Radiotherapy and Oncology, Journal Year: 2025, Volume and Issue: unknown, P. 110823 - 110823
Published: Feb. 1, 2025
Language: Английский
Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)
Published: July 29, 2022
Abstract Radiotherapy (RT) is delivered for purposes of local control, but can also exert systemic effect on remote and non-irradiated tumor deposits, which called abscopal effect. The view RT as a simple treatment has dramatically changed in recent years, it now widely accepted that provoke immune response gives strong rationale the combination immunotherapy (iRT). Nevertheless, several points remain to be addressed such interaction system, identification best schedules with (IO), expansion mechanism amplify iRT. To answer these crucial questions, we roundly summarize underlying showing whole landscape clinical trials attempt identify In consideration rarity effect, propose occurrence induced by radiation promoted 100% molecular genetic level. Furthermore, “radscopal effect” refers using low-dose reprogram microenvironment may overcome resistance Taken together, could regarded trigger antitumor response, help IO used radical added into current standard regimen patients metastatic cancer.
Language: Английский
Citations
379
Respiratory Research, Journal Year: 2024, Volume and Issue: 25(1)
Published: Jan. 13, 2024
Abstract Acute respiratory distress syndrome (ARDS) is a common condition associated with critically ill patients, characterized by bilateral chest radiographical opacities refractory hypoxemia due to noncardiogenic pulmonary edema. Despite significant advances, the mortality of ARDS remains unacceptably high, and there are still no effective targeted pharmacotherapeutic agents. With outbreak coronavirus disease 19 worldwide, has increased correspondingly. Comprehending pathophysiology underlying molecular mechanisms may thus be essential developing therapeutic strategies reducing mortality. To facilitate further understanding its pathogenesis exploring novel therapeutics, this review provides comprehensive information from presents therapeutics. We first describe that involve dysregulated inflammation, alveolar-capillary barrier dysfunction, impaired alveolar fluid clearance oxidative stress. Next, we summarize signaling pathways related above four aspects pathophysiology, along latest research progress. Finally, discuss emerging show exciting promise in ARDS, including several pharmacologic therapies, microRNA-based therapies mesenchymal stromal cell highlighting pathophysiological basis influences on signal transduction for their use.
Language: Английский
Citations
25
Cancer Letters, Journal Year: 2024, Volume and Issue: 587, P. 216651 - 216651
Published: Feb. 10, 2024
Language: Английский
Citations
23
Journal of Experimental & Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 41(1)
Published: Nov. 21, 2022
Radioresistance is the primary cause of nasopharyngeal carcinoma (NPC) treatment failure. Previous studies have focused on deficits in cellular apoptosis as a mechanism for radioresistance; however, additional potential death modes involved modulating radiosensitivity NPC not been explored.Pyroptosis was assessed by phase-contrast imaging, LDH release assays, live cell and Western blotting. In vitro vivo assays were used to investigate function gasdermin E (GSDME) ovarian tumor family deubiquitinase 4 (OTUD4). tissues analyzed using blotting, immunohistochemistry, real-time PCR. The molecular determined immunoprecipitation mass spectrometry.Live imaging revealed that 40-75% irradiation-induced dead cells pyroptotic cells. Furthermore, pyroptosis triggered GSDME, which are cleaved activated caspase-3 intrinsic mitochondrial pathway. Additionally, GSDME significantly downregulated radioresistant specimens. Low expression predictor worse prognosis conferred radioresistance both vivo. Mechanistically, OTUD4 deubiquitinated stabilized enhancing promoting pyroptosis. Clinically, correlated with biopsies, patients low suffered worst radiotherapy response survival.GSDME-dependent critical determinant NPC, modulated via deubiquitinating stabilizing GSDME. These findings reveal promising novel direction suggest therapeutic targets sensitizing radiotherapy.
Language: Английский
Citations
47
Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13
Published: April 26, 2022
The combination of immunotherapy and chemoradiotherapy has become the standard therapeutic strategy for patients with unresected locally advance-stage non-small cell lung cancer (NSCLC) induced treatment-related adverse effects, particularly immune checkpoint inhibitor-related pneumonitis (CIP) radiation (RP). aim this study is to differentiate between CIP RP by pretreatment CT radiomics clinical or radiological parameters.A total 126 NSCLC were enrolled in retrospective divided into training dataset (n =88) validation = 38). A 837 features extracted from regions interest based on parenchyma window images. signature was constructed basis predictive least absolute shrinkage selection operator. logistic regression applied develop a nomogram. Receiver operating characteristics curve area under (AUC) evaluate performance etiology identification.There no significant difference datasets any clinicopathological parameters study. signature, named Rad-score, consisting 11 selected features, potential ability empirical α-binormal-based AUCs 0.891 0.896. These results verified AUC 0.901 0.874, respectively. bilateral changes (p < 0.001) sharp border associated identification RP. nomogram model showed good discrimination (AUC 0.953 0.950) 0.947 0.936).CT-based have values differentiating addition produced superior classifying, which could be useful method improve related decision-making.
Language: Английский
Citations
45
Respiratory Research, Journal Year: 2023, Volume and Issue: 24(1)
Published: Jan. 24, 2023
Abstract Background Radiation-induced lung injury (RILI) is the most common and serious complication of chest radiotherapy. However, reported radioprotective agents usually lead to radiation resistance in tumor cells. The key solving this problem distinguish between response cells normal epithelial damage. Methods RNA-Seq was used recognize potential target alleviating progression RILI as well inhibiting growth. activation NLRP3 inflammasome screened by qRT-PCR, western blotting, immunofluorescence, ELISA. An vivo model vitro conditioned culture were constructed evaluate effect NLRP3/interleukin-1β on fibroblasts activation. ROS, ATP, (NADP) + /NADP(H) level detected explore mechanism macrophages mice deleted role RILI. Moreover, primary extracted validate results obtained from cell lines. Results after depends glycolysis-related reactive oxygen species accumulation. DPYSL4 activated acts a negative regulator process. triggers interleukin-1β secretion, which directly affects fibroblast activation, proliferation, migration, eventually leading fibrosis. Conclusions Our study suggests that essential for radiation-induced injury. These data strongly indicate targeting may be effective reducing clinical settings.
Language: Английский
Citations
27
Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15
Published: Feb. 15, 2024
The advent of immune-checkpoint inhibitors (ICIs) has revolutionized the treatment malignant solid tumors in last decade, producing lasting benefits a subset patients. However, unattended excessive immune responses may lead to immune-related adverse events (irAEs). IrAEs can manifest different organs within body, with pulmonary toxicity commonly referred as checkpoint inhibitor-related pneumonitis (CIP). CIP incidence remains high and is anticipated rise further therapeutic indications for ICIs expand encompass wider range malignancies. diagnosis difficult due large individual differences its pathogenesis severity, severe often leads poor prognosis This review summarizes current state clinical research on incidence, risk factors, predictive biomarkers, diagnosis, CIP, we address future directions prevention accurate prediction CIP.
Language: Английский
Citations
17
Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 163, P. 114808 - 114808
Published: May 3, 2023
Radiotherapy is a prevalent treatment modality for thoracic tumors; however, it can lead to radiation-induced lung injury (RILI), which currently lacks effective interventions. ACT001, prodrug of micheliolide, has demonstrated promising clinical application potential, yet its impact on RILI requires further validation. This study aims investigate the radioprotective effects ACT001 and elucidate underlying mechanism. Sprague-Dawley rats were utilized induce following 20 Gy X-ray chest irradiation, tissue inflammation fibrosis assessed using hematoxylin eosin (H&E) Masson staining. Lung injury, inflammation, oxidative stress markers evaluated employing commercial kits. Pyroptosis-related differentially expressed genes (DEGs) analyzed microarray dataset from Gene Expression Omnibus (GEO) database, their functions hub identified through protein-protein interaction networks. detected via RT-qPCR, western blotting, immunofluorescence, immunohistochemistry. The results that ameliorated RILI, diminished pro-inflammatory cytokine release fibrosis, mitigated activation NLRP3 inflammasome while inhibiting pyroptosis in tissue. In conclusion, our reveals suppress inflammasome-mediated improve suggesting potential as novel protective agent RILI.
Language: Английский
Citations
21
International Journal of Radiation Oncology*Biology*Physics, Journal Year: 2023, Volume and Issue: 116(5), P. 1175 - 1189
Published: Feb. 14, 2023
Although the combination of immunotherapy and radiation therapy to treat various malignancies is rapidly expanding, concerns regarding increased pulmonary toxicities remain. The mechanisms immunotherapy- irradiation-induced lung injury involve a complex interplay cell types signaling pathways, much which remains be elucidated.C57/BL6 mice were treated with single fraction (20 Gy) right or 200 μg anti-Programmed death protein 1 antibody twice week. At 7, 30, 60 days after treatment, tissues obtained for unbiased single-cell RNA sequencing histologic staining. Seurat analysis pipeline, Cellchat, Monocol, Single-Cell rEgulatory Network Inference Clustering used define types, mechanisms, mediators driving pathologic remodeling in response this injury. Reverse transcription polymerase chain reaction, immunofluorescent staining, multiplex immunohistochemistry applied validate key results.Thirty distinct subsets encompassing 75,396 cells identified. A comprehensive investigation cell-cell crosstalk revealed that monokine signals derived from senescent fibroblasts substantially elevated Independent analytical strategies senescence-like subtypes fibroblasts, alveolar epithelial cells, B myeloid immune functionally pathologic, high expression senescence-signature proteins, especially Apolipoprotein E, during response. Senescence markers also irradiated human lines, mouse lines (B3T3 L929), publicly available fibrosis data set.These findings demonstrate accumulation macrophages, primary common mechanism These high-resolution transcriptomic provide novel insights into therapeutic opportunities predict prevent therapy-induced
Language: Английский
Citations
19
Pediatric Research, Journal Year: 2024, Volume and Issue: 95(6), P. 1543 - 1552
Published: Jan. 20, 2024
Language: Английский
Citations
9