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.
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 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.
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 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.
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.
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.
ObjectiveTo explore the short-term efficacy and safety of pembrolizumab combined with chemotherapy in the neoadjuvant treatment of non-small cell lung cancer. MethodsThe clinical data of 11 male patients with non-small cell lung cancer who underwent pembrolizumab combined with neoadjuvant chemotherapy in the Department of Thoracic Surgery, the First Affiliated Hospital of Xi'an Jiaotong University from December 2019 to June 2021 were retrospectively analyzed. The average age of the patients was 52.0-79.0 (62.0±6.9) years. The imaging data and pathological changes before and after neoadjuvant treatment were compared, and adverse reactions during neoadjuvant treatment were recorded. Objective remission rate (ORR) and main pathological remission rate (MPR) and pathological complete remission rate (pCR) were the main observation endpoints. ResultsAfter preoperative neoadjuvant therapy with pembrolizumab combined with platinum or paclitaxel, all patients successfully underwent thoracoscopic radical resection of lung cancer. The ORR was 72.7%, and the MPR was 81.8%. Among them, 45.5% of patients achieved pCR. The main adverse reactions were hypoalbuminemia, decreased appetite and nausea. The mortality rate within 30 days after surgery was 0, and no tumor metastasis was observed. ConclusionPembrolizumab combined with neoadjuvant chemotherapy is safe and feasible to treat non-small cell lung cancer, and the short-term efficacy is beneficial.
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.
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.
