Objective To investigate the role of ephrin A genes in the development of oxygen induced retinalneovascularization (OIR) in mice.Methods The OIR model was established by oxygen induction in new born C57BL/6J mice.Reversed transcript polymerase chain reaction (RT-PCR) was used to measure the expression levels of ephrin A1-A5 in retinas of mice in experimental and normal control group.Results All of the ephrin A family genes expressed in normal retinas. Ephrin A1 mRNA was significantly higher in OIR group(t=3.19,P=0.019); ephrin A2 mRNA was higher in the 15-day-old OIR retinas(t=3.71,P=0.033）; ephrin A3-A5 mRNA decreased or disappeared in 12 and 13-day-old RNV mice, and increased in 15-day-old OIR mice. Conclusion Ephrin A genes are involved in the development of retina and OIR.
Objective To study the expressions of human ether-a-go-go related gene (HERG) in CD1 mice gallbladder and interstitial cells of Cajal (ICC) and explore their possible implications. Methods The expression of HERG protein in gallbladder tissue slices obtained from CD1 mice was detected by immunohistochemistry method. The expression of HERG mRNA in gallbladder tissue was detected by reverse transcription (RT)-PCR. The production of HERG protein was confirmed in the CD1 mice gallbladder by Western blot. Enzymatically dispersed cells were identified as ICC using the specific ICC marker c-kit antibody, and the double positive cells of c-kit and HERG were observed by laser passing confocal microscope. Results HERG was present in the CD1 mice gallbladder tissues for the yellow or buffy positive reaction. At the same time, the expression of mRNA specific for the HERG gene and production of HERG protein in the CD1 mice gallbladder tissues were indicated by RT-PCR and Western blot analysis, respectively. Using double labeling of anti-c-kit and anti-HERG, the double positive cells of c-kit and HERG were observed in the CD1 mice ICC by laser passing confocal microscope. Conclusion The study demonstrates that HERG is present in the CD1 mice gallbladder tissues and ICC, which is likely related to the pacemaking activity of ICC.
Objective To systematically review the efficacy and safety of tyrosine kinase inhibitors combined with chemotherapy versus chemotherapy in advanced non-small cell lung cancer(NSCLC). Methods An electronically search was conducted in The Cochrane Library, PubMed and EMbase databases from inception to December 2016 to collect randomized controlled trials (RCTs) about tyrosine kinase inhibitors combined with chemotherapy versus chemotherapy for NSCLC. 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. Results A total of 12 RCTs involving 6 559 patients were finally included. The results of meta-analysis showed that: The median progression free survival (PFS) (HR=0.86, 95%CI 0.81 to 0.91, P<0.001) and objective response rate (ORR) (HR=1.43, 95%CI 1.20 to 1.70,P<0.001) of tyrosine kinase inhibitors combined with chemotherapy were significantly longer than those of the chemotherapy group. There were no significant differences between two groups in incidence of median overrall survival (OS) (HR=0.91, 95%CI 0.82 to 1.00,P=0.06), fatigue (RR=1.03, 95%CI 0.97 to 1.11, P=0.33), dyspnea (RR=1.01, 95%CI 0.91 to 1.13, P=0.82) and cough (RR=1.01, 95%CI 0.89 to 1.15, P=0.91). However, the incidence of neutrocytopenia (RR=1.16, 95%CI 1.05 to 1.28, P=0.003), thrombocytopenia (RR=1.46, 95%CI 1.23 to 1.73, P<0.001), diarrhea and hypertension (RR=2.91, 95%CI 2.28 to 3.71,P<0.001) of tyrosine kinase inhibitors combined with chemotherapy group were significantly higher than those of the chemotherapy group. The tyrosine kinase inhibitors combined with chemotherapy group had lower rate of anemia (RR=0.86, 95%CI 0.75 to 0.98,P=0.03). Conclusion Compared with chemotherapy alone, tyrosine kinase inhibitors combined with chemotherapy can improve the median PFS and ORR while it can be used as a treatment for advanced non-small cell lung cancer patients. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify above conclusion.
ObjectivesTo systematically review the risk of arterial ischemic and metabolic adverse events in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs).MethodsPubMed, EMbase, The Cochrane Library, CNKI, WanFang Data and VIP databases were searched to collect clinical trials, observational studies and case reports of adverse events in CML patients treated with TKIs from inception to February 2017. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then, meta-analysis was performed by using Stata 12.0 software.ResultsA total of 22 studies involving 4 223 patients were included. The incidence rates of ischemic heart disease in any grade were 2 per 100 patient-years (95%CI 2 to 3) for nilotinib, and 0 per 100 patient-years (95%CI 0 to 3) for imatinib. The incidence of ischemic heart disease in grade 3 or 4 was 1 per 100 patient-years (95%CI 0 to 2) for nilotinib. The incidence of peripheral arterial occlusive disease in any grade was 2 per 100 patient-years (95%CI 0 to 14) for nilotinib, and 0 per 100 patient-years (95%CI 0 to 2) for imatinib. The incidence of hypertension in any grade was 1 per 100 patient-years (95%CI 0 to 3) for nilotinib, and 44 per 100 patient-years (95%CI 27 to 71) for ponatinib. The incidence of hypertension in grade 3 or 4 was 2 per 100 patient-years (95%CI 0 to 15) for nilotinib, and 22 per 100 patient-years (95%CI 8 to 58) for ponatinib. The incidence of hyperlipidemia in any grade was 17 per 100 patient-years (95%CI 5 to 59) for nilotinib. The incidence of hyperglycemia in any grade was 11 per 100 patient-years (95%CI 9 to 15) for nilotinib, 2 per 100 patient-years (95%CI 1 to 4) for imatinib, 1 per 100 patient-years (95%CI 0 to 5) for dasatinib, and 19 per 100 patient-years (95%CI 19 to 20) for bosutinib. The incidence of hyperglycemia in grade 3 or 4 was 4 per 100 patient-years (95%CI 3 to 5) for nilotinib, and 1 per 100 patient-years (95%CI 1 to 2) for bosutinib.ConclusionsPatients treated with nilotinib have a greater possibility of ischemic heart and peripheral arterial occlusive disease compared with patients treated with imatinib. Patients treated with ponatinib have a high incidence rate of hypertension, and patients treated with nilotinib have a high incidence rate of hyperlipidemia. Patients treated with bosutinib and nilotinib have higher risk of hyperglycemia compared with patients treated with imatinib or dasatinib.
ObjectiveTo systematically review the efficacy and safety of different tyrosine kinase inhibitors (TKIs) in the treatment of chronic myelocytic leukemia (CML).MethodsPubMed, EMbase, The Cochrane Library, CBM, WanFang Data and CNKI databases were electronically searched to collect randomized controlled trials (RCTs) of nilotinib, dasatinib, flumatinib and imatinib for CML from inception to August, 2020. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies; network meta-analysis was then performed using Stata 15.0 software and R 3.4.0 software.ResultsA total of 8 RCTs involving 2 775 patients were included. Compared with other TKIs, flumatinib had higher 3-month early molecular response and 1-year progression free survival, and the incidence of serious side effects was relatively low. Major molecular response and complete cytogenetic response were significantly superior to imatinib, and had the same or similar effects to other second-generation TKIs.ConclusionsCurrent evidence shows that flumartinib in the treatment of CML is obviously superior to imatinib, has the same or similar effect with other second generation TKIs. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify above conclusions.
ObjectiveTo systematically review the renal adverse reactions of tyrosine kinase inhibitors (TKI). MethodsPubMed, EMbase, Cochrane Library, CNKI, WanFang Data and CBM databases were electronically searched to collect randomized controlled trials (RCTs) on the incidence of renal adverse reactions of TKI from inception to March 30, 2023. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed by using RevMan 5.4 software. ResultsA total of 19 RCTs involving 10 141 patients were included. The results of meta-analysis showed that compared with placebo or blank control, gefitinib, ranvartinib, cabotinib, vandetanib, pazopanib, arotinib, apatinib, and acitinib could lead to an increased risk of proteinuria events, while sildenib did not increase the risk of proteinuria in patients. Anlotinib could increase the risk of hematuria. Vandetanil increased the risk of acute kidney injury. Gefitinib, ranvartinib and apatinib could increase the risk of grade 3-4 renal adverse reactions. ConclusionCurrent evidence shows that TKI drugs may cause renal damage in patients, and proteinuria is the most common. Vandetanil can cause acute kidney injury, gefitinib, ranvartinib and apatinib are more nephrotoxic. The renal adverse reactions of neratinib, ibutinib and sildenib are relatively few.
ObjectiveTo explore the protective effect and mechanism of Krüppel-like factor 7 (KLF7) overexpression on retinal ganglion cells (RGC) in mice after optic nerve crush (ONC). MethodsA total of sixty five 10-week-old C57BL/6J mice were randomly divided into five groups: blank control group (group A), intravitreal injection (IVT)-KLF7 group (group B), IVT-phosphate buffer saline-ONC group (group C), IVT-KLF7-ONC group (group D), and IVT-recombinant adeno-associated virus 2-enhanced green fluorescent protein-ONC group (group E), with 13 mice in each group. On the 7 days after the ONC model, the mice in each group were killed. RGC survival rate was counted by whole retina flat mount and immunofluorescence techniques. KLF7, nerve growth factor (NGF), tyrosine kinase A (TrkA), phosphorylated TrkA (pTrkA), tyrosine kinase B (TrkB) and phosphorylated TrkB (pTrk) were detected by western blot, growth associated protein 43 (GAP43), brain-derived neurotrophic factor, B lymphoblastoma-2 (Bcl-2), Bcl-2 associated X protein (BAX), Caspase-3 protein relative expression levels. One-way analysis of variance or Kruskal-Wallis test were used for comparison between groups. ResultsOn the 7 days after the ONC model, the density of RGC in the retina of groups A, B, C, D and E were (3 707.4±12.8), (3 582.4±13.3), (1 396.3±16.1), (1 658.3±22.2) and (1 323.6±16.9)/mm2, respectively. Compared with groups C and E, RGC density in group D was significantly increased, and the difference was statistically significant (P=0.028, 0.007). Compared with groups A, B, C and E, the relative expression levels of NGF, pTrkA, pTrkB, GAP43 and Bcl-2 proteins in the retina of mice in group D were increased, while the relative expression levels of BAX and Caspase-3 proteins were decreased, with statistical significance (P＜0.01). ConclusionIn mouse ONC model, overexpression of KLF7 can improve RGC survival rate, increase the relative expression levels of NGF, pTrkA, pTrkB, GAP43 and Bcl-2 proteins in retina, and decrease the relative expression levels of BAX and Caspase-3 proteins.