Corrigendum: The risk of heart disease-related death among anaplastic astrocytoma patients after chemotherapy: A SEER population-based analysis.

[This corrects the article DOI: 10.3389/fonc.2022.870843.].

The Risk of Heart Disease-Related Death Among Anaplastic Astrocytoma Patients After Chemotherapy: A SEER Population-Based Analysis.

Background: Despite improved overall survival outcomes, chemotherapy has brought concerns for heart disease-related death (HDRD) among cancer patients. The effect of chemotherapy on the risk of HDRD in anaplastic astrocytoma (AA) patients remains unclear. Methods: We obtained 7,129 AA patients from the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2016. Kaplan-Meier and Cox regression analysis were conducted to evaluate the effect of chemotherapy on the HDRD risk. Based on the competing risk model, we calculated the cumulative incidences of HDRD and non-HDRD and performed univariate and multivariate regression analyses. Then, a 1:1 propensity score matching (PSM) was used to improve the comparability between AA patients with and without chemotherapy. Landmark analysis at 216 and 314 months was employed to minimize immortal time bias. Results: AA patients with chemotherapy were at a lower HDRD risk compared to those patients without chemotherapy (adjusted HR=0.782, 95%CI=0.736-0.83, P<0.001). For competing risk regression analysis, the cumulative incidence of HDRD in non-chemotherapy exceeded HDRD in the chemotherapy group (P<0.001) and multivariable analysis showed a lower HDRD risk in AA patients with chemotherapy (adjusted SHR=0.574, 95%CI=0.331-0.991, P=0.046). In the PSM-after cohort, there were no significant association between chemotherapy and the increased HDRD risk (adjusted SHR=0.595, 95%CI=0.316-1.122, P=0.11). Landmark analysis showed that AA patients who received chemotherapy had better heart disease-specific survival than those in the non-chemotherapy group (P=0.007) at the follow-up time points of 216 months. No difference was found when the follow-up time was more than 216 months. Conclusion: AA patients with chemotherapy are associated with a lower risk of HDRD compared with those without chemotherapy. Our findings may help clinicians make a decision about the management of AA patients and provide new and important evidence for applying chemotherapy in AA patients as the first-line treatment. However, more research is needed to confirm these findings and investigate the correlation of the risk of HDRD with different chemotherapy drugs and doses.

Olodaterol exerts anti-inflammatory effects on COPD airway epithelial cells.

BACKGROUND: Airway inflammation is a key feature of chronic obstructive pulmonary disease (COPD) and inhaled corticosteroids (ICS) remain the main treatment for airway inflammation. Studies have noted the increased efficacy of ICS and long-acting beta 2 agonist (LABA) combination therapy in controlling exacerbations and improving airway inflammation than either monotherapy. Further studies have suggested that LABAs may have inherent anti-inflammatory potential, but this has not been well-studied. OBJECTIVE: We hypothesize that the LABA olodaterol can inhibit airway inflammation resulting from exposure to respiratory syncytial virus (RSV) via its binding receptor, the ß2-adrenergic receptor. METHODS: Human bronchial epithelial brushing from patients with and without COPD were cultured into air-liquid interface (ALI) cultures and treated with or without olodaterol and RSV infection to examine the effect on markers of inflammation including interleukin-8 (IL-8) and mucus secretion. The cell line NCI-H292 was utilized for gene silencing of the ß2-adrenergic receptor via siRNA as well as receptor blocking via ICI 118,551 and butaxamine. RESULTS: At baseline, COPD-ALIs produced greater amounts of IL-8 than control ALIs. Olodaterol reduced RSV-mediated IL-8 secretion in both COPD and control ALIs and also significantly reduced Muc5AC staining in COPD-ALIs infected with RSV. A non-significant reduction was seen in control ALIs. Gene silencing of the ß2-adrenergic receptor in NCI-H292 negated the ability of olodaterol to inhibit IL-8 secretion from both RSV infection and lipopolysaccharide stimulus, as did blocking of the receptor with ICI 118,551 and butaxamine. CONCLUSIONS: Olodaterol exhibits inherent anti-inflammatory properties on the airway epithelium, in addition to its bronchodilation properties, that is mediated through the ß2-adrenergic receptor and independent of ICS usage.

The COX-2 inhibitor Celecoxib enhances the sensitivity of KB/VCR oral cancer cell lines to Vincristine by down-regulating P-glycoprotein expression and function.

Previous studies have indicated that long-term chemotherapy decreases the sensitivity of oral cancer cells to chemotherapeutics while simultaneously increasing resistance to these drugs. COX-2 inhibitors are known to enhance the toxic action of anti-tumor drugs against cancer cells. Using the MTT method, we investigated the influence of the COX-2 selective inhibitor Celecoxib on the proliferation of KB/VCR oral cancer cell lines and analyzed the effect of Celecoxib on the regulation of P-glycoprotein (P-gp) expression and function. Western blot analysis was employed to detect the expression of P-gp, and flow cytometry was used to evaluate P-gp function by detecting the accumulation of the active P-gp functional fluorescence substrate within KB/VCR cells. The results revealed that a low dose of Celecoxib (10 µmol/L) showed no growth inhibitory effects on KB/VCR cell lines. When the concentration of Celecoxib was greater than or equal to 20 µmol/L, the inhibitory effect on KB/VCR cells was significantly enhanced in a time- and dose-dependent manner. The lower dose of Celecoxib (10 µmol/L) significantly enhanced the toxicity of Vincristine (VCR) against KB/VCR cell lines. After the application of Celecoxib plus VCR (10 µmol/L+1.5µmol/L, respectively) treatment for 24, 48 or 72 h, the growth inhibition rates of KB/KBV cells were 37.82 ± 1.60%, 47.84 ± 1.29% and 54.43 ± 2.35%, respectively, which were significantly higher than the rates in the cells treated only with Celecoxib (10 µmol/L) or VCR (1.5 µmol/L) (all P<0.01). P-gp expression levels in KB/KBV cells treated with Celecoxib plus VCR (10 µmol/L+1.5 µmol/L, respectively) were markedly lower than the levels in control cells and those treated with VCR (1.5 µmol/L) (all P<0.01). In addition, the intensity of Rho123 fluorescence of KB/KBV cells in cells treated with Celecoxib plus VCR (10 µmol/L+1.5 µmol/L, respectively) or Celecoxib alone (10 µmol/L) was significantly higher than the intensity observed in control cells and those treated with VCR alone (1.5 µmol/L) (all P<0.01). The underlying mechanism of these phenomena is likely correlated with the down-regulation of the expression and function of P-gp due to Celecoxib, thereby increasing the amount of VCR accumulated in KB/VCR cells.