Anti-PD-1/PD-L1 inhibitors provide a survival advantage over conventional therapies for treatment of advanced or metastatic cancer. However, the factors determining which patients benefit the most from anti-PD-1/PD-L1 inhibitors are unknown, making treatment-related decisions difficult. We performed a systematic review and meta-analysis of acquired data to assess the efficacy and toxicity of anti-PD-1/ PD-L1 inhibitors in advanced and metastatic cancer. A thorough search strategy was applied to identify randomised controlled trials (RCTs) in Pubmed, Embase, Cochrane, and major conferences. Studies meeting predefined selection criteria were selected, and two independent investigators performed data extraction; overall survival (OS), progression-free survival (PFS), and overall response rate were compared between anti-PD-1/PD-L1 inhibitors and control therapies. We calculated the pooled response rate and 95% CIs of all-grade and high-grade (≥3) adverse effects and evaluated the withinstudy heterogeneity using subgroup, sensitivity, and meta-regression analyses. In final, we included eligible 35 RCTs (21047 patients). The main estimated hazard ratios (HRs) for OS and PFS were 0.76 (0.71-0.82) and 0.81 (0.73-0.89) in a random-effects model. The anti-PD-1/PD-L1 inhibitor group had a significantly high risk for all-grade immune-related adverse events. Anti-PD-1/PD-L1 inhibitors were identified as a preferable treatment option for advanced or metastatic cancer patients who are male, aged < 65 years, current or former smokers, had no CNS or liver metastasis, had not EGFR mutation, and had high PD-L1 expression.Cancer is a common cause of death, accounting for more than 9.56 million deaths annually 1 . Over half of cancer patients have a poor prognosis due to locally advanced or systemic metastasis. For the majority of these cases, treatment with conventional therapies, such as chemotherapy and radiotherapy, does not improve their prognosis. Recently, several immune checkpoint inhibitors (ICIs), have been developed and approved for a wide range of tumour types and having shown potential for maintaining homeostasis and eliminating tumour cells. Immunotherapies targeting immune checkpoint pathways have shown potential for generating a durable response and for prolonging disease stabilisation in a significant proportion of inoperable, advanced, or recurrent cancers in patients with multiple cancer types, along with favourable tolerability. In addition to their use as a monotherapy, the general safety of immune checkpoint agents also allows for their use in the development of combined therapies for cancer treatment; combining ICIs with other conventional treatments or targeted therapies is expected to improve anti-tumour activity and increase ICI efficacy. However, although durable responses were reported in cancer patients treated with combination strategies involving ICIs, it is still necessary to optimise dose selection to minimise the adverse events (AEs) caused by combination regimens while maintaining stable clinical ef...

The outbreak caused by COVID-19 is causing a major challenge to clinical management and a worldwide threat to public health. So far, there is no specific anti-coronavirus therapy approved for the treatment of COVID-19. Recently, as the efficacy and safety of traditional Chinese medicine (TCM) is widely acknowledged, it has been brought to a crucial status by the public, governments, and World Health Organization (WHO). For a better popularization of TCM, governments have made several advances in regulations and policies for treatment and measures of novel coronavirus pneumonia (NCP). Therefore, on the basis of epidemiology and virology information, we reviewed relevant meta-analysis and clinical studies of anti-coronavirus therapeutics by TCM, in the aspect of mortality, symptom improvement, duration and dosage of corticosteroid, incidence of complications and the like. In addition, we also summarized preclinical rationale for anti-coronavirus activity by TCM in terms of virion assembly and release, as well as viral entry and replication, which could be a useful contribution for figuring out effective Chinese herbal medicine (CHM) for coronavirus, including ingredients from single monomeric compounds, Chinese herbs, Chinese herb extracts and Chinese herb formulas, or potential targets for medicine. We would like to see these relevant studies, ranging from basic researches to clinical application, could provide some idea on effects of CHM to combat COVID-19 or other coronaviruses, and also offer new thinking for the exploration of therapeutic strategies under the guidance of TCM.

Objectives. Despite the fact that it is widely acknowledged that immune checkpoint inhibitors (ICIs) rely on the presence of immune response to take their antitumor effect, little is known whether there is an influence exerted on the efficacy of ICIs based on patients’ age. We performed a systematic review and meta-analysis to explore the efficacy of ICIs between younger and older patients. Materials and Methods. We searched online database and major conference proceedings for randomized controlled trials (RCTs) published of ICIs and included RCTs that conducted subgroup comparisons of age with available combination of hazard ratios (HRs) and 95% confidence interval (95%CI). Subsequently, we figured out the pooled HR and 95%CI in younger and older patients with a random-effects model and evaluated the within-study heterogeneity by using subgroup, sensitivity, and meta-regression analysis. Results and Conclusion. A total of 12 eligible RCTs included in our study, which reported OS according to patients’ age. The overall estimated random-effects for HR was 0.75 with 95% CI of 0.65-0.87 in younger arm versus 0.81 with 95% CI of 0.72-0.92 in older arm. ICIs can improve OS for patients with advanced or metastatic lung cancer when compared to controls, especially for those patients with NSCLC, anti-PD-1/PD-L1 inhibitors, non-squamous, Pembrolizumab or Atezolizumab used as well as subsequent-line setting, and the magnitude of benefit in OS had comparable efficacy in both younger and older arms using a cut-off of 65 yr. Conversely, we also drew a statically significant conclusion that older patients failed to acquire benefit from ICIs when subdivided with a further cut-off of 75 yr.

Background: Jiedu Sangen Decoction (JSD), a traditional Chinese medicine formula, has been widely applied in the treatment of gastrointestinal cancer, especially in colorectal cancer. Our study mainly aimed to assess the combined efficacy of Jiedu Sangen aqueous extract (JSAE) and a PD-L1 inhibitor (PI) in colon cancer cells migration and invasion, along with epithelial-mesenchymal transition, and then provide deep insights into the potential mechanism. Methods: We explored the inhibitory effects on invasion and metastasis and the reverse effect on EMT process in CT-26 colon cancer cell via Transwell migration assay, Matrigel invasion assay and confocal laser scanning microscopy. Furthermore, regulation in expression of EMT-related proteins and molecular biomarkers and underlying signal pathway proteins were detected through Western blotting and IHC. Results: The combination of JSD and PD-L1 inhibitor could inhibit migration, invasive ability and EMT of CT-26 cells in a concentration-dependent manner. Meanwhile, JSD combined with PD-L1 inhibitor could also remarkably reverse EMT and metastasis in vivo. In addition, the protein expression of N-cadherin, Slug, Snail, Vimentin was down-regulated along with E-cadherin s up-regulation with the combination of JSD and PD-L1 inhibitor, while that of PI3K/AKT was notably down-regulated. Conclusions: These findings indicated that JSAE and a PD-L1 inhibitor could drastically inhibit the migration and invasion of colorectal cancer by reversing EMT through the PI3K/AKT signaling pathway.

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BackgroundCancer, with sustained high mortality, is a worldwide threat to public health. Despite the survival benefit over conventional therapies shown in immune checkpoint inhibitor (ICI), only a minority of patients benefit from single ICI. But combination therapy holds the promise of achieving better efficacy over monotherapy. We performed a systematic review and meta-analysis to assess the efficacy and safety of ICI-based combination therapy for cancer.MethodsA search was conducted to retrieve relevant studies in electronic databases and major conferences. Two investigators independently performed data extraction, making a systematic data extraction, assembly, analysis and interpretation to compare the overall survival (OS), progression-free survival (PFS), overall response rate (ORR), all and high grade immune related adverse events (IRAEs) between combination therapy and monotherapy. Therefore, only the studies satisfying the criteria were included. Finally, we performed subgroup, sensitivity, and publication bias analysis to examine the heterogeneity and bias of resources.ResultsA total of 2,532 patients from thirteen studies were enrolled. Compared to ICI alone, combination therapy, with a high risk and high grade IRAEs for the majority of all, offers a better survival benefit (OS: HR: 0.86, 95% CI: 0.76 to 0.98; PFS: HR: 0.79, 95% CI: 0.69 to 0.90) and objective response (ORR: RR: 1.91, 95% CI: 1.40 to 2.60).ConclusionsICI-based combination therapy was confirmed as the optimum treatment for cancer, especially when using specific dosage and regimen to treat certain tumor types with no absolute demand for the detection of PD-L1 expression. Meanwhile, attention should also be paid on potential toxicity, especially the IRAEs.

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Jiedu Sangen Decoction (JSD), a traditional Chinese medicine (TCM) formula, has been widely used in China to treat gastrointestinal cancer, especially as an adjuvant therapy in colorectal cancer (CRC) patients. This study aimed to evaluate the efficacy of JSD and Jiedu Sangen aqueous extract (JSAE) in colon cancer cells and explored the underlining mechanisms by cytotoxicity assay, scratch assay, transwell migration assay, matrigel invasion assay, confocal laser scanning microscopy, and western blot analysis. We demonstrated that JSAE inhibited the growth of colon cancer SW480 cells in a dose-dependent manner and JSAE repressed cancer cell migration and invasion. Furthermore, epithelial mesenchymal transition (EMT) was reversed by JSAE via enhancing E-cadherin expression and attenuating protein levels of EMT promoting factors such as N-cadherin, Slug, and ZEB1. These findings provided the first experimental evidence confirming the efficacy of JSAE in repressing invasion and metastasis of CRC and paving a way for the broader use of JSD in clinic.