Cytokine, chemokine alterations and immune cell infiltration in Radiation-induced lung injury: Implications for prevention and management.

Radiation therapy is one of the primary treatments for thoracic malignancies, with radiation-induced lung injury (RILI) emerging as its most prevalent complication. RILI encompasses early-stage radiation pneumonitis (RP) and the subsequent development of radiation pulmonary fibrosis (RPF). During radiation treatment, not only are tumor cells targeted, but normal tissue cells, including alveolar epithelial cells and vascular endothelial cells, also sustain damage. Within the lungs, ionizing radiation boosts the intracellular levels of reactive oxygen species across various cell types. This elevation precipitates the release of cytokines and chemokines, coupled with the infiltration of inflammatory cells, culminating in the onset of RP. This pulmonary inflammatory response can persist, spanning a duration from several months to years, ultimately progressing to RPF. This review aims to explore the alterations in cytokine and chemokine release and the influx of immune cells post-ionizing radiation exposure in the lungs, offering insights for the prevention and management of RILI.

Activation of Nrf2/ARE pathway by Anisodamine (654-2) for Inhibition of cellular aging and alleviation of Radiation-Induced lung injury.

BACKGROUND: Radiation-induced lung injury (RILI) is a common side effect of thoracic tumor radiotherapy, including early-stage radiation-induced lung injury (RP) and late-stage radiation-induced pulmonary fibrosis (RIPF). Currently, it is urgently needed to clarify the pathogenesis of RILI and find safe and effective RILI treatment methods. Irradiation causes DNA damage and oxidative stress in tissues and cells, induces cellular senescence, and promotes the occurrence and development of RILI. In recent years, Anisodamine (654-2) has shown potential therapeutic value in acute lung injury, acute kidney injury, chlamydial pneumonia, and COVID-19. However, there is currently no research on the mechanism of 654-2-mediated cellular senescence and its preventive and therapeutic effects on RILI. PURPOSE: This study aimed to investigate the protective effect and mechanism of 654-2 on X-ray-induced RILI. METHODS: In vivo experiments involved a mouse RILI model with 18 Gy X-ray irradiation. Mice were divided into control, model, medication (control + 654-2), and treatment (model + 654-2) groups. And mice in medication and treatment groups were intraperitoneal injection of 5 mg/kg 654-2 every other day until being sacrificed at week 6. In vitro experiments used MLE-12 cells irradiated with 16 Gy and divided into control, model, and model + 654-2（2 µM and 10 µM） groups. Various assays were performed to evaluate lung tissue morphology, fibrosis, apoptosis, cytokine expression, cellular senescence, protein expression, and antioxidant capacity. RESULTS: 654-2 mitigated pulmonary pathological damage, inflammation, DNA damage, cellular senescence, and apoptosis in RILI mice and MLE-12 cells. It restored epithelial cell proliferation ability and enhanced antioxidant capacity. Additionally, 654-2 activated the Nrf2/ARE pathway, increased Nrf2 phosphorylation, and upregulated antioxidant gene expression. Inhibition of Nrf2 reversed the effects of 654-2 on ROS production, antioxidant capacity, and cell senescence. CONCLUSION: 654-2 can activate the Nrf2/ARE pathway, enhance cellular antioxidant capacity, and inhibit cellular senescence, thereby exerting a protective effect against RILI.

Systemic immune-inflammation index: A new indicator of predicting 1-, 2-and 3-year disease-free survival of patients with colon cancer.

BACKGROUND: The systemic immune-inflammation index (SII) is a useful prognostic indicator for some types of cancer, but it remains to be elucidated if it is similarly useful for colon cancer. OBJECTIVES: This study aims to investigate the prognostic value of preoperative SII in patients with colon cancer undergoing radical surgery. MATERIAL AND METHODS: The clinical materials of 188 patients with colon cancer who underwent radical surgery from September 1, 2013, to August 31, 2018, in Zhongda Hospital at Southeast University (Nanjing, China) were collected retrospectively. The SII was calculated as platelet count × neutrophil count / lymphocyte count. All patients enrolled in the study were then assigned into 2 different groups according to the median value of SII for comparison of clinical features between the 2 groups. The survival curve was drawn using the Kaplan-Meier method. Univariate and multivariate analysis were performed using the Cox regression model, analyzing the independent risk factors. The independent factors were analyzed with the R software to construct a nomogram of 1-, 2- and 3-year disease-free survival (DFS) after operation. Lastly, a web-based probability calculator was constructed to dynamically predict the possibility of DFS of patients. RESULTS: The SII could significantly predict DFS of patients with colon cancer with the median value of 514.13xs. For DFS, multivariate Cox analysis indicated that age, tumor location, pathological N stage, and preoperative SII level were independent risk factors for patients with colon cancer after radical resection (p < 0.05). A nomogram and a web-based probability calculator were constructed based on these factors. CONCLUSIONS: The preoperative SII level can predict DFS in patients who received radical surgery with colon cancer. The nomogram constructed based on independent risk factors is helpful in predicting DFS of colon cancer patients in clinical practice.

A simple-to-use nomogram for predicting the risk of radiation pneumonitis in patients with thoracic segment esophageal squamous cell carcinoma.

Background: Radiation pneumonitis (RP) is one of the most severe complications of radiotherapy (RT) or concurrent chemoradiotherapy for thoracic segment esophageal squamous cell carcinoma (TSESCC) with delayed diagnose by conventional computed tomography (CT). The study aimed to develop a nomogram to predict the risk of RP early. Methods: Data was collected from 174 patients with clinicopathologically confirmed TSESCC from October 2013 to June 2020. Procalcitonin (PCT), C-reactive protein (CRP), and interleukin-6 (IL-6) levels in serum were dynamically monitored during radiotherapy. Lasso analysis was used for feature screening before multivariate logistic regression analysis to reduce the multicollinearity of variables. A nomogram combined with biological factors and clinical signs for individualized risk assessment and precise prediction of RP was developed and assed the performance with respect to its calibration, discrimination. Results: Of the 174 patients, 30 patients developed RP (grade ≥2) while 144 patients did not. After variable screening by Lasso analysis and logistics multivariate regression analysis, the predictor variables that were finally retained in the nomogram prediction model included IL-6, CRP, and radiotherapy techniques. The model displayed good discrimination with an area under the curve (AUC) of 0.898 (95% CI: 0.849-0.947), with the sensitivity and specificity of 0.967 and of 0.736, respectively. This model also shows good calibration and clinical practical value. In addition, the study provided a web-based version of the dynamic nomogram to facilitate clinical application. Conclusions: The study provides a nomogram model containing IL-6, CRP, RT techniques, which could be conveniently used for individualized prediction of RP in patients with TSESCC during radiotherapy or concurrent chemoradiotherapy.

Expression and clinical significance of B cell translocation gene 2 in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is widely known as a highly fatal cancer, and thus it is important to identify tumor-specific and radiosensitivity-specific markers in ESCC. B cell translocation gene 2 (BTG2) has been considered a novel tumor suppressor gene or radiotherapy sensitivity-associated gene. However, the relationship between BTG2 and ESCC development and radiotherapy sensitivity is uncertain. The present study aims to explore the expression and clinical significance of B cell translocation gene 2 (BTG2) in ESCC by analyzing the RNAseq data from the TCGA and immunohistochemical staining of ESCC samples. We found that the level of BTG2 mRNA was significantly decreased in ESCC patients, and further decreased significantly in radiotherapy resistant patients compared to sensitive patients. The positive expression rate of BTG2 protein was 56.0% (103/184) in 184 ESCC tissue samples and 84.0% (42/50) in normal esophageal mucosal samples, respectively. The positive ratios of BTG2 expression in radiotherapy-sensitive group and radiotherapy resistant group were 57.9% (22/38) and 23.5% (4/17), respectively. Furthermore, the analysis indicates that the expression level of BTG2 significantly correlated with lymph node metastasis and clinical staging in ESCC patients. A multivariate analysis with Cox regression model showed that BTG2 level was an independent risk factor affecting the prognosis of ESCC patients. Above all, the downregulation of BTG2 may be used as a molecular marker to identify and predict ESCC progression and radiosensitivity.

Upregulated Expression of Actin-Like 6A is a Risk Factor Affecting the Prognosis of Pancreatic Cancer.

PURPOSE: Actin-like 6A (ACTL6A), a regulatory subunit of the ATP-dependent chromatin-remodeling complex SWI/SNF, acts as an oncogenic factor. This study is aimed at evaluating the correlation between ACTL6A expression and clinicopathological parameters in pancreatic cancer (PC) patients. METHODS: The differences of Actl6a mRNA expression between PC tissues and normal pancreatic tissues were analyzed in public databases, and ACTL6A expression was then determined and confirmed in 60 paired tissue specimens using immunohistochemistry staining. The association analysis between ACTL6A expression and the clinicopathological characteristics was analyzed, as well as Kaplan-Meier survival analysis. Univariate and multivariate Cox analyses were performed to identify the prognostic factors in the overall survival (OS) of patients with PC. RESULTS: The mRNA expression of Actl6a showed significantly higher in PC compared to normal controls (p < 0.05) from public databases. The score of immunohistochemistry staining further confirmed that ACTL6A expression was significantly upregulated in PC tissues (p < 0.001) through immunohistochemistry staining. High ACTL6A expression was associated with lymphovascular space invasion of PC. Kaplan-Meier analysis revealed that the high expression of ACTL6A was markedly associated with poor OS. Moreover, univariate and multivariate analysis demonstrated that ACTL6A acted as an independent risk factor for PC prognosis. CONCLUSION: ACTL6A is upregulated in PC and acts as a risk factor for poor prognosis in patients with PC, and therefore clinicians could around it design preventive measures and individualized treatment to improve mortality in patients with PC.