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...
Accumulating evidence has indicated that microRNAs (miRNAs) play an important role in the occurrence and progression of ovarian cancer (OC). However, the function of miRNAs implicated in OC remains unclear. This study investigated the potential role of miR-211 in OC. Gene Expression Omnibus database analysis indicated that miR-211 expression was significantly down-regulated in OC tissues compared with normal specimens. In addition, miR-211 overexpression apparently inhibited proliferation, migration, xenograft growth, and induced apoptosis in HEY-T30 and SKOV3 cells. Moreover, PHF19, a component of the polycomb group of proteins, was found to be a direct target of miR-211 based on the luciferase reporter assay and Western blot analysis. Consistently, survival analysis indicated that high PHF19 expression was associated with shorter survival time in patients with OC. Importantly, silence of PHF19 reduced proliferation, induced cell cycle arrest, promoted apoptosis, suppressed migration, and inhibited xenograft growth in SKOV3 cells. Restoration of PHF19 expression markedly reversed the inhibitory effect of miR-211 on OC. Moreover, our results indicate that the long noncoding RNA MALAT1 could sponge miR-211 as a competing endogenous RNA and potentially up-regulate PHF19 expression, thus facilitating the OC progression. These findings suggest that the MALAT1/miR-211/PHF19 axis may act as a key mediator in OC and provide new insight into the prevention of this disease.-Tao, F., Tian, X., Ruan, S., Shen, M., Zhang, Z. miR-211 sponges lncRNA MALAT1 to suppress tumor growth and progression through inhibiting PHF19 in ovarian carcinoma.
The identification of safe and effective drugs that inhibit tumor invasion and metastasis is required to improve the clinical outcome of patients with colon cancer. The present study aimed to investigate the inhibitory effects and possible mechanisms of action of resveratrol against the invasion and metastasis of colon cancer. AKT1-knockdown SW480 and SW620 colon cancer cells were used to detect the effects of resveratrol on cell invasion and metastasis, as well as changes in the expression of epithelial-mesenchymal transition (EMT) markers and serine/threonine kinase (AKT)/glycogen synthase kinase (GSK)-3β/Snail signaling pathway-related molecules in vitro . Furthermore, nude mice were inoculated with SW480 cells in the tail vein to establish an in vivo lung metastasis model of colon cancer, to investigate the effects of resveratrol on lung metastasis in colon cancer. The results revealed that resveratrol treatment and AKT1 knockdown significantly inhibited cell migration and invasion in colon cancer, and markedly increased E-cadherin expression and decreased that of N-cadherin, phospho (p)-AKT1, p-GSK-3β, and Snail in colon cancer both in vitro and in vivo . Furthermore, the effects of resveratrol were significantly weaker in the AKT1-knockdown cells. In conclusion, resveratrol may suppress the invasion and metastasis of colon cancer through reversal of EMT via the AKT/GSK-3β/Snail signaling pathway. AKT1 may therefore be a key regulator of EMT in colon cancer cells and a potential therapeutic target for this disease.
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.
Background Lymph nodes metastasis (LNM) and distant metastasis (DM) are important prognostic factors in colorectal cancer (CRC) and determine the following treatment approaches. We aimed to find clinicopathological factors associated with LNM and DM, and analyze the prognosis of CRC patients with T1 stage. Methods A total of 17 516 eligible patients with T1 CRC were retrospectively enrolled in the study based on the Surveillance, Epidemiology, and End Results (SEER) database during 2004‐2016. Logistic regression analysis was performed to identify risk factors for LNM and DM. Unadjusted and adjusted Cox proportional hazard models were used to identify prognostic factors for overall survival. We performed the cumulative incidence function (CIF) to further determine the prognostic role of LNM and DM in colorectal cancer‐specific death (CCSD). LNM, DM, and OS nomogram were constructed based on these models and evaluated by the C‐index and calibration plots for discrimination and accuracy, respectively. The clinical utility of the nomograms was measured by decision curve analyses (DCAs) and subgroups with different risk scores. Results Tumor grade, mucinous adenocarcinoma, and age accounted for the first three largest proportion among the LNM nomogram scores (all, P < .001), whereas N stage, carcinoembryonic antigen (CEA), and tumor size occupied the largest percentage in DM nomogram (all, P < .001). OS nomogram was formulated to visually to predict 3‐, 5‐, and 10‐ year overall survivals for patients with T1 CRC. The calibration curves showed an effectively predictive accuracy of prediction nomograms, of which the C‐index were 0.666, 0.874, and 0.760 for good discrimination, respectively. DCAs and risk subgroups revealed the clinical effectiveness of these nomograms. Conclusions Novel population‐based nomograms for T1 CRC patients could objectively and accurately predict the risk of LNM and DM, as well as OS for different stages. These predictive tools may help clinicians to make individual clinical decisions, before clinical management.
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