BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

AIM:To investigate whether specific small interfering RNA ( siRNA) targeting Toll-like receptor 4 ( TLR4) gene inhibits the proliferation of cervical cancer cell line HeLa through NF-κB signaling pathway and down-regula-tion of Bcl-2 expression.METHODS:Three specific TLR4 siRNAs and 1 negative siRNA were transfected respectively in-to HeLa cells.The expression of TLR4 at mRNA and protein levels was measured by reverse transcription-polymerase chain reaction ( RT-PCR) and Western blotting , respectively .The protein expression of p 65 and Bcl-2 was detected by Western blotting.The cell proliferation was determined by MTT assay and plate colony formation assay .The apoptotic rate of the cells and the cell cycle were analyzed by flow cytometry .RESULTS:In comparison with the other 2 kinds of TLR4 siR-NAs, TLR4-siRNA-003 demonstrated the strongest silencing effect on TLR4 gene expression in the HeLa cells at 48 h after transfection.The expression of TLR4 at mRNA and protein levels was reduced by 62% and 89%, respectively.The pro-tein levels of p65 and Bcl-2 significantly decreased .The growth rate of HeLa cells transfected with TLR 4-siRNA-003 was significantly inhibited .Moreover , the cell apoptotic rate increased significantly and the cell cycle was arrested at G 1 phase as the HeLa cells were transfected with TLR 4-siRNA-003 for 48 h.CONCLUSION:Specific TLR4 siRNA effectively in-hibits the expression of TLR4 and inhibits the proliferation of cervical cancer HeLa cells through NF-κB signaling pathway and down-regulation of Bcl-2 expression, indicating that TLR4 may be a new target for the treatment of cervical cancer .

To evaluate the effect of mobilization of peripheral blood stem cells (PBSC) with high dose cyclophosphamide combination chemotherapy and G-CSF in breast cancer patients, a new mobilization protocol was designed on the basis of standard combination chemotherapy regimen, in which the dose of cyclophosphamide was raised to 2 to 4 times, and G-CSF began to be used at the dose of 150 micro g twice everyday when white blood cell (WBC) decreased below 1.0 x 10(9)/L. PBSC collection was performed while WBC increased over 5.0 x 10(9)/L during bone marrow recovering. The PBSC mobilization protocol was completed in 10 patients, the median nadir of WBC was 0.8 (0.4 - 1.0) x 10(9)/L, the median time of PBSC collection was 2 (2 - 4), the median number of collected CD34(+) cells was 6.43 (1.99 - 8.75) x 10(6)/kg. The results showed that the protocol, high dose cyclophosphamide combination chemotherapy, was an optimal PBSC mobilization regimen in breast cancer patients.