The Footprint of Exosomes in the Radiation-Induced Bystander Effects

Jokar, Safura; Marques, Inês; Khazaei, Saeedeh; Martins‐Marques, Tânia; Girão, Henrique; Laranjo, Mafalda; Botelho, Maria Filomena

doi:10.3390/bioengineering9060243

Cited by 17 publications

(15 citation statements)

References 149 publications

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“…RIBE-induced exosomes can play positive and negative roles in the cells—ncRNAs and ncRFs in exosomes and EVs can regulate gene expression at the destination cells by either activating defense mechanisms or causing instability, increasing inflammation and preparing cells for malignization events [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

Scatter Irradiation of Rat Brain Triggers Sex- and Brain Region-Specific Changes in the Expression of Non-Coding RNA Fragments

et al. 2022

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Non-coding RNA fragments (ncRFs) are small RNA fragments processed from non-coding RNAs (ncRNAs). ncRFs have various functions and are commonly tissue-specific, and their processing is altered by exposure to stress. Information about ncRFs in the brain is scarce. Recently, we reported the brain region-specific and sex-specific expression of ncRNAs and their processing into ncRFs. Here, we analyzed the expression of ncRFs in the frontal cortex (FC), hippocampus (HIP), and cerebellum (CER) of male and female rats exposed to scatter radiation. We found multiple brain region- and sex-specific changes in response to scatter radiation. Specifically, we observed decreased miRNA expression and the increased expression of ra-ncRNA reads in HIP and CER, as well as an increased number of mtR-NA-associated reads in HIP. We also observed the appearance of sense-intronic ncRNAs—in females, in HIP and FC, and in males, in CER. In this work, we also show that tRNA-GlyGCC and tRNA-GlyCCC are most frequently processed to tRFs, in CER in females, as compared to males. An analysis of the targeted pathways revealed that tRFs and snoRFs in scatter radiation samples mapped to genes in several pathways associated with various neuronal functions. While in HIP and CER these pathways were underrepresented, in FC, they were overrepresented. Such changes may play an important role in pathologies that develop in response to scatter radiation, the effect known as “radio-brain”, and may in part explain the sex-specific differences observed in animals and humans exposed to radiation and scatter radiation.

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Section: Discussionmentioning

confidence: 99%

Scatter Irradiation of Rat Brain Triggers Sex- and Brain Region-Specific Changes in the Expression of Non-Coding RNA Fragments

et al. 2022

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“…The tumor cells are killed by the rays and the cellular contents are released. The contents can activate the immune system in vivo, which can kill metastatic tumor cells [ 20 ]. The researchers who conducted the ACCORD trial reported that the mOS of metastatic PDAC patients treated with FOLFIRINOX was 11 months, which was longer than the mOS of 6 months found in the present study [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

The Effects of Radiotherapy on Pancreatic Ductal Adenocarcinoma in Patients with Liver Metastases

Chen

et al. 2022

Current Oncology

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Background: While radiotherapy has been studied in the treatment of locally advanced pancreatic ductal adenocarcinoma (PDAC), few studies have analyzed the effects of radiotherapy on PDAC in patients with liver metastases. This study aimed to determine whether PDAC patients with liver metastases have improved survival after radiotherapy treatment. Methods: The data of 8535 patients who were diagnosed with PDAC with liver metastases between 2010 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Survival analysis and Cox proportional hazards regression analysis of cancer-specific mortality and overall survival were performed, and propensity score matching (PSM) was used to reduce selection bias. Results: After PSM, the median overall survival (mOS) and median cancer-specific survival (mCSS) in the radiotherapy group were longer than those in the nonradiotherapy group (OS: 6 months vs. 4 months; mCSS: 6 months vs. 5 months, both p < 0.05), respectively. The multivariate analysis showed that cancer-specific mortality rates were higher in the nonradiotherapy group than in the radiotherapy group (HR: 1.174, 95% CI: 1.035–1.333, p = 0.013). The Cox regression analysis according to subgroups showed that the survival benefits (OS and CSS) of radiotherapy were more significant in patients with tumor sizes greater than 4 cm (both p < 0.05). Conclusions: PDAC patients with liver metastases, particularly those with tumor sizes greater than 4 cm, have improved cancer-specific survival (CSS) rates after receiving radiotherapy.

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“…After PSM, the effect of radiotherapy was still obvious. Radiotherapy is expected not only to eliminate local lesions but also to activate the immune system to kill metastatic tumor cells through radiation-induced bystander effects [21]. SBRT has been reported to induce immune-related cell death in pancreatic cancer in both preclinical models and tissue samples from patients [22,23].…”

Section: Prognostic Nomogram Building and Validationmentioning

confidence: 99%

The effects of radiotherapy and prognostic nomogram for pancreatic cancer patients with liver-only metastases

Liu,

Yang,

Peng

et al. 2024

Preprint

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Background: This study aimed to investigate the effect of radiotherapy on pancreatic cancer patients with liver metastasis only, and to establish a prognostic model. Methods: Pancreatic cancer patients with liver-only metastases were obtained from 2010 to 2019 in the Surveillance, Epidemiology, and End Results (SEER) database. Then they were divided into a radiotherapy group and a non-radiotherapy group. Cancer-specific survival (CSS) before and after propensity score matching(PSM) was compared between the two groups. The radiotherapy group was then divided into training and validation cohorts. The prognostic nomogram for 6-, and 12-mouth CSS was constructed based on the training set. In addition, 38 patients were recruited from our hospital as an external validation set. The calibration curves, receiver operating characteristic (ROC) curve, Harrell’s concordance index (C-index), decision curve analysis (DCA), and Kaplan-Meier analysis based on risk stratification were performed to evaluate and verify this model. Results: A total of 17453 patients with hepatic oligometastatic pancreatic cancer were included, of which 622 ( 3.6 % ) received radiotherapy and 16831 ( 96.4 % ) did not. Radiotherapy can significantly prolong survival time [median CSS: 8 months vs 5 months (HR, 0.716; 95%CI=0.655–0.783; p<0.001)]. After PSM, similar results can be obtained [median CSS: 8 months vs 7 months (HR, 0877; 95% CI=0.772–0.997; P=0.045)]. Independent prognostic factors in radiotherapy patients included age, race, histology, N staging, surgery, and chemotherapy. The ROC, C-index and Calibration curves showed good discrimination and calibration. DCA and KM curves further demonstrated the model's clinical applicability. Conclusion: Radiotherapy significantly improves survival compared to non-radiotherapy. Patients younger than 70 years old, non-black, with no lymph node metastasis, primary tumor surgery, and systemic chemotherapy have better prognosis. Finally, we developed and validated a model for prognostication and patient counseling.

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The Footprint of Exosomes in the Radiation-Induced Bystander Effects

Cited by 17 publications

References 149 publications

Scatter Irradiation of Rat Brain Triggers Sex- and Brain Region-Specific Changes in the Expression of Non-Coding RNA Fragments

Scatter Irradiation of Rat Brain Triggers Sex- and Brain Region-Specific Changes in the Expression of Non-Coding RNA Fragments

The Effects of Radiotherapy on Pancreatic Ductal Adenocarcinoma in Patients with Liver Metastases

The effects of radiotherapy and prognostic nomogram for pancreatic cancer patients with liver-only metastases

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