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.
ObjectiveTo summarize research progress on programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors and their combination therapies in colorectal cancer and to provide a new treatment direction for colorectal cancer.MethodThe relevant literatures on the application of the PD-1/PD-L1 inhibitors in the colorectal cancer in recent years were collected and reviewed.ResultsThe clinical trials of anti-PD-1/PD-L1 signaling pathway antibodies had made some achievements in the colorectal cancer, especially in the patients with high frequency microsatellite instability. And the combination therapy of multiple antibodies and the combination with chemotherapy and targeted therapies were more effective.ConclusionPD-1/PD-L1 inhibitors have some certain curative effects on survival of colorectal cancer with high frequency microsatellite instability, especially combination shows a better effect.
Objective To explore the concept, contents and existing problems of the fast-track programmes in colorectal surgery. Methods The literatures about the applied status and opinion of the modality applied in the surgical treatment of the colorectal cancer and fundament investigation in recent years were collected and reviewed. Results The fast-track programmes enhance recovery of the patients who underwent the colorectal resection with the combination of multimodal techniques and approaches. Conclusion The fast-track programmes in colorectal surgery is the typical modality of the multi-disciplinary treatment, this modality can decrease the complications and reduce the hospital stay with preserve the well physiological fundament of the patients.
Objective To analyze the value of serum microRNAs (miR-218, miR-329, and miR-567) in predicting the clinical efficacy of programmed death-1 (PD-1) inhibitor combined with synchronous chemotherapy in patients with non-small cell lung cancer (NSCLC). Methods A total of 160 patients with NSCLC treated with PD-1 inhibitor combined with synchronous chemotherapy in Taiyuan Hospital, Peking University First Hospital between January 2021 and January 2023 were prospectively selected as the study objects by convenience sampling, and the serum levels of miR-218, miR-329, and miR-567 and the clinical efficacy of the patients were collected. According to the clinical efficacy, the patients were divided into remission group (partial remission and complete remission) and non-remission group (stable disease and disease progression). Receiver operating characteristic (ROC) curve was used to analyze the predictive value of serum miR-218, miR-329 and miR-567 levels in the clinical efficacy of PD-1 inhibitor combined with synchronous chemotherapy in patients with NSCLC. Results Of the 160 patients, 34 (21.2%) had disease progression, 85 (53.1%) had stable disease, 39 (24.4%) had partial remission, and 2 (1.2%) had complete remission. They were divided into remission group (41 cases) and non-remission group (119 cases). Multiple logistic regression analysis showed that high levels of serum miR-218, miR-329, and miR-567 could promote the clinical efficacy of PD-1 inhibitor combined with synchronous chemotherapy in patients with NSCLC (all P<0.05). ROC curve analysis showed that, for predicting the clinical efficacy of PD-1 inhibitor combined with synchronous chemotherapy in patients with NSCLC according to the cut-off value of the joint prediction probability of serum miR-218, miR-329, and miR-567, the area under the ROC curve was 0.938 [95% confidence interval (0.855, 0.964)], and the sensitivity, specificity, positive predictive value, and negative predictive value were 82.9%, 92.4%, 79.1%, and 94.0%, respectively. Conclusion The combined detection of serum miR-218, miR-329 and miR-567 levels has a high predictive value for the therapeutic effect of PD-1 inhibitor combined with synchronous chemotherapy in patients with NSCLC.
Age-related macular degeneration (AMD) involves dysregulation of the innate immune response of complement and mononuclear phagocytes and abnormalities of local microglia. When microglia transition from a resting state to an active state, their metabolic pathway also changes, known as "metabolic reprogramming", and their glucose metabolic reprogramming is a key factor in the pathogenesis of AMD, involving multiple signaling pathways. Including phosphatidylinositol 3-kinase-serine threonine kinase-rapamycin target, adenylate activated protein kinase and hypoxia-inducing factor 1 pathway. These metabolic changes regulate the inflammatory response, energy supply, and neuroprotective functions of microglia. Therapeutic strategies to regulate the reprogramming of glucose metabolism in microglia have achieved initial results. Future studies should further explore the mechanisms of microglia metabolic regulation to develop new targeted drugs and intervene in the treatment of AMD through anti-cellular aging pathways.
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.
There is a bidirectional association between tumor-associated macrophage (TAM) and colorectal cancer. Small molecular substances metabolized by colorectal cancer affect the reprogramming of TAM, and TAM in turn regulates the biological behavior of colorectal cancer cells by secreting small molecular substances, and promotes the progression of colorectal cancer. In addition, gut microbiota metabolites are closely related to TAM reprogramming, and intestinal flora imbalance leads to gut barrier damage, favoring bacterial translocation and causing chronic tumorigenic inflammation. Studying the reprogramming mechanism affecting TAM and its relationship with the occurrence and development of colorectal cancer may provide new ideas for the study of immunotherapy in patients with colorectal cancer. This article reviews the research progress of TAM in patients with colorectal cancer, aims to provide a reference for clinical research.
With the range of application of computational biology and systems biology gradually expanding, the complexity of the bioprocess models is also increased. To address this difficult problem, it is required to introduce positive alternative analysis method to cope with it. Taking the dynamic model of the epidemic control process as research object, we established an evaluation model in our laboratory. Firstly, the model was solved with nonlinear programming method. The results were shown to be good. Based on biochemical systems theory, the ODE dynamic model was transformed into S-system. The eigen values of the model showed that the system was stable and contained oscillation phenomenon. Next the sensitivities of rate constant and logarithmic gains of the three key parameters were analyzed, as well as the robust of the system. The result indicated that the biochemical systems theory could be applied in different fields more widely.
Macrophages are important immune effector cells with significant plasticity and heterogeneity in the body immune system, and play an important role in normal physiological conditions and in the process of inflammation. It has been found that macrophage polarization involves a variety of cytokines and is a key link in immune regulation. Targeting macrophages by nanoparticles has a certain impact on the occurrence and development of a variety of diseases. Due to its characteristics, iron oxide nanoparticles have been used as the medium and carrier for cancer diagnosis and treatment, making full use of the special microenvironment of tumors to actively or passively aggregate drugs in tumor tissues, which has a good application prospect. However, the specific regulatory mechanism of reprogramming macrophages using iron oxide nanoparticles remains to be further explored. In this paper, the classification, polarization effect and metabolic mechanism of macrophages were firstly described. Secondly, the application of iron oxide nanoparticles and the induction of macrophage reprogramming were reviewed. Finally, the research prospect and difficulties and challenges of iron oxide nanoparticles were discussed to provide basic data and theoretical support for further research on the mechanism of the polarization effect of nanoparticles on macrophages.
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.