ObjectiveTo detect FoxM1 expression in thyroid papillary carcinoma TPC-1 cells,and explore influence of FoxM1 expression on important genes (RAS gene and CDK1 gene) of mitogen activated protein kinase (MAPK) signal pathway. MethodsThe hFoxM1-RNA interference was used to deal with the thyroid papillary carcinoma TPC-1 cells (experiment group),another untreated TPC-1 cell was as control group.Then the real-time quantitative PCR was used to detect the FoxM1,Ras,and CDK1 gene expressions in all the TPC-1 cells. ResultCompared with the control group,the FoxM1 gene expression was significantly decreased (0.452 9 versus 1.005 0,t=24.692 9,P<0.01),the Ras gene expression was significantly elevated (1.319 0 versus 1.001 2,t=14.218 5,P<0.01),and the CDK1 gene expression was significantly decreased (0.767 5 versus 1.008 1，t=10.763 4,P<0.01) in the experiment group. ConclusionFoxM1 gene expression level in thyroid papillary carcinoma TPC-1 cells could influence Ras and CDK1 expression,which suggests that its role in thyroid papillary carcinoma might be associated with MAPK signal pathway.
Objective To study relation between expression of cyclin-dependent kinase like 5 (CDKL5) in gastric cancer tissue and clinicopathologic characteristics of patients with gastric cancer. Methods The expressions of CDKL5 mRNA and protein in 45 gastric cancer tissues and their corresponding adjacent tissues were detected by real-time quantitative PCR and Western blot methods respectively. Meanwhile the expressions of CDKL5 protein in gastric cancer cell lines including AGS and MKN-45 were detected by immunofluorescence method. Results The CDKL5 mRNA and protein highly expressed in the 45 primary gastric cancer tissues as compared with the their corresponding adjacent tissues (P<0.05). The results of univariate analysis identified that the age (P=0.033), vascular invasion (P=0.007), T stage (P=0.049), and TNM stage (P=0.041) were associated with the expression of CDKL5 mRNA in the primary gastric cancer tissues. The results of multivariate regression analysis showed that the vascular invasion (P=0.013) and TNM stage (P=0.024) were the important factors affecting the expression of CDKL5 in the primary gastric cancer tissues. The CDKL5 protein expressions were found at fragments with relative molecular masses of 107×103 and 85×103 in the primary gastric cancer tissues and gastric cancer cell lines. Conclusions CDKL5 mRNA and protein highly express in primary gastric cancer tissue and relate to vascular invasion and TNM stage. The CDKL5 protein expresses at fragments with relative molecular masses of 107×103 and 85×103 in primary gastric cancer tissues and gastric cancer cell lines suggest that CDKL5 has different expressing way in protein level.
ObjectiveTo systematically review the efficacy and safety of CDK4/6 inhibitors combined with endocrine therapy for advanced breast cancer.MethodsPubMed, EMBase, The Cochrane Library, CNKI, WanFang Data and VIP databases were electronically searched to collect randomized controlled trials (RCTs) of CDK4/6 inhibitors combined with endocrine therapy for advanced breast cancer from inception to October 13th, 2017. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then, meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 4 RCTs involving 2 524 patients were included. The results of meta-analysis showed that: compared with placebo combined with endocrine therapy, CDK4/6 inhibitors combined with endocrine therapy could improve the median progression free survival rate (RR=0.53, 95%CI 0.47 to 0.60, P<0.000 01) and the objective response rate (RR=1.67, 95%CI 1.47 to 1.91,P<0.000 01). While there was no statistical difference in clinical benefit rate (RR=0.59, 95%CI 0.75 to 1.19,P=0.64). In terms of adverse reactions, CDK4/6 inhibitors combined with endocrine therapy had higher rates of neutropenia (RR=49.76, 95%CI 26.85 to 90.21, P<0.000 01), leukopenia (RR=48.69, 95%CI 18.74 to 133.61,P<0.000 01), fatigue (RR=3.11, 95%CI 1.37 to 7.08,P=0.007) and anemia (RR=2.96, 95%CI 1.61 to 5.42, P=0.000 3). There were no significant differences between two groups in nausea, diarrhea and decreased appetite.ConclusionCDK4/6 inhibitors combined with endocrine therapy for the patients with advanced breast cancer can improve median progression free survival and objective response rate, while increase the incidence of adverse events such as neutropenia, leukopenia, fatigue and anemia. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify above conclusion.
ObjectiveTo analyze the expression and clinical significance of cyclin-dependent kinase 1 (CDK1) in lung adenocarcinoma by bioinformatics.MethodsBased on the gene expression data of lung adenocarcinoma patients in The Cancer Genome Atlas (TCGA), the differential expression of CDK1 in lung adenocarcinoma tissues and normal lung tissues was analyzed. The expression of CDK1 gene in lung adenocarcinoma was analyzed by UALCAN at different angles. Survival analysis of different levels of CDK1 gene expression in lung adenocarcinoma was performed using Kaplan-Meier Plotter. Correlation Cox analysis of CDK1 expression and overall survival was based on clinical data of lung adenocarcinoma in TCGA. Gene set enrichment analysis was performed on gene sequences related to CDK1 expression in clinical cases. The protein interaction network of CDK1 from Homo sapiens was obtained by STRING. CDK1-related gene proteins were obtained and analyzed by the web server Gene Expression Profiling Interactive Analysis (GEPIA).ResultsBased on the analysis of TCGA gene expression data, CDK1 expression in lung adenocarcinoma was higher than that in normal lung tissues. UALCAN analysis showed that high CDK1 expression may be associated with smoking. Survival analysis indicated that when CDK1 gene was highly expressed, patients with lung adenocarcinoma had a poor prognosis. Univariate and multivariate Cox regression analysis of CDK1 expression and overall survival showed that high CDK1 expression was an independent risk factor for survival of patients with lung adenocarcinoma. Gene set enrichment analysis revealed that high CDK1 expression was closely related to DNA replication, cell cycle, cancer pathway and p53 signaling pathway.ConclusionCDK1 may be a potential molecular marker for prognosis of lung adenocarcinoma. In addition, CDK1 regulation may play an important role in DNA replication, cell cycle, cancer pathway and p53 signaling pathway in lung adenocarcinoma.
CDKL5 deficiency disorder (CDD), also known as developmental epileptic encephalopathy, is a rare X-linked dominant disease of the nervous system. Its main clinical manifestations include: uncontrollable seizures, cognitive impairment, motor retardation, visual impairment, sleep disorders, gastrointestinal impairment, autonomic nervous dysfunction, and autistic like manifestations. Its high disability rate and heavy disease burden bring heavy burden to society and family. However, the current domestic and foreign studies on this disease mainly focus on the clinical phenotype and pathogenesis, and there are few studies involving the standard clinical management of various systems. Therefore, a core committee composed of CDD experts from the United States, Europe, and the United Kingdom conducted a six-month investigation (August 2020—January 2021) and developed the international consensus: recommendations for the assessment and management of CDKL5 deficiency patients (hereafter referred to as the Consensus) based on the Durfel research methodology. This consensus invites multidisciplinary experts to put forward diagnosis and treatment suggestions for the diagnosis and treatment of CDD as well as the clinical management of various systemic systems, which will provide evidence-based basis for regulating the diagnosis and treatment behaviors of clinicians for CDD. In this paper, the consensus was interpreted to facilitate the long-term management of the disease.
Objective To compare the efficacy and safety of different cyclin-dependent kinase4/6 inhibitor (CDK4/6i) combined with endocrine therapy (ET) for HR+/HER2- advanced or metastatic breast cancer based on mesh meta-analysis. Methods Randomized controlled trials (RCTs) of CDK4/6i in the treatment of HR+/HER2- metastatic/advanced breast cancer were searched in PubMed, EMbase, Web of Science, The Cochrane Library, CNKI, Wanfang, VIP, and SinoMed databases from inception to August 2023. Bayesian network meta-analysis was performed by R 4.2.0 software. Results Finally, 18 RCTs in 25 articles, covering 8 031 patients, involving 11 treatment regimens were included. There were no statistical differences in progression-free survival (PFS) or overall survival (OS) between CDK4/6i+ET combinations. DAL+FUL ranked first in PFS rate, and RIB+FUL ranked first in OS rate. In terms of effectiveness, ABE+AI and ABE+FUL ranked first in objective response rate (ORR) and clinical benefit rate (CBR), respectively. In terms of safety, there were significant differences in grade 3-4 AEs and SAE among some CDK4/6i types (P<0.05). Conclusion Current evidence shows that CDK4/6i+ET is superior to ET alone in the treatment of HR+/HER2- advanced/metastatic breast cancer, and different combinations of CDK4/6i+ET have the same or similar effects, but the combination has a higher incidence of adverse reactions, and a reasonable treatment plan should be selected according to the individual situation of patients.
Objective To systematically review the efficacy and safety of CDK4/6 inhibitors in combination with endocrine therapy for HR+/HER2‒ breast cancer. Methods The PubMed, Cochrane Library, Web of Science, WanFang Data, CNKI, American Society of Clinical Oncology (ASCO), European Society of Medical Oncology (ESMO) and San Antonio Breast Cancer Symposium (SABCS) databases were electronically searched to collect randomized controlled trials on CDK4/6 inhibitors in combination with endocrine therapy for HR+/HER2‒ breast cancer from inception to July 5, 2023. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. Meta-analysis was then performed using RevMan 5.4 software and Stata 14.0 software. Results A total of 8 studies involving 4 580 patients were included. The results of meta-analysis showed that overall survival and progression-free survival were significantly longer in the combination therapy group than those in the endocrine therapy alone group (HR=0.80, 95%CI 0.73 to 0.89, P<0.05; HR=0.54, 95%CI 0.50 to 0.59, P<0.05). The results also showed that patients in the combination therapy group also had significantly higher rates of objective remission and clinical benefit than those in the endocrine therapy group alone (RR=1.47, 95%CI 1.34 to 1.62, P<0.05; RR=1.20, 95%CI 1.11 to 1.30, P<0.05). In addition, the combination treatment group also increased the incidence of haematological toxicity such as neutropenia and leucopenia, but the differences in the incidence of nausea, diarrhoea and headache were not statistically significant between the two groups. Conclusion The combination of CDK4/6 inhibitors with endocrine therapy for HR+/HER2‒ breast cancer patients improve overall survival, progression-free survival, clinical benefit rate and objective remission rate, with significant long-term and near-term efficacy; however, this regimen increased the incidence of several adverse effects, and clinical use should be considered when considering the occurrence of serious adverse effects.