RESUMO
PURPOSE: With the treatment of nasopharyngeal carcinoma (NPC) by PD-1/PD-L1 inhibitors used widely in clinic, it becomes very necessary to anticipate whether patients would benefit from it. We aimed to develop a nomogram to evaluate the efficacy of anti-PD-1/PD-L1 in NPC patients. METHODS: Totally 160 NPC patients were enrolled in the study. Patients were measured before the first PD-1/PD-L1 inhibitors treatment and after 8-12 weeks of immunotherapy by radiological examinations to estimate the effect. The least absolute shrinkage and selection operator (LASSO) logistic regression was used to screen hematological markers and establish a predictive model. The nomogram was internally validated by bootstrap resampling and externally validated. Performance of the model was evaluated using concordance index, calibration curve, decision curve analysis and receiver operation characteristic curve. RESULTS: Patients involved were randomly split into training cohort ang validation cohort. Based on Lasso logistic regression, systemic immune-inflammation index (SII) and ALT to AST ratio (LSR) were selected to establish a predictive model. The C-index of training cohort and validating cohort was 0.745 and 0.760. The calibration curves and decision curves showed the precise predictive ability of this nomogram. The benefit of the model showed in decision curve was better than TNM stage. The area under the curve (AUC) value of training cohort and validation cohort was 0.745 and 0.878, respectively. CONCLUSION: The predictive model helped evaluating efficacy with high accuracy in NPC patients treated with PD-1/PD-L1 inhibitors.
Assuntos
Antígeno B7-H1 , Inibidores de Checkpoint Imunológico , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Nomogramas , Humanos , Masculino , Feminino , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/patologia , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Adulto , Curva ROC , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Idoso , Modelos LogísticosRESUMO
Eleven previously undescribed limonoids, trichisins A-K, including eight structural analogues A-H of trijugin and three H-J mexicanolide derivatives, together with two known mexicanolide derivatives were isolated from the fruits of Heynea trijuga Roxb. ex Sims. The structure determination was based on extensive physical data analyses (NMR, MS), and their basic skeletons and the absolute configurations of trichisins A, B, E, K and trichiconnarone A were assigned via X-ray crystallographic analysis (Cu Kα radiation). The hemiketal motifs in trijugins A, B, and E-G are rare in limonoids. Bioactivity screenings suggested that the trijugin H and mexicanolide-type trichiconnarones A and B limonoids were effective in reversing resistance in MCF-7/DOX cells at a nontoxic concentration of 50⯵M with IC50 values of 12.45, 10.86, and 14.96⯵M, respectively.