inflammatory or fibrotic factors IL-6, IL-10, TGF-β1, NOX-4, and MMP-1, especially MMP-1 and inhibition on CCL3/CCR1 activation, may partly attribute to its attenuating RILI effect.

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Tissue TGF-β expression following conventional radiotherapy and pulsed low-dose-rate radiation

Cited by 25 publications

References 19 publications

Pulsed low dose-rate irradiation response in isogenic HNSCC cell lines with different radiosensitivity

Pulsed low dose-rate irradiation response in isogenic HNSCC cell lines with different radiosensitivity

Outcomes From Whole-Brain Reirradiation Using Pulsed Reduced Dose Rate Radiation Therapy

Cryptotanshinone Ameliorates Radiation-Induced Lung Injury in Rats

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