Radiation Medicine and Protection最新文献

Breast cancer is the most frequently diagnosed malignant tumor in women worldwide and the leading cause of cancer death. Radiotherapy for breast cancer is readily accepted and widely used in clinical practice. Potential limitations with radiotherapy include treatment resistance, side effects, and complications caused by high doses of irradiation. The search has been on to locate an efficacious radiosensitizer. This review summarizes six currently approved pharmaceuticals that have also been investigated for off-label use as radiosensitizers in breast cancer.

Objective

To investigate the role and the molecular mechanisms of apoptotic signaling in ferroptosis to regulate tumor radiosensitivity.

Methods

Reactive oxygen species (ROS) and lipid peroxide levels were detected in Mouse embryonic fibroblasts(MEFs) with Bcl-xL or Mcl-1 deficiency induced by erastin. Colony formation, ROS, lipid peroxidation and the transcription/translation levels of PTGS2 were measured in Bcl-xL knockdown tumor cells induced by 5 ​Gy γ-rays or co-treated with ferrostatin-1 (Ferr-1). The protein levels of LPCAT3, ACSL4 and PEBP1 in Bcl-xL knockout MEF cells were evaluated in Bcl-xL knockout MEF cells post-radiation. Moreover, the interaction of heat shock protein 90 (HSP90) with Bcl-xL, GPX4, or LAMP2A was detected by protein mass spectrometry and immunoprecipitation assays.

Results

Manipulating Bcl-xL levels facilitated radiation-induced ferroptosis by augmenting the enzymatic oxidation of polyunsaturated fatty acids (PUFAs) and enhancing chaperone-mediated autophagy (CMA) of glutathione peroxidase 4 (GPX4) (MEF cell line: t=4.540, P＜0.01; A549 ​cell line: t=56.16, P＜0.0001; t=4.885, P＜0.01; HCT116 ​cell line: t=14.75, P＜0.01; t=7.363, P＜0.05). Downregulating Bcl-xL expression promoted the activity of acyl-CoA synthetase long-chain family member 4 (ACSL4), thus increasing the enzymatic oxidation of PUFAs (t=4.258, P＜0.01). Moreover, depletion of Bcl-xL expedited the CMA process targeting GPX4 by facilitating the association of GPX4 with heat shock protein 90 (HSP90) and LAMP2A following radiation exposure. Subsequent degradation of GPX4 led to the accumulation of lipid peroxides, ultimately triggering ferroptosis.

Conclusions

Our study provides initial insights into the regulatory role of Bcl-xL in ferroptosis and underscores the potential of targeting Bcl-xL as a promising therapeutic strategy for cancer by modulating both apoptotic and ferroptotic pathways.

Objective

To validate the safety and efficacy of chronochemotherapy for locoregionally advanced nasopharyngeal carcinoma (NPC).

Methods

Participants for this phase II randomized controlled trial were recruited from the Department of Head and Neck Oncology at the Affiliated Cancer Hospital of Guizhou Medical University. Patients enrolled (128 in total, 112 in the final analysis) between April 1, 2017, and February 28, 2018, were randomly divided into the chronochemotherapy and conventional chemotherapy groups. In the chronochemotherapy group, docetaxel was intravenously administered between 3:30 a.m. and 4:30 a.m. on day 1, followed by intravenous administration of cisplatin between 10:00 a.m. and 10:00 p.m. from day 1to day 5. In addition, 5-fluorouracil was administered through a continuous intravenous pump between 10:00 p.m. and 10:00 a.m. (2nd day) from day 1 to day 5. In the conventional chemotherapy group, docetaxel (on day 1), cisplatin (on day 2), and 5-fluorouracil (from day 1 to day 5, 120 ​h in total) were administered without time-specific constraints. Both groups underwent intensity-modulated radiation therapy with 6-MV X-rays. The gross target volume (GTV) comprised the nasopharyngeal GTV and cervical lymph node GTV. The primary endpoint was immune function, quantified by measuring dendritic cell and lymphocyte subsets, whereas the secondary endpoints were therapeutic efficacy and incidence of adverse events. Pearson Chi-square test was applied to compare total events between the groups, Mann-Whitney U test was used to compare the DC subsets and toxicities, and Wilcoxon signed-rank test ​was used to compare the continuous variables between the two groups.

Results

Chronochemotherapy preserved immune function, as evidenced by elevated levels of myeloid dendritic cells (P ​= ​0.394) and higher CD4/CD8 ratio (P ​= ​0.781). No significant difference in overall response rate, measured as the sum of complete and partial response rates, was observed between the groups (P ​= ​0.711). A reduction in the incidence of vomiting (P ​= ​0.002), stomatitis (P ​= ​0.028), and mucositis (P ​= ​0.028) was observed in the chronochemotherapy group. Leukopenia incidence rate was 83.3 ​% and 92.3 ​% in the chronochemotherapy and conventional chemotherapy groups, respectively (P ​= ​0.232).

Conclusions

In patients with locoregionally advanced NPC, the overall response rate of chronochemotherapy is comparable to that of conventional chemotherapy; however, chronochemotherapy shows fewer adverse events.

Objective

To evaluate the effectiveness of a portable thyroid radioiodine meter in on-site monitoring to enhance the monitoring precision of radioiodine inhaled by nuclear medicine staff and patients.

Methods

A portable thyroid radioiodine meter was developed to measure the ¹³¹I activity in the thyroid. Performance tests of the portable thyroid radioiodine meter were conducted using calibration sources and testing methodologies adhering to national metrological standards.

Results

The thyroid radioiodine meter exhibited integral non-linearity, 8-h measurement stability, measurement linearity, and an energy resolution of 0.42%, 1.05%, 1.56%, and 7.11%, respectively for ¹³⁷Cs at 661.66 ​keV. Additionally, its minimum detectable activity for ¹³¹I at 364.49 ​keV was approximately 22 Bq (10 ​min).

Conclusion

The developed thyroid radioiodine meter features elevated performance and great potential for application in nuclear medicine and monitoring of responses to nuclear or radiological emergencies.

Objective

To explore the reduction effect for the indoor ²²²Rn (Rn) by Fresh Air Ventilation (FAV) system, a novel commercial ventilation device in China.

Methods

The indoor concentrations of Rn and its decay products (RnD) in three residential rooms, two in Beijing and one in Hefei city, Anhui province, before and after FAVS functioned were measured using an active continuous method. The air exchange rate was monitored by measuring CO₂ concentration using the tracer gas method.

Results

In the three rooms, the FAVS reduced the Rn concentrations from (162 ​± ​80) Bq/m³ to (63 ​± ​22) Bq/m³ and decreased the RnD concentrations from (64 ​± ​35) Bq/m³ to (13 ​± ​6) Bq/m³ on average, a decrease of (59 ​± ​25)% in the Rn concentrations and a drop of (77 ​± ​18)% in the RnD concentrations. Considering dose conversion factors of Rn and RnD, FAVS decreased the exposure dose by (76 ​± ​20)%. Besides, FAVS increased the air exchange rates from 0.17 h⁻¹ to 0.56 h⁻¹ on average.

Conclusions

FAVS can effectively reduce indoor Rn and RnD concentrations by improving the air exchange, serving as a valuable supplement to existing radon mitigation methods, especially in extreme climates.

The annex A of the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) 2020/2021 Report presented a comprehensive global estimate of frequencies and doses from medical exposure to ionizing radiation, their distribution and trends for the period 2009–2018. The annex considered four general categories of medical practice using ionizing radiation: (a) diagnostic radiology, including dental radiology and computed tomography, (b) interventional radiology (image-guided interventional procedures), (c) nuclear medicine, and (d) radiation therapy. In the period 2009–2018, about 4.2 billion medical radiological examinations were performed annually, resulting in an annual effective dose of 0.57 ​mSv per caput. The use of computed tomography has continued to grow and the contribution from interventional radiology has increased rapidly in recent years. The annual number of radionuclide therapy treatments has increased by 60% since the UNSCEAR 2008 Report, while the number of courses of radiation therapy has increased by 22%. Medical exposure remains by far the largest human-made source of radiation exposure to the public. The Committee's evaluation relies on the collection of up-to-date and representative exposure data from all Member States of the United Nations. Future exposure survey should be more relevant and useful and adapted to changing data sources and changing uses of radiation across the world.

Objective

To formulate an efficacious radioprotective combination of Chinese medicines with minimal toxicity.

Methods

Aqueous and alcoholic extracts from 38 traditional Chinese herbs were prepared. To produce drug-containing sera, rats received six doses of each extract via oral gavage at 12-h intervals. Subsequently, human lung epithelial BEAS-2B cells were cultured in these drug-containing sera. The cell viability was assessed after different doses of irradiation to identify the radioprotective effects of Chinese herbal extracts. The efficacy of a selected Chinese herbal extract combination was further confirmed through cell viability analysis via in vitro colony formation and survival rate assessments in C57BL/6 mice post-irradiation.

Results

Extracts from Angelicae Sinensis Radix (ASR; two extracts), Citri Reticulatae Pericarpium (CRP), Platycladi Cacumen (PC), Schisandrae chinensis Fructus (SF), Scutellariae Radix (SR), and Glycyrrhizae Radix et Rhizome (GRR) demonstrated radioprotective effects. The combination of the seven Chinese herbal extracts notably increased the survival and viability of the BEAS-2B cells exposed to varying doses of X-rays. Moreover, the group of mice receiving Chinese medicine combination and irradiation exhibited prolonged survival after exposure to 6.5 ​Gy X-rays with a median survival of （14 ​± ​2）d compared to （11 ​± ​2）d in the irradiated group without the herbal treatment. Additionally, the Chinese medicine combination group displayed a significantly higher 28 ​d survival rate (30%) compared to the irradiation-only group (16.6%, P ​< ​0.05).

Conclusion

The novel combination of Chinese herbal extracts from ASR, CRP, PC, SF, SR, and GRR has the potential for radiation protection applications.

The hematopoietic system is susceptible to ionizing radiation (IR), which can cause acute hematopoietic failure or long-term myelosuppression. As the most primitive cells of the hematopoietic hierarchy, hematopoietic stem cells (HSCs) maintain lifelong hematopoietic homeostasis and promote hematopoietic regeneration during stress. Numerous studies have shown that nuclear and mitochondrial genomes are the main targets of radiation injury in HSCs. More importantly, the damage of DNA may trigger a series of biological responses that largely determine HSC fate following IR exposure. Although some essential pathways and factors involved in DNA injury and damage in HSCs have been revealed, a comprehensive understanding of the biological effects of radiation on HSCs still needs to be improved. This review focuses on recent insights into the molecular mechanisms underlying DNA damage and repair in HSCs after IR. Then summarize corresponding regulatory measures, which may provide a reference for further research in this field.

The annex D of the United Nations Scientific Committee on the Effects of Atomic Radiation （UNSCEAR） 2020/2021 Report presented a comprehensive global estimate of occupational exposure to ionizing radiation. The worldwide annual number of workers exposed to natural and human-made sources of ionizing radiation was estimated to be approximately 24 million in the period 2010–2014. About 52% of those were employed in the sectors that involve exposure to natural sources of radiation. The worldwide average annual effective dose for all workers during the period 2010–2014 was estimated to be around 1.2 ​mSv – about two thirds of the value estimated for the period 1995–1999. The annual effective dose was estimated to be around 2.0 ​mSv for workers exposed to natural sources and 0.5 ​mSv for workers exposed to human-made sources. The overriding limitation of current evaluation was the low rate of participation by United Nations Member States in providing occupational exposure monitoring data, especially data from non-nuclear sectors and occupational sectors involving naturally occurring radioactive materials. As the assessment of the worldwide occupational exposure is a complex task, the Committee relies on the collection of up-to-date data on occupational exposure from United Nations Member States in a broad range of occupational sectors, and continues collaboration with international organizations.

The concept of low-dose radiation (LDR)-induced hormetic responses was initially observed approximately 70 years ago and systematically reviewed along with the discovery of LDR-induced adaptive responses in a cytogenetic in vitro study in 1980s. By the end of the 1990s, discussions regarding the potential applications of LDR-induced hormesis and adaptive responses for preventing or treating chronic diseases, such as Alzheimer’s disease (AD) had taken place. Until 2016, reports on radiotherapy for the subjects with AD and for genetic AD model mice were published. Subsequently, several preclinical studies with animal models of AD and clinical studies in AD subjects were conducted. A significant milestone was achieved with the online availability of a new Systematic Review based on qualified publications from these preclinical and clinical studies. This mini-review provides a concise historical introduction to LDR-induced hormesis and adaptive responses with discussion of AD radiotherapy with either LDR or relatively high dose radiation. Highlights of this Systematic Review cover promising outcomes, challenges, and new questions, followed by discussion of potential mechanisms.