Radiation Medicine and Protection最新文献

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 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.

Fast neutrons have sufficient energy to liberate recoil protons, alpha particles, and other products when they interact with the nuclei of the target material through scattering and absorption processes. Physical interactions with biological tissues occur mainly with hydrogen nuclei and as the protons interact with the hydrogen in tissues, they create dense ionization chains along their tracks thus depositing energy. Fast neutron therapy was pioneered by Robert Stone in 1938 a few years after the discovery of the neutron. Its main advantage is the limited sensitivity to hypoxia and treatment of slow-growing tumors hence better local control. This is where photon therapy has yet to have much success. Energy deposition by fast neutrons in living tissues is higher than in conventional radiotherapy using mega voltage (MV) photon beams. This higher energy deposition gives fast neutrons a higher relative biological effectiveness (RBE) in dealing with certain tumors. Fast neutrons also have a higher linear energy transfer (LET) and can reach deep-sited tumors better than photon therapy. The main challenge with Fast neutron therapy has been extreme toxicity in late-reacting tissues. Overall, fast neutron therapy holds potential for the treatment of certain tumors by leveraging the unique interaction characteristics of fast neutrons with biological tissues. This review therefore intends to bring this uniqueness to light to enhance the understanding of the radiobiological properties of fast neutrons and the advantages associated with its therapy.

Objective

To investigate the contribution of YWHAZ gene on the radioresistance and metastasis ability of oral squamous cell carcinoma (OSCC) cells.

Methods

The relationship between the expression level of YWHAZ gene and the survival of head and neck squamous cell carcinoma (HNSC) patients was analyzed using Gene Expression Profiling Interactive Analysis (GEPIA) database. A radioresistance cell line (CAL-27R) was constructed by irradiating CAL-27 ​cells with fractional doses. Cell survival was measured by colony formation assay. Cell migration and invasion were detected by transwell assay. The formation of γH2AX foci was detected by immunofluorescence assay. The protein expressions were detected by Western blot assay. In some experiments, CAL-27R cells were effectively transferred with siRNA YWHAZ (siYWHAZ).

Results

GEPIA database showed that the expression level of YWHAZ in HNSC tumors was higher than that in adjacent normal tissues, and the HNSC patients with higher level of YWHAZ had a shorter survival. In vitro experiments demonstrated that the expression of YWHAZ protein in CAL-27 ​cells was lower than HSC-3 ​cells (t ​= ​18.89, P ​< ​0.01) and radioresistant CAL-27R cells (t ​= ​25.70, P ​< ​0.01). Knockdown of YWHAZ gene significantly increased radiation-induced cell killing effect, apoptosis induction, and γH2AX foci formation in CAL-27R and HSC-3 cells. Moreover, siRNA YWHAZ transfection also reduced the invasion and migration abilities of the irradiated CAL-27R [(t ​= ​21.09, P<0.01 (migration); t ​= ​6.16, P<0.05 (invasion)] and HSC-3 ​cells [(t = 34.53, P < 0.001 (migration); t ​= ​4.92, P ​< ​0.05 (invasion)] and attenuated radiation-induced expressions of metastasis-related proteins.

Conclusion

YWHAZ contributes to the radioresistance of oral squamous cells and thus it may applicable to be a potential target for OSCC radiotherapy.

Objective

To explore the potential of computed tomography (CT)-based delta-radiomics in predicting early short-term responses to concurrent chemoradiotherapy for patients with non-small cell lung cancer (NSCLC), in order to determine the optimal time point for the prediction.

Methods

A total of 20 patients with pathologically confirmed NSCLC were prospectively enrolled in this study, who did not receive surgical treatment between February 2021 and February 2022. For each case, a total of 1,210 radiomic features (RFs) were extracted from both planning CT (pCT) images along with each of the subsequent three weeks of CT images. Effective ΔRFs were selected using intra-class correlation coefficient (ICC) analysis, Pearson's correlation, ANOVA test (or Mann-Whitney U-test), and univariate logistic regression. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to evaluate the potential to predict short-term responses of different time points.

Results

Among the 1,210 ΔRFs for 1–3 weeks, 121 common features were retained after processing using ICC analysis and Pearson's correlation. These retained features included 54 and 58 of all time points that differed significantly between the response and non-response groups for the first and third months, respectively (P ​< ​0.05). After univariate logistic regression, 11 and 44 features remained for the first and third months, respectively. Finally, eight ΔRFs (P ​< ​0.05, AUC ​= ​0.77–0.91) that can discriminate short-term responses in both at 1 and 3 months with statistical accuracy were identified.

Conclusion

CT-based delta-radiomics has the potential to provide reasonable biomarkers of short-term responses to concurrent chemoradiotherapy for NSCLC patients, and it can help improve clinical decisions for early treatment adaptation.

FLASH radiotherapy (FLASH-RT) is a new strategy for tumor treatment with an ultra-high dose rate of more than 40 ​Gy/s. Compared with conventional radiotherapy (CONV-RT), FLASH-RT has no different inhibitory effects on tumors but less damage to normal tissues, which is called the “spare” effect. The “spare” effect triggers our exploration of the great prospect of subverting conventional radiotherapy and its intricate mechanisms. Mitochondrial homeostasis, the immune microenvironment, or DNA integrity may potentially represent the primary breakthrough direction in understanding the mechanisms. Concurrently, it is imperative to advance timely clinical translation efforts. Clinical trials of FLASH-RT have progressed to Phase II in both the United States and Switzerland, with current findings suggesting that FLASH-RT achieves comparable efficacy to CONV-RT while mitigating side effects in select cancer cell types. While summarizing the existing FLASH experiments, this paper emphasizes the significance of clinical transformation and the challenges that will be faced and proposes possible solutions.

Nasopharyngeal carcinoma is insidious at onset, prone to lymph node metastasis, and has a high rate of locally advanced disease at initial diagnosis. Radiotherapy combined with chemotherapy is the main treatment for locally advanced nasopharyngeal carcinoma, but local recurrence and distant metastasis often lead to treatment failure, of which radioresistance caused by radiotherapy may be one of the reasons. Targeted therapy can selectively inhibit tumor proliferation and metastasis, and patients can achieve long-term survival benefits with low toxic and side effects. Targeted therapy involves a variety of tumor mechanisms, in which combination with radiotherapy may improve radioresistance and the efficacy of radiotherapy. In this review, the advantages and research progress of targeted therapy combined with radiotherapy for nasopharyngeal carcinoma were discussed.

Esophageal cancer (EC) is a very aggressive disease with most cases diagnosed at advanced stages. Early detection and prognosis prediction are of clinical significance in the optimal management of EC. Genomic and proteomic technologies demonstrated limited efficacy due to the invasive nature and the inherent tumor heterogeneity. Non-invasive radiomics has achieved significant results in tumor characterization, treatment response and survival prediction for various cancers. In this article, the current application of both machine learning and deep learning based radiomics in the diagnosis, prognostic prediction and treatment outcome prediction for patients with EC were reviewed. The current challenges and prospects for the future application of radiomics in EC were also discussed.

With the development of social economy and radiotherapy technique, proton/heavy ion radiotherapy has been applied widely to clinical practices. At present, there are at least 29 hospitals in China at various stages of planning, construction, commissioning or clinical operation of medical proton/heavy ion beam radiotherapy equipment. Compared with common radiotherapy accelerators used in conventional external beam radiotherapy, the proton/heavy ion therapy system has more stringent requirements for quality control so as to achieve an optimum therapeutic effect. In order to protect the health rights of patients undergoing radiotherapy, to facilitate the relevant administrative supervision departments to carry out standard-based approval and routine supervision and to promote the development of related medical undertakings, the standard for testing of quality control for medical proton/heavy ion beam radiotherapy equipment is drafted to fill the gap in this regard in China and even worldwide. The standard contains five indicators and corresponding testing methods for radiological protection and safety and 16 indicators for quality control of equipment performance. The standard is a mandatory standard and is based on the relevant Chinese legal requirements for the testing of radiotherapy equipment, so all the indicators listed in the standard shall be tested. During the drafting of the standard, the opinions from hospitals that are currently using proton/heavy ion medical accelerators for radiotherapy purpose and from the related equipment manufacturers were taken into account. The draft standard was revised with reference to these opinions and the feasibility of the related quality control requirements. The official version of the standard was released on March 7, 2023, and implementation is scheduled to begin on March 1, 2024.

Objective

To investigate the effects and underlying mechanism of 2-hexyl-4-pentynoic acid (HPTA), a derivative of valproic acid (VPA), on radiotherapy in breast cancer.

Methods

MCF7 cells and 7,12-dimethylbenz-[α]-anthracene (DMBA)-induced transformed human normal breast cells (MCF10A–DMBA cells) were irradiated with 8 ​Gy X-rays. For both cells there were four groups: control, valproic acid (VPA)/HPTA, IR, and VPA/HPTA+IR groups. MTT and clonogenic survival assays were performed to assess cell proliferation, and comet assay was performed to evaluate DNA damage. Protein expression of γH2AX, 53BP1, Rad51, and BRCA1 was examined via immunofluorescence and immunoblotting. Cycloheximide chase and ubiquitination experiments were conducted to determine Rad51 ubiquitination. In vivo experiments involved a rat model of DMBA-induced breast cancer, with four fractionated doses of 2 ​Gy. Tumor tissue pathological changes and γH2AX, Rad51, and UCHL3 expression levels were measured by hematoxylin-eosin staining, immunohistochemistry, and immunoblotting.

Results

Compared with the IR group, 15 ​μmol/L HPTA reduced the cell proliferation ability of irradiated MCF7 cells (t=2.16, P<0.05). The VPA/HPTA+IR group exhibited significantly increased DNA double-strand breaks relative to those in the IR group (VPA+IR vs. IR, t=13.37, P<0.05; HPTA+IR vs. IR, t=8.48, P<0.05). Immunofluorescence and immunoblotting experiments demonstrated that the VPA/HPTA+IR group displayed significantly increased cell foci formation, γH2AX and 53BP1 protein expression levels compared to the IR group [(γH2AX: VPA+IR vs. IR, t=8.88, P< 0.05; HPTA+IR vs. IR, t=8.90, P< 0.05), (53BP1, VPA+IR vs. IR, t=5.73, P< 0.05; HPTA+IR vs. IR, t=6.40, P< 0.05)]. Further, Rad51 expression was downregulated (VPA+IR vs. IR, t=3.12, P< 0.05; HPTA+IR vs. IR, t ​= ​2.70, P<0.05), and Rad51 inhibition effectively counteracted HPTA-induced radiosensitization. Ubiquitination detection further verified that HPTA inhibits Rad51 expression via UCHL3-dependent Rad51 deubiquitination. In vivo study results showed that 20 ​mg/kg HPTA significantly enhanced the radiosensitivity of breast tumors in rats by inhibiting Rad51 expression.

Conclusions

HPTA is a highly effective radiosensitizer that enhances the radiotherapeutic efficacy of breast cancer treatment through UCHL3-dependent deubiquitination of Rad51.