ObjectiveTo summarize the mechanism of action of programmed cell death protein 1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors, the application in breast cancer in recent years and the advances in the study of their bio-markers of effects. MethodRelevant literatures on PD-1/PD-L1 inhibitors and the study in the field of breast cancer were reviewed and summarized.ResultsIn recent years, the monotherapy of immune checkpoint inhibitors represented by PD-1/PD-L1 inhibitors or in combination with other therapies had brought new hope for patients with breast cancer especially triple-negative breast cancer (TNBC). However, only a small number of patients could benefit from breast cancer immunotherapy. The current researchers think that the efficacy of these drugs is related to PD-L1 expression in tumor tissue, tumor mutation burden (TMB), high level of microsatellite instability (MSI-H) and deficient mismatch repair (dMMR).ConclusionBreast cancer can benefit from the immunotherapy of PD-1/PD-L1 inhibitors, but formulating personalized medicine model, finding biomarkers that can predict efficacy and selecting patients with breast cancer who can benefit from it for targeted therapy are the new requirements in the new era of breast cancer immunotherapy.
We reported three cases of stageⅢ/N2 non-small cell lung cancer (NSCLC) treated with neoadjuvant immunotherapy and stereotactic body radiation therapy (SBRT) in our hospital, including 2 males and 1 female with a mean age of 65.7 years. The patients received two doses of the programmed cell death protein-1 inhibitor toripalimab after 1 week of SBRT. Thereafter, surgery was planned 4-6 weeks after the second dose. One patient achieved pathologic complete response, one achieved major pathologic response (MPR), and one did not achieve MPR with 20% residual tumor. There were few side effects of toripalimab combined with SBRT as a neoadjuvant treatment, and the treatment did not cause a delay of surgery.
ObjectiveTo understand the molecular mechanism of ferroptosis and its research progress and future prospects in pancreatic cancer. MethodThe relevant literature on the molecular mechanism of ferroptosis and its basic and clinical application in the occurrence and development of pancreatic cancer was retrievaled and reviewed. ResultsFerroptosis was a non-apoptotic form of cell death that depended on iron aggregation, and its molecular biological features included iron ion overload, reactive oxygen species accumulation, lipid peroxidation, and so on. Ferroptosis was closely related to cell metabolism, and the imbalance of ferroptosis caused by abnormal metabolism also existed during the tumorigenesis and progression of pancreatic cancer, which in turn triggered the abnormal proliferation of pancreatic cancer cells and leaded to their progression. By regulating the key molecular signaling pathways of ferroptosis, it was expected to find new drug targets and therapeutic pathways for pancreatic cancer treatment. The results of ferroptosis-related studies so far had shown the potential for future translational research in the field of pancreatic cancer treatment. ConclusionsThe mechanism of ferroptosis is of great value in pancreatic cancer research. At present, there are still many uncharted areas in the study of ferroptosis, and the molecular mechanisms involved are still poorly understood. In the future, as the study of ferroptosis continues, it is expected to provide new ideas for pancreatic cancer treatment and discover new targets for drug development.
Objective To summarize the research progress of microRNA in acute pancreatitis. Methods By reading the domestic and international literatures published in recent years, to summarize the research progress of microRNA in acute pancreatitis. Results In recent years, researches had found that microRNA could be used as a biomarker for acute pancreatitis to predict and determine the occurrence, development, and complications of acute pancreatitis. MicroRNA could regulate the programmed cell death of acute pancreatitis, and played an important role in the development of inflammation and complications, it also could be used as a therapeutic target for acute pancreatitis. Conclusions MicroRNA plays an important role in the development of acute pancreatitis. Researching the mechanism of microRNA in acute pancreatitis is helpful for the treatment and prevention of acute pancreatitis.
Objective To summarize the effect of lenvatinib + transarterial chemoembolization (TACE) + programmed cell death protein-1 (PD-1) antibody in the treatment of hepatocellular carcinoma with main portal vein tumor thrombus and cavernous transformation. Methods In this study, we reported the clinical data of four patients with hepatocellular carcinoma with main portal vein tumor thrombus and cavernous transformation who received conversion therapy with lenvatinib combined with TACE and PD-1 antibody in West China Hospital. Results Among the four patients, two patients achieved complete response and two achieved partial response; tumor markers were significantly decreased after combination treatment. However, all four patients failed to undergo hepatectomy. ConclusionsLenvatinib + TACE + PD-1 antibody is effective for hepatocellular carcinoma with main portal vein tumor thrombus and cavernous transformation. However, there are still many problems worthy of further discussion.
ObjectiveTo screen long non-coding RNAs (lncRNAs) relevant to programmed cell death (PCD) and construct a nomogram model predicting prognosis of hepatocellular carcinoma (HCC). MethodsThe HCC patients selected from The Cancer Genome Atlas (TCGA) were randomly divided into training set and validation set according to 1∶1 sampling. The lncRNAs relevant to PCD were screened by Pearson correlation analysis, and which associated with overall survival in the training set were screened by univariate Cox proportional hazards regression (abbreviation as “Cox regression”), and then multivariate Cox regression was further used to analyze the prognostic risk factors of HCC patients, and the risk score function model was constructed. According to the median risk score of HCC patients in the training set, the HCC patients in each set were assigned into a high-risk and low-risk, and then the Kaplan-Meier method was used to draw the overall survival curve, and the log-rank test was used to compare the survival between the HCC patients with high-risk and low-risk. At the same time, the area under receiver operating characteristic curve (AUC) was used to evaluate the value of the risk score function model in predicting the 1-, 3-, and 5-year overall survival rates of HCC patients in the training set, validation set, and integral set. Then the nomogram was constructed based on the risk score function model and factors validated in clinic, and its predictive ability for the prognosis of HCC patients was evaluated. ResultsA total of 374 patients with HCC were downloaded from the TCGA, of which 342 had complete clinicopathologic data, including 171 in the training set and 171 in the validation set. Finally, 8 lncRNAs genes relevant to prognosis (AC099850.3, LINC00942, AC040970.1, AC022613.1, AC009403.1, AL355974.2, AC015908.3, AC009283.1) were screened out, and the prognostic risk score function model was established as follows: prognostic risk score=exp1×β1+exp2×β2...+expi×βi (expi was the expression level of target lncRNA, βi was the coefficient of multivariate Cox regression analysis of target lncRNA). According to this prognostic risk score function model, the median risk score was 0.89 in the training set. The patients with low-risk and high-risk were 86 and 85, 86 and 85, 172 and 170 in the training set, validation set, and integral set, respectively. The overall survival curves of HCC patients with low-risk drawn by Kaplan-Meier method were better than those of the HCC patients with high-risk in the training set, validation set, and integral set (P<0.001). The AUCs of the prognostic risk score function model for predicting the 1-, 3-, and 5-year overall survival rates in the training set were 0.814, 0.768, and 0.811, respectively, in the validation set were 0.799, 0.684, and 0.748, respectively, and in the integral set were 0.807, 0.732, and 0.784, respectively. The multivariate Cox regression analysis showed that the prognostic risk score function model was a risk factor affecting the overall survival of patients with HCC [<0.89 points as a reference, RR=1.217, 95%CI (1.151, 1.286), P<0.001]. The AUC (95%CI) of the prognostic risk score function model for predicting the overall survival rate of HCC patients was 0.822 (0.796, 0.873). The AUCs of the nomogram constructed by the prognostic risk score function model in combination with clinicopathologic factors to predict the 1-, 3-, and 5-year overall survival rates were 0.843, 0.839, and 0.834. The calibration curves of the nomogram of 1-, 3-, and 5-year overall survival rates in the training set were close to ideal curve, suggesting that the predicted overall survival rate by the nomogram was more consistent with the actual overall survival rate. ConclusionThe prognostic risk score function model constructed by the lncRNAs relevant to PCD in this study may be a potential marker of prognosis of the patients with HCC, and the nomogram constructed by this model is more effective in predicting the prognosis (overall survival) of patients with HCC.
ObjectiveTo systematically evaluate the expression of programmed cell death receptor 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in esophageal squamous cell carcinoma and its relationship with prognosis.MethodsThe literature from PubMed, EMbase, The Cochrane Library, Web of Science, CNKI and Wanfang data from inception to February 22, 2020 was searched by computer. Data were extracted and the quality of literature was evaluated using RevMan 5.3 software for meta-analysis. Egger's and Begg's tests were used to evaluate publication bias, and Stata 15.1 software was used for sensitivity analysis.Results A total of 16 articles were included, and there were 3 378 patients with esophageal squamous cell carcinoma. The methodological index for nonrandomized studies (MINORS) scores were all 12 points and above. The meta-analysis results showed that the positive expression rates of PD-1 and PD-L1 in tumor cells were 37.8% (190/504) and 41.7% (1 407/3 378), respectively. The positive expression of PD-L1 in tumor immune infiltrating cells was 41.7% (412/987). The overall survival (OS) of the tumor cell with high PD-L1 expression was lower than that with low PD-LI expression (HR=1.30, 95%CI 1.01-1.69, P=0.04). The OS of the tumor immune infiltrating cell with high PD-L1 expression was significantly higher than that with low PD-LI expression (HR=0.65, 95%CI 0.53-0.80, P<0.0001).ConclusionPD-L1 has a high expression rate in esophageal squamous cell carcinoma and is an important factor for the prognosis of esophageal squamous cell carcinoma.
Programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) signaling pathway has been found capable of affecting anti-tumor immune effect in many malignancies in recent years. Patients who are diagnosed with advanced non-small cell lung cancer (NSCLC) have considerable responses after receving inhibitors against PD-1/PD-L1. This paper reviews the clinical progress of PD-1/PD-L1 inhibitors in the treatment of NSCLC.
Objective To investigate the necessity of further surgery for patients with locally advanced esophageal squamous cell carcinoma following treatment with the programmed cell death-1 (PD-1) inhibitor combined with chemotherapy, and to assess its impact on survival. MethodsPatients with stage ⅡA to ⅢB esophageal squamous cell carcinoma who received immunotherapy combined with chemotherapy at our hospital from January 2020 to June 2022 were selected for this study. Based on whether they underwent surgery after receiving PD-1 inhibitor combined with chemotherapy, patients were divided into a surgery group and a non-surgery group. We compared the general clinical data, side effects, clinical complete response rates, progression-free survival (PFS), and overall survival (OS) between the two groups. Results A total of 58 patients were included in the study, comprising 45 males and 13 females, with an average age of (65.5±6.9) years. There were no statistical differences in general clinical data or adverse reactions between the two groups. Univariate analysis revealed that the objective response rate and surgery were significantly associated with PFS (P<0.05). Binary logistic regression analysis showed that surgery was the only independent risk factor for PFS (P=0.003). Kaplan-Meier survival analysis showed that the PFS and OS in the surgery group were significantly higher than those in the non-surgery group (HR=0.13, 95%CI 0.036 to 0.520, P＜0.001; HR=0.17, 95%CI 0.045 to 0.680, P=0.004). ConclusionAfter treatment with the PD-1 inhibitor combined with chemotherapy, patients with locally advanced esophageal squamous cell carcinoma still require surgical intervention to achieve improved PFS and OS.
Objective To analyze the predictive value of serum copeptin, pentraxin 3 (PTX3), and soluble programmed cell death ligand 1 (sPD-L1) for poor prognosis in children with neonatal purulent meningitis. Methods Children with neonatal purulent meningitis admitted to the Department of Pediatrics, the Second Hospital of Handan between September 2020 and February 2023 were selected. According to the Gesell developmental scale score, the children were separated into a good prognosis group and a poor prognosis group. The correlation between serum levels of copeptin, PTX3, sPD-L1 and the prognosis of neonatal purulent meningitis were analyzed using Spearman correlation coefficient. The correlation of serum levels of copeptin, PTX3, and sPD-L1 with white blood cell count (WBC) and procalcitonin (PCT) were analyzed using Pearson correlation analysis. The area under the curve (AUC) of serum copeptin, PTX3, and sPD-L1 in predicting the prognosis of neonatal purulent meningitis were obtained by plotting the receiver operator characteristic curve. The factors affecting the prognosis of neonatal purulent meningitis were analyzed using multiple logistic regression analysis. Results A total of 107 children were included. Among them, 79 cases had good prognosis and 28 cases had poor prognosis. The serum levels of copeptin, PTX3, sPD-L1, WBC and PCT in the poor prognosis group were obviously higher than those in the good prognosis group (P<0.05). The levels of serum copeptin, PTX3, and sPD-L1 were positively correlated with the prognosis, WBC, and PCT of neonatal purulent meningitis (P<0.05). The results of logistic regression analysis showed that copeptin, PTX3, and sPD-L1 were risk factors affecting the prognosis of neonatal purulent meningitis (P<0.05). The AUC for predicting the prognosis of neonatal purulent meningitis with the combination of serum copeptin, PTX3, and sPD-L1 was 0.976, and the combined predictive value of the three was better than predicting separately (P<0.05). Conclusions Copeptin, PTX3, and sPD-L1 are abnormally upregulated in the serum of children with poor prognosis of neonatal purulent meningitis. The combination of the three can improve the predictive value for poor prognosis of neonatal purulent meningitis.