Tyrosine kinase inhibitors (TKIs) are the standard of care for non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutation. The efficacy of TKIs and prognosis of EGFR-mutated patients with compound EGFR mutation, oncogene mutation, suppresser gene mutation or other diver gene mutation are worse than those of patients with a single EGFR mutation. This article makes a review of related clinical researches aiming to provide references for clinical scenarios. To sum up, molecular alterations and clinical features should be correlated as accurately and dynamically as possible in the diagnostic and therapeutic process, and combined therapeutic strategies should be chosen flexibly and reasonably to improve patients’ survival and prognosis.
Objective To summarize the traits of calcium-binding tyrosine phosphorylation regulate gene and the significance in tumor incidence. Methods The domestic and foreign literatures about calcium-binding tyrosine phosphorylation regulate gene involved in the regulation of signaling pathways and research status in a variety of tumors were reviewed. Results Calcium-binding tyrosine phosphorylation regulate gene induced the abnormal proliferation of cells through multiple mechanisms. There was closely relation between the occurrence of many tumors and abnormal expression of calcium-binding tyrosine phosphorylation regulate gene. In the distribution of different epithelial tumors， the pathway of calcium-binding tyrosine phosphorylation regulate gene involved in the regulation was same， and the effect target was similar. Conclusion Further study of the calcium-binding tyrosine phosphorylation regulate gene is expected to provide a new way for clarify the occurrence and development mechanisms of tumors， and can serve as important means of early diagnosis and adjuvant therapy.
ObjectiveTo expounded the relationship between phenylalanine, tyrosine and their metabolites and non-alcoholic fatty liver disease (NAFLD). MethodThe literatures related to NAFLD in recent years were reviewed and analyzed. ResultThe levels of phenylalanine, tyrosine and their metabolites had changed significantly in the occurrence and development of NAFLD, and could lead to the progress of NAFLD by affecting the related pathways of lipid metabolism. ConclusionPhenylalanine, tyrosine and their related metabolites are associated with NAFLD, but the specific pathogenesis is still unclear.
Objective To evaluate the effects of two different epidermal growth factor receptor tyrosine kinase inhibitors ( EGFR-TKIs) , Gefitinib and Erlotinib, on lung fibrosis induced by bleomycin.Methods Forty BALB/c female mice were randomly divided into four groups, ie. a control group( saline given orally and intratracheally) , a fibrosis group( saline given orally with bleomycin instillation) , a Gefitnib group( Gefitnib 20 mg/kg given orally with bleomycin instillation) , and an Erlotinib group ( Erlotinib25 mg/kg given orally with bleomycin instillation) . Bleomycin ( 3 mg/kg) was intratracheally instilled on the first day. Gefitinib or Erlotinib was given orally daily and normal saline as control. Then they were sacrificed by abdominal aortic bleeding 14 days after the bleomycin instillation. The left lung was stained with HE and Masson’s trichrome staining respectively for pathological examination. Total EGFR and phosphorylated EGFR were detected by immunohistochemistry. Hydroxyproline ( HYP) assay was performed in the right lung.Results Both Gefitinib and Erlotinib significantly reduced lung collagen accumulation and the content of HYP. Immunohistochemistry revealed that phosphorylation of EGFR in lung mesenchymal cells induced by bleomycin was inhibited. Furthermore, there was no difference between Gefitinib and Erlotinib in inhibiting lung fibrosis. Conclusion Our findings suggest that, in the preclinical setting, EGFR-TKIs may have aprotective effect on lung fibrosis induced by bleomycin.
Objective By using small interfering RNAs ( siRNAs) specific for spleen tyrosine kinase ( Syk) , to evaluate the role of Syk in maturation of bone marrow-derived dendritic cells. Methods The fragments of 21-23 bp siRNAs specific for mice Syk were chemo synthesized and transfected into the asthmatic murine bone marrow-derived dendritic cells ( BMDCs) by Lipofectamine 2000 transfection system for 48 hours. Then BMDCs were co-cultured with T cells from the normal mice spleen for 48 hours. The cytokines including IL-4, IL-13, IL-2 and INF-γin supernatant were detect by ELISA. The expression of Syk protein was measured by Western Blot to determine whether the Syk gene was silenced. Results The expression of Syk protein was obviously decreased in the siRNA-interference group. The secretions of IL-4 and IL-13 were significantly inhibited by siRNA interference ( P lt; 0. 05) , but the secretions of IL-2 and INF-γwere not interfered signficantly ( P gt;0. 05) . Conclusion Syk specific siRNA fragments can block the antigen presentation function of dendritic cells and block the activation and differentiation of T cells.
The resistance of non-small cell lung cancer (NSCLC) to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has been brought into focus. COX-2 signal pathway was found to be closely related to EGFR signal pathway by recent researches, and there has been a growing interest to focus the researches on whether COX-2 pathway inhibition improves the efficacy of EGFR-TKIs in treating advanced NSCLC. In this review, we will illustrate recent advances of combined inhibition of EGFR and COX-2 signal pathways in NSCLC therapy.
The incidence and mortality of esophageal cancer in China rank the fifth and fourth, respectively, with squamous carcinoma accounting for more than 90%. Currently, the treatment of esophageal squamous carcinoma mainly includes surgery, chemotherapy, radiotherapy, and endoscopic treatment. However, the 5-year survival rate is only about 20%. At present, the treatment of esophageal squamous carcinoma seems to reach a plateau. Thus, it is urgent to develop new and more effective drugs and treatments. In this paper, the clinical research progresses of epidermal growth factor receptor (EGFR)- targeted therapy of esophageal squamous carcinomas were summarized, including anti-EGFR monoclonal antibodies, such as cetuximab and nimotuzumab, and EGFR-tyrosine kinase inhibitor, such as gefitinib, erlotinib, and ecclinib.
Objective To explore the levels and the clinical significance of serum soluble Endoglin (sEng) and soluble Fms-like tyrosine kinase (sFlt-1) in patients with preeclampsia (PE). Methods Ninety-six patients with PE were included from June 2009 to June 2014. The patients were divided into mild PE group (n=54) and severe PE group (n=42), while 40 healthy pregnant women were in the control group. The general situation and laboratory testing were recorded and the serum levels of sEng and sFlt-1 were detected. All patients were routinely followed up with the recording of delivery and neonatal situation. Results The sEng and sFlt-1 levels were highest in the severe PE group [(7345.02±772.73) and (866.08±203.24) ng/L], which was followed by mild PE [(5 547.08±564.06) and (603.99±138.37) ng/L] and control group [(1 840.93±300.71) and (252.68±83.03) ng/L] (P<0.01). Levels of sEng were significantly correlated with sFlt-1 in both mild and severe PE groups. There were significantly correlations between sEng and sFlt-1 in mild or severe PE group respectively. The level of sEng and sFlt-1 was considerably positively correlated with mean arterial pressure, 24-hour urinary protein, serum creatinine, fibrinogen, umbilical artery shrink/diastole and resistance index value, but negatively correlated with prothrombin time, birth weight and the placenta weight (P<0.05). PE patients with sEng of <5 000 ng/L and sFlt-1 levels of <700 ng/L had the risk of severe complications of 6.8% and 14.0%; while patients with sEng of ≥5 000 ng/L and sFlt-1 of ≥700 ng/L had the ratio fo 40.4% and 37.0% respectively (P<0.01). Conclusion Serum levels of sEng and sFlt-1 in PE patients indicate that the severity of disease and outcomes of pregnancy.
Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes, and it is the main cause of vision loss in diabetic patients. Angiopoietin (Ang), a superfamily of secreted proteins, is a vascular growth factor that regulates the stability of vascular environment, participates in angiogenesis and repair, and lipid metabolism. It plays an important role in the development of DR and has become a new target for the treatment of diabetic retinopathy. With the in-depth study of Ang and the research and development of various drugs for Ang, it is expected to bring new ideas and strategies for the treatment of DR in the future.
ObjectiveTo summarize the biological function and molecular regulation mechanism of serine threonine tyrosine kinase 1 (STYK1) in tumor occurrence and development. MethodThe relevant literature about STYK1 and tumor progression in recent years was searched and reviewed. ResultsThe expression of STYK1 was up-regulated in a variety of tumors and was related to the prognosis. STYK1 might regulate the proliferation, apoptosis, migration, metastasis, aerobic glycolysis, drug resistance and other biological functions of tumor cells through MEK/ ERK, PI3K/AKT, JAK/STAT and their targeting proteins, and promote the malignant progress of tumors. Conclusion STYK1is expected to become a new target for the treatment of malignant tumors, but the molecular mechanism of its regulation of tumor progression and its upstream regulators need to be further explored.