1.Inhibition of Src tyrosine kinase on subcutaneously transplanted tumor of human lung adencarcinoma hi mice and its mechanism
Rui ZHENG ; Xiaosong QIN ; Wenjie LI ; Sha WU ; Jian KANG
Cancer Research and Clinic 2011;23(5):299-302
Objective To study the effect of Src tyrosine kinase inhibition on subcutaneously transplanted tumor of human lung adenocarcinoma in mice and its mechanism. Methods For the subcutaneously transplanted tumor model, A549 cells or PC-9 cells were inoculated into SCID mice by subcutaneous injection. Immunohistochemistry was used to show the effect of Src tyrosine kinase inhibition on proliferation index (Ki-67 staining) and microvessel density (CD31 staining) of subcutaneously transplanted tumor of human lung adenocarcinoma in mice. Results Subcutaneously transplanted tumor of PC-9 cells was sensitive to src tyrosine kinase inhibitor. There was significant difference between treatment group and control group (P <0.01). There was significant difference between the two treatment group too (P <0.01). Stopping treatment for 1 week, the inhibition rate of tumor growth were 33.19 % and 84.79 % in 10 mg·kg-1·d-1 and 50 mg·kg-1·d-1 treatment group, respectively. The same treatment was less effective to subcutaneous tumors produced by A549 cells. Treatment with 50 mg·kg-1·d-1 Src tyrosine kinase inhibitor significantly reduced the proliferation index of subcutaneously transplanted tumor produced by PC-9 cells (P<0.01) and tended to reduce the proliferation index of subcutaneously transplanted tumor produced by A549 cells (P >0.05). Treatment with 50 mg·kg-1·d-1 Src tyrosine kinase inhibitor significantly reduced micro vascular density in both PC-9 and A549 induced subcutaneous tumors (P <0.05). Conclusion Inhibition of Src tyrosine kinase could suppress the progression of subcutaneously transplanted tumor, not only by the inhibition of cell proliferation of lung adenocarcinoma cells directly, but also by the inhibition of angiogenesis indirectly.
2.Valproic acid enhances myeloma cell sensitivity to natural killer cell-mediated lysis and its mechanism
Xueping SHA ; Wei JIANG ; Xiaosong WU ; Minjie GAO ; Hongmei WANG ; Jumei SHI
Journal of Leukemia & Lymphoma 2013;22(8):474-479
Objective To investigate the effect of valproic acid (VPA) on NKG2D-ligand expression in ARK,OPM2 human myeloma cell lines and their sensitization to natural killer (NK) cell-mediated Killing.Methods Different concentrations of VPA from 0-5.0 mmol/L were used to treat ARK,OPM2 cells respectively,then the cell viabilities were tested by flow cytometry (FCM).Real-time quantitative-PCR and FCM were used to detect the changes in mRNA,protein levels of NKG2D-ligand respectively in the two cell lines treated with 1 mmol/L VPA for 48 hours.The calcein-release-assay (CARE-LASS) was carried out to detect cytotoxic changes of NK cells against mydoma cells after VPA treatment.Results VPA induced the expression of MICA/B,ULBP2 (P < 0.05) and in turn enhanced the NK cytotoxicity on myeloma cells.The enhancing effect of VPA was blocked by NK cells pretreated with anti-NKG2D mAb (P < 0.05).The primary mechanism of NK cell killing of myeloma cells was perforin/granzyme-mediated.Conclusion VPA can induce the expression of MICA/B,ULBP2 in ARK,OPM2 cells,thereby enhancing the cytotoxicity against myeloma cells,which implies a new mechanism of anticancer approach and may be a new approach in myeloma immunotherapy.
3.Cluster management in secondary hydrocephalus
Jun LIU ; Xianjian HUANG ; Jie GAO ; Xiaosong SHA ; Jiehua ZHANG ; Dongliang ZHU ; Chuwei WU ; Gaojian SU
Chinese Journal of Neuromedicine 2023;22(5):507-512
Objective:To explore the clinical value of cluster management in secondary hydrocephalus.Methods:Seventy-seven patients with secondary hydrocephalus admitted to Department of Neurosurgery, Shenzhen Second People's Hospital from January 2016 to June 2021 were chosen; they were divided into traditional management group ( n=30) and cluster management group ( n=47) according to different management methods. Patients in traditional management group accepted craniocerebral CT and 3 consecutive times of cerebrospinal fluid tests, and normal results were achieved and then ventriculoperitoneal shunt (VPS) was performed. In patients from the cluster management group, on the basis of management treatment, cranial plain and enhanced MRI and DNA metagenomic next generation sequencing of cerebrospinal fluid were performed before surgery, and rapid test of cerebrospinal fluid and ventriculoscope observation were performed during surgery; after exclusion of intracranial infection, VPS was performed. The differences of shunt failure rate were compared between the two groups and the positive rates of intracranial infection detected by above 4 methods were compared in the cluster management group. Results:There was significant difference in shunt failure rate between the cluster management group and traditional management group (2.1% vs. 20.0%, P<0.05). The positive rates of intracranial infection by DNA metagenomics (61.7%) and ventriculoscopy (68.1%) were significantly higher than those by preoperative cranial plain and enhanced MRI (14.9%) and rapid test of cerebrospinal fluid (6.4%, P<0.05). Conclusion:Cluster management can effectively decrease the VPS failure rate in secondary hydrocephalus; DNA metagenomics and ventriculoscopy have high efficiency in detecting intracranial infection.