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.
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.
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.
Neuropathic pain (NP) is a pathological state caused by damage or disease to the somatosensory nervous system. Programmed cell death (PCD) is an orderly process of cell death regulated by both intrinsic signals and external stimuli. In recent years, an increasing number of studies have shown that PCD plays a key regulatory role in the pathogenesis of NP. This article reviews the molecular mechanisms of various types of PCD and their specific roles in NP, in order to provide new research directions for the prevention, diagnosis, and treatment of NP.
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.
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 detect the expression of programmed cell death ligand 1 (PD-L1) in papillary thyroid carcinoma (PTC) and PTC with coexistent Hashimoto’s thyroiditis (HT) tissues, and to explore its clinical significance of its expression.MethodsThe PTC patients who underwent thyroidectomy at the Thyroid Surgery Department of the Affiliated Hospital of Guizhou Medical University from March 2017 to May 2019 were retrospectively collected. Immunohistochemical staining was used to detect the expression of PD-L1 in the PTC tissues, PD-L1 staining positive cells ≥20% was judged as positive expression, <20% was judged as negative expression. The relationship between PD-L1 positive expression rate and clinicopathologic characteristics of patients with PTC were analyzed, and the correlation between the presence of HT in PTC tissues and PD-L1 positive expression was studied.ResultsA total of 138 patients with PTC were included in this study, including 104 patients with PTC alone and 34 PTC patients with coexistent HT. The positive rate of PD-L1 expression in the 138 cases of PTC tissues was 35.5% (49/138), among which was 43.3% (45/104) in the pure PTC tissues, and 11.8% (4/34) in the PTC tissues with HT, the latter was significantly lower than the former (P=0.001). The results of univariate analysis showed that the positive rate of PD-L1 expression was related to the tumor size, the presence or absence of extraglandular invasion and HT in PTC patients (P<0.05), and the results of Spearman correlation analysis showed that the positive rate of PD-L1 expression was positively correlated with tumor size (rs=0.173, P=0.041) and extraglandular invasion (rs=0.197, P=0.021), and negatively correlated with whether TH was merged (rs=–0.284, P=0.001). The multivariate analysis results showed that the positive rate of PD-L1 expression was closely related to whether PTC with coexistent HT [OR=5.720, 95%CI (1.879, 17.411), P=0.002], and it was not found to be related to tumor size and presence of extraglandular invasion (P>0.05).ConclusionsPositive rate of PD-L1 expression has a certain relationship with tumor size and presence or absence of extraglandular invasion, and which in PTC patients with or without HT is significantly different, that is, positive rate of PD-L1 expression in PTC with HT is lower suggests that coexistent HT might be an inhibitory factor in occurrence of PTC, and immune microenvironment-related factors of PTC might be involved in occurrence and development of thyroid cancer.
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.
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.
