ObjectiveTo understand the current progress of programmed cell death in the pathogenesis of acute pancreatitis, and to provide reference for the pathogenesis and treatment of acute pancreatitis.MethodThe research progress of acute pancreatitis and programmed cell death in recent years was reviewed by reading relevant literatures at home and abroad in recent years.ResultsProgrammed cell death was defined as controlled cell death performed by intracellular procedures, including apoptosis, autophagy, programmed necrosis, and coronation. The pattern of death of pancreatic acinar cells mainly includes apoptosis and programmed necrosis. Although the pathogenesis of acute pancreatitis had not yet been fully clarified, it was known that through the study of programmed cell death, it could help us to understand the pathogenesis and pathogenesis of acute pancreatitis and provide more effective treatment methods.ConclusionsProgrammed cell death is very important for acute pancreatitis. The mechanism of programmed cell death in acute pancreatitis is necessary for the treatment and prevention of it.
Objective To summarize the research progress of programmed cell death protein 1 (PD-1)/programmed cell death protein-ligand 1 (PD-L1) inhibitors before liver transplantation of liver cancer. Method The literatures on the application of PD-1/PD-L1 inhibitors before liver transplantation of liver cancer were collected and reviewed. Results PD-1/PD-L1 inhibitors preoperatively treated liver transplantation recipients had a low incidence of postoperative rejection, and routine usage of hormone and immune tolerance induction therapy in liver transplantation recipients might reduce the incidence of rejection caused by PD-1/PD-L1 inhibitors. Conclusion Preoperative usage of PD-1/PD-L1 inhibitors have more benefits than risks for patients with advanced liver cancer.
ObjectiveTo explore the clinical value of immunotherapeutic drugs represented by programmed cell death-1 (PD-1) / programmed cell death ligand-1 (PD-L1) blockades for treatment of advanced gastric cancer. MethodThe latest literatures about the clinical studies of PD-1/PD-L1 blockades for the treatment of advanced gastric cancer were retrieved and reviewed. ResultsThe corresponding clinical trials relevant to PD-1/PD-L1 blockades had been conducted in the treatment, biomarkers, and resistance to drugs for advanced gastric cancer. The PD-1/PD-L1 blockades single drug or its in combination with chemical drugs or (and) targeted drugs for the treatment of advanced gastric cancer or gastroesophageal junction cancer had shown a good efficacy in some patients. The patients who benefited from PD-1/PD-L1 blockades might be a population with specific molecular characteristics, but the resistance to drugs during the therapy process affected its therapeutic effect. ConclusionFrom the progress of this review, PD-1/PD-L1 blockades bring benefits to some patients with advanced gastric cancer, but more biomarkers which can predict the therapeutic effect need to be found to optimize the drug regimen, and the resistance to drugs mechanism needs to be further studied.
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.
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 explore the safety and effectiveness of transarterial chemoembolization (TACE) combined with lenvatinib and programmed cell death protein-1 (PD-1) antibody in the conversion resection for intermediate and advanced unresectable hepatocellular carcinoma (HCC), and to provide new treatment strategies for the treatment of intermediate and advanced unresectable HCC. MethodThirty-eight intermediate and advanced unresectable HCC patients treated at West China Hospital of Sichuan University from October 2020 to June 2021 were prospectively included in our study, all patients treated with TACE + lenvatinib + PD-1 antibody, and the clinical data of these 38 patients were summarized. ResultsThe last evaluation time for the 38 patients was October 20, 2021. According to the mRECIST standard for tumor efficacy evaluation, the objective response rate was 84.2% (32/38), the disease control rate was 94.7% (36/38); the conversion success rate based on imaging was 55.3% (21/38), the actual conversion resection rate was 52.6% (20/38). The incidence of adverse events was 100%, of which 22 patients had grade 3 adverse events, and there was no ≥ grade 4 adverse events. All patients were followed up, the follow-up time was 16–52 weeks, and the median follow-up time was 33.5 weeks. During the follow-up period, only two patients had tumor progression, of which one patient died due to disease progression, and there was no postoperative recurrence. ConclusionsLenvatinib combined with TACE and PD-1 antibody is safe for the treatment of intermediate and advanced unresectable HCC. Triple therapy can achieve satisfactory conversion resection rate of intermediate and advanced unresectable HCC, which will provide a new treatment strategy for it.
Objective To examine the association between programmed cell death ligand 1 (PD-L1) expression and venous thromboembolism (VTE) risk in lung cancer patients treated with immune checkpoint inhibitors (ICIs). Methods We enrolled adults with lung cancer who initiated ICIs between January 2018 and March 2022 at West China Hospital of Sichuan University. The included patients were divided into PD-L1 TPS<50% group and PD-L1 TPS≥50% group. Clinical outcomes including VTE, pulmonary embolism (PE), and deep venous thrombosis (DVT) were evaluated with cox regression models. Results Of the 519 lung cancer patients receiving ICIs finnaly analyzed (347 cases with PD-L1 TPS<50%; 172 cases with PD-L1 TPS≥50%), VTE developed in 48 cases (9.2%) during the 12-month follow-up, of which 41 cases (7.9%) had DVT, 4 cases (0.8%) had PE, and 3 cases (0.6%) had DVT and PE. A higher incidence of VTE was observed in TPS<50% group versus TPS≥50% group (P=0.026), whereas there was a trend toward an increased rate of DVT, which was not statistically significant (P=0.052). Significant differences in PE were not found (P=0.152). After multivariable adjustment, PD-L1 TPS<50%, ECOG PS≥2, chronic obstructive pulmonary disease, and VTE history were associated with an increased VTE risk (P<0.05). Conclusion VTE occurred in 9.2% of ICI-treated lung cancer patients. PD-L1 TPS<50% was associated with an increased risk of VTE, which should be identified, prevented and intervened early in clinical practice.
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Although surgery can cure some early-stage resectable patients, the postoperative recurrence rate remains as high as 30%-55%. Perioperative immune checkpoint inhibitor (ICI) therapy, which includes "neoadjuvant" therapy before surgery and "adjuvant" therapy after surgery, has significantly improved survival outcomes in resectable NSCLC patients. Large clinical studies, such as CheckMate 816, have demonstrated the superiority of neoadjuvant ICIs combined with chemotherapy in increasing the pathological complete response rate (pCR) and prolonging event-free survival (EFS). However, even with these advanced treatments, some patients do not achieve long-term benefits and experience early recurrence. This paper reviews the latest research progress of perioperative ICIs in NSCLC treatment, particularly the effectiveness of neoadjuvant chemoimmunotherapy in improving pCR and extending EFS. It further explores the recurrence patterns, resistance mechanisms, and potential biomarkers in NSCLC patients after neoadjuvant immunotherapy. By integrating basic research and clinical data, we analyze the mechanisms of early recurrence following perioperative immunotherapy and discuss future research directions and therapeutic strategies, providing new insights into precision treatment and recurrence prevention for NSCLC patients.
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.