RESUMEN
BACKGROUND: The incidence of checkpoint inhibitor-associated pneumonitis (CIP) in advanced non-small cell lung cancer (NSCLC) has been substantiated through large-scale clinical trials or real-world studies. However, reports on CIP incidence within the context of neoadjuvant immunotherapy for resectable NSCLC remain scarce. This study endeavors to investigate the incidence, risk factors, and outcomes of CIP in patients with resectable NSCLC receiving neoadjuvant immunochemotherapy. METHODS: A retrospective, case-control study was conducted on patients diagnosed with NSCLC stages IIA-IIIB who received neoadjuvant immunochemotherapy between January 2018 and September 2022. Patients were stratified into two groups based on the presence or absence of CIP, facilitating a comparative analysis of clinical characteristics, treatment modalities, physiological indicators, and prognostic outcomes . RESULTS: The study cohort comprised 245 patients, with 11.4% (28/245) experiencing CIP. The median period of CIP onset was 70 (range, 40-221) days. The incidence of severe CIP (grade 3-4) was 3.7% (9/245). Patients with CIP showed a higher all-cause mortality rate of 21.4% (6/28) compared to that of patients without CIP. Those who developed CIP exhibited elevated body mass index (BMI) values (p = 0.028) and increased fibrinogen (FIB) levels (p < 0.001), alongside a significant decrease in both diffusing capacity for carbon monoxide (DLCO)% pred (p = 0.001) and DLCO/VA% pred (p = 0.021) after neoadjuvant therapy compared to pre-indicators. Receiver operating characteristic curve (ROC) analysis showed that the area under the ROC curve of three assessed variables (FIB levels, BMI, DLCO) reached 0.806 in predicting CIP occurrence at an early stage. CONCLUSIONS: This cohort demonstrated that elevated BMI, increased FIB levels, and decreased pulmonary diffusion function after neoadjuvant therapy are risk factors of CIP occurrence. Early assessment and continuous monitoring of these indicators are imperative for the predictive identification of CIP, enhancing patient management and outcomes.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Inhibidores de Puntos de Control Inmunológico , Terapia Neoadyuvante , Neumonía , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/terapia , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neumonía/inducido químicamente , Neumonía/epidemiología , Terapia Neoadyuvante/efectos adversos , Estudios Retrospectivos , Estudios de Casos y Controles , Factores de Riesgo , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estimación de Kaplan-Meier , Incidencia , ComorbilidadRESUMEN
BACKGROUND: In order to improve survival outcomes in resectable non-small cell lung cancer (NSCLC), strategies for neoadjuvant therapy need to be revisited. We evaluated and compared the efficacy of different neoadjuvant therapeutic modalities in a real-world setting. METHODS: A total of 258 patients with clinical stage IIA to IIIB NSCLC was included. All the patients underwent surgical resection after one to four cycles of neoadjuvant treatment consisting of chemotherapy (83), immunotherapy (23), and immunotherapy plus chemotherapy (152). RESULTS: The radiologic response rate in the combined immunochemotherapy group was 67.8%, higher than that of 48.2% in the chemotherapy group and 4.3% in the immunotherapy group (p < 0.001). An improved major pathological response (MPR) was also achieved in the combined therapy group compared with the chemotherapy group and the immunotherapy group (53.9% vs. 10.8% vs. 8.7%, p < 0.001). Patients in the combined therapy group had a significant trend toward longer disease-free survival than those in the chemotherapy alone group (3-year disease-free survival [DFS] of 68.79% vs. 50.81%; hazard ratio [HR] for progression or death, 0.477; p = 0.003). Multivariate Cox analysis identified radical surgery (HR, 0.328; p = 0.033), ypN0-1 stage (HR, 0.591; p = 0.038) and MPR result (HR, 0.362; p = 0.007) to be independent prognostic factors for DFS. CONCLUSIONS: Neoadjuvant treatment with a combination of immunotherapy plus chemotherapy appears to achieve higher radiological and pathological responses than monotherapy for IIA-IIIB NSCLC. Log-rank analysis showed that a better outcome could be expected in patients with the addition of immunotherapy to neoadjuvant chemotherapy if compared with patients with chemotherapy alone in terms of DFS.
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Carcinoma de Pulmón de Células no Pequeñas , Inmunoterapia , Neoplasias Pulmonares , Terapia Neoadyuvante , Humanos , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Terapia Neoadyuvante/métodos , Masculino , Femenino , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/tratamiento farmacológico , Persona de Mediana Edad , Anciano , Inmunoterapia/métodos , Estadificación de Neoplasias , Resultado del Tratamiento , Estudios Retrospectivos , Neumonectomía/métodos , Supervivencia sin Enfermedad , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Background/aim: Curcumin may have potential as a therapy for wound healing, but the underlying mechanism remains unclear. It is not known whether curcumin can promote wound healing by activating Nrf2 signaling pathway and inducing apoptosis. This study determined the role of Nrf2 signaling pathway and apoptosis in curcumin-promoting skin wound healing. Materials and methods: The full-thickness skin defect model of mice was made and randomly divided into a control group and a curcumin group. The mice in the curcumin group and in the control group received respectively a daily topical treatment of Vaseline cream with or without 5 mg curcumin. The wound healing of mice was observed daily. The mice in two groups were killed respectively on postinjury days 3, 7, and 14, and the wound tissues were collected, with 5 mice in each group. Pathological change and formation of collagen fibers were observed by HE and Masson staining respectively. The expression of caspase-3 was observed by immunohistochemistry. Western blot was used to examine the protein levels of Nrf2 and HO-1, and ELISA assay and colorimetry assay were used to check the contents of ROS, MDA, SOD, and GSH. Results: The wound healing rates of curcumin group were higher than those of control group (p < 0.05), and the pathological changes were also significantly better than those in the control group (p < 0.05). Collagen fiber synthesis in curcumin group was higher than that in control group (p < 0.05). Moreover, the expression of caspase-3 in curcumin group was higher than that in control group on 7th day post wound (p < 0.05). Furthermore, the levels of ROS and MDA in curcumin were lower than those in control group (p < 0.05), and the level of Nrf2, HO-1, SOD and GSH were higher than those in control group (p < 0.05). Conclusion: Curcumin improves skin wound healing by activating the Nrf2 signaling pathway and inducing apoptosis in mice.
Asunto(s)
Apoptosis , Curcumina , Factor 2 Relacionado con NF-E2 , Transducción de Señal , Piel , Cicatrización de Heridas , Animales , Curcumina/farmacología , Cicatrización de Heridas/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Apoptosis/efectos de los fármacos , Ratones , Transducción de Señal/efectos de los fármacos , Piel/efectos de los fármacos , Piel/metabolismo , Piel/lesiones , Masculino , Modelos Animales de EnfermedadRESUMEN
The present study aimed to investigate the interaction between T-cell immunoglobulin and mucin-domain-containing molecule-3 (Tim-3) and Toll-like receptor 4 (TLR4)/nuclear factor κB (NFκB) signaling in Helicobacter pylori-infected RAW264.7 macrophage cells. RAW264.7 cells were cocultured with H. pylori SS1 at different bacteria/cell ratios, and subsequently the mRNA expression of Tim3, TLR4, and myeloid differentiation factor 88 (MyD88) was measured by reverse transcription-quantitative polymerase chain reaction (RTqPCR). Furthermore, the effect of Tim3 overexpression was examined by transfection of RAW264.7 with pLVX-IRES-ZsGreen-Tim-3 and coculturing with H. pylori. mRNA and protein expression levels were then analyzed for Tim3, TLR4, MyD88, and phosphorylated (p) NFκB by RTqPCR and western blot analysis respectively. The concentrations of proinflammatory cytokines [tumor necrosis factorα (TNFα), interleukin 6 (IL-6), interferonγ (IFNγ) and interleukin 10 (IL10)] released in the culture supernatants were measured by ELISA. H. pylori stimulation resulted in a significant increase of Tim3, TLR4, and MyD88 mRNA expression in RAW264.7 cells. H. pylori stimulation upregulated Tim3 expression even in the Tim3overexpressing RAW264.7 cells compared with unstimulated cells. TLR4, MyD88, and pNFκB protein expression and proinflammatory cytokines (TNFα, IL6, and IFNγ) release levels were increased in the control RAW264.7 cells following H. pylori infection, but not in the Tim-3-overexpressing RAW264.7 cells. By contrast, IL10 levels were decreased following H. pylori infection in both control and Tim3overexpressing RAW264.7 cells. Overexpression of Tim-3 reduced H. pylori-associated inflammation in RAW264.7 macrophages, by downregulating expression of proteins in the TLR4 pathway and release of proinflammatory cytokines. These findings suggest that Tim3 serves a crucial role in the negative regulation of H. pylori-associated inflammation and may be a novel therapeutic target for H. pylori infection.