1.Advances in molecular targeted therapy for soft tissue sarcomas
Tian GAO ; Zhengfu FAN ; Zhiwei FANG
Chinese Journal of Clinical Oncology 2017;44(1):7-13
Sarcomas are tumors of mesenchymal origin that account for approximately 1%of human cancers. There are at least 60 dif-ferent subtypes of soft tissue sarcoma (STS). However, most tumor types are highly malignant tumors that lack an optimal therapeutic agent. Although gastrointestinal stromal tumor (GIST) responds well to imatinib, other types of STSs remain challenging because of their heterogeneous genetic and clinical features and poor prognosis. In recent years, the field of molecular targeted therapy has pro-gressed rapidly. Patients with advanced disease can receive individualized treatment to improve their quality of life. This review focus-es on the targeted therapies that have been evaluated for advanced non-GIST STS. Other promising novel therapeutic agents that are currently in the early phases of investigation are also presented.
2.The clinical study on myocardial protection in aged patients undergoing coronary artery bypass grafting
Guohua FAN ; Zhiwei WANG ; Zhongfan TU ; Shangzhi GAO ; Zhifu MAO ;
Chinese Journal of Geriatrics 2003;0(11):-
Objective To compare the myocardial protective effect between off pump coronary artery bypass(OPCAB) and on pump coronary artery bypass in the aged. Methods Four five patients were randomly divided into 3 groups:off pump coronary artery bypass (n=15),tepid blood cardioplegia group(n=15) and cold blood cardioplegia group (n=15).There was no statistical difference in heart function,sex,age and lesion of coronary artery .Venous blood samples were taken for determineing the serum concentration of creatine kinase MB isoenzyme(CK MB),troponin I perioperatively and the clinical situations were observed postoperatively. Results CK MB,troponin I release in beating group during and after bypass was lower than that in on pump groups( P
3.Transplantation of bone marrow mesenchymal stem cells harboring fusing gene of enhanced green fluorescent protein and human insulin gene in treatment of diabetic mice
Xiangjun FAN ; Yuan ZHOU ; Mingyan ZHU ; Zhiwei WANG
Academic Journal of Second Military Medical University 1999;0(12):-
Objective:To construct a retroviral vector carrying both enhanced green fluorescent protein(EGFP) and human insulin gene for transfecting the bone marrow mesenchymal stem cells (BMSCs),and to observe the treatment effect of transfected BMSCs after transplanted into diabetes mice.Methods:Two gene segments of insulin-IRES-EGFP and IRES-EGFP were obtained by overlap extension PCR technology,and then the 2 segments were cloned into retroviral vector (pMSCV).The vectors were used to transfect BMSCs after packaged with PT67 cells.The expression of EGFP was observed by inverted fluorescence microscope and the expression of insulin gene was examined by RT-PCR in the infected BMSCs.The transfected BMSCs with 2 viruses were transplanted into diabetic mice separately.The blood glucose levels and body weights of mice were examined in 2 groups,and the results were compared with those of normal control group.Results:The recombinant retroviral vectors pMSCV-insulin-IRES-EGFP and pMSCV-IRES-EGFP were successfully constructed.The BMSCs infected by both vector stably gave out green fluorescence under microscope; the cells infected with pMSCV-insulin-IRES-EGFP also stably expressed human insulin gene.The blood glucose level of the mice transplanted with BMSCs transfected with pMSCV-insulin-IRES-EGFP was significantly lower than that transplanted with BMSCs transfected with pMSCV-IRES-EFGP (P
4.Development of regional medical big data based on information sharing
Yifan FAN ; Yanjun WANG ; Jianming CHEN ; Zhiwei XIA
Chinese Journal of Medical Library and Information Science 2016;25(12):7-10
The significance and contents of regional medical cloud construction based on information sharing were summarized according tothe three-circle theory, and the status quo and difficulties of the first diagnosis system, with the implementation of health information system for Xiamen residents as an example, and suggestions were pro-posed for the development of regional medical big data.
5.Biomechanical factors in the design of new femoral neck screw in children
Xuanhuai HUANG ; Ying LIAO ; Weijie FAN ; Zhiwei CHEN
Chinese Journal of Tissue Engineering Research 2013;(39):6954-6961
BACKGROUND:As the epiphyseal plate has an important role in the growth and development of femur, the design of internal fixation should avoid the damage to the epiphyseal plate. Therefore, the positioning of pediatric femoral epiphyseal plate is particularly important.
OBJECTIVE:To investigate the biomechanical property of the new femur neck screw internal fixation in treatment of children femoral neck fracture.
METHODS:Twelve femurs were col ected from six fresh children cadavers provided by Dissecting Room of University of South China. After exclusion of bone disease with X-ray film, three new children femoral neck screws and three Kirschner wires with the diameter of 2.0 mm were used for fixation. The biomechanical tests were conducted to detect the axial compression and torsion stiffness.
RESULTS AND CONCLUSION:In the children femoral neck screw group, the axial compression stiffness and torsion stiffness under the torsional torque of maximum 3 N?m were (190.74±20.88) N/mm and (0.18±0.045) N?m/° respectively;(138.95±15.19) N/mm and (0.120±0.036) N?m/° respectively in the Kirschner wire group;there were significant differences in the axial compression stiffness and torsion stiffness between two groups (P<0.05). The results showed that the compressive strength and torsional capacity of the children femoral neck screw were strong than those of Kirschner wire. The experiment suggested that the femoral neck screw for children is a new type of ideal internal fixation device which consist with the anatomical features of children proximal femur and can meet the requirement of children femoral neck fracture with good biomechanical property.
6.In vitro co-culture induced mesenchymal stem cells differentiate to islet cell
Haoliang SHEN ; Zhiwei WANG ; Mingyan ZHU ; Xiangjun FAN ; Yuhua LU
Chinese Journal of Pancreatology 2008;08(6):397-400
Objective To observe the effects of differentiation of mature islet cells of mice on marrowmesenchymal stem cells (mMSCs). To provide transplant source for islet cell transplantation in the treatment of diabetes. Methods The culture, isolation and passage of mMSCs was performed by using patch wall, cell shape was observed by confocal microscope, and flow cytometry analysis was used to determine their biological characteristics. The type Ⅳ collagenase was injected into common bile duct to digest the pancreas, and then gradient centrifugation was used to isolate islet cells. The transwell co-culture system was used for third generation of mMSCs and isolated islet cells, then inversion microscope was used to observe the cell growth and morphological changes, immunochemistry methods was applied to detect the expression of insulin in mMSCs, and insulin release test was performed to determine the secretion of insulin. The control group consisted of cultured mMSCs alone. Results The cells from mouse bone marrow were found to be in long spindle shape with large volume after 48 hours in culture. One week later the cells grew in the form of colony with serial subcultivation. The cell surface molecules including Sca-l, CD29, CD44, CD105 were positive with high level of expression;while the cell surface molecules including CD34, CD45 were negative, all of these results confirmed that the ceils were mMSCs. After 7 days of coculture with mice islet cells, part of mMSCs cells were positively stained by insulin immunohistochemisty, the insulin secretion was (16.83±0. 15)μIU/ml.Conclusions After cocultured with islet cells, mMSCs isolated from mouse bone marrow could differentiate into islet like cells. These cells may be used in the islet cells transplantation in the treatment of diabetes, which provided a solution to the problems of donor-shortage and immunologic rejection.
7.Influence of streptozocin's dose on inductive effect of diabetes in C57BL/6J mice
Chenliang SUN ; Mingyan ZHU ; Zhiwei WANG ; Xiangjun FAN ; Yuhua LU ; Haoliang SHEN
Chinese Journal of Pancreatology 2009;9(1):24-26
Objective To investigate the influence of streptozocin (STZ)'s dose on the inductive effect of diabetes in C57BL/6J mice, and investigate the dose-effect relationship and the optimal dose range. Methods 145 C57BL/6J mice were randomly divided into 9 diabetic groups (group A to group 1, n = 15 in each group) and I control group (n = I0) to receive intraperitoneal injection of STZ with the dosages of 30, 60, 80, 100, 120, 150, 180, 210, 240 mg/kg and same amount of buffer solution,respectively. Changes of blood glucose, body weight, survival rate at 45 day and serum insulin level were monitored, and the relationship with STZ doses was analyzed. Pancreas and kidneys of the mice were removed for morphological examination, and immunohistochemistry was used for determination of insulin in pancreas and CD<,68> in kidneys. Results Compared with control group, blood glucose in group C ~G increased significantly; body weigh, insulin level decreased significantly (P < 0.05), and the STZ dose was positively correlated with mean blood glucose (r = -0.984, P < 0.05) and was negatively correlated with mean serum insulin levels (r = 0.994, P <0.05). The diabetes modeling rates in group C ~ G (86.7% ~ 100%) were higher than those of group A and B (0 and 40%, P<0.05). At the 45th day, the survival rates of group C ~G (46.7% ~ 73.3%) were higher than those of group H and 1 (13.3% and 0, P <0.05). There was no obvious injury of pancreas and kidneys in group B, whereas, in group C and G, pancreatic island atrophy and decreased insulin secretion were observed; deposits of extracellular matrix and macrophage increased in the mesangium were also present. Conclusions 80 ~ 180 mg/kg of STZ dose was ideal for establishing diabetes model in C57BL/6J mice. Within this range, the modeling rate and survival rate was higher, and target organs injury was typical. The STZ dose was positively correlated with blood glucose and negatively correlated with serum insulin levels.
8.L-arginine effects on osteoporotic fracture healing and blood biochemistry
Shixu ZHANG ; Kaosheng LU ; Changhao SHI ; Yan FAN ; Zhiwei YAO ; Yunsheng YIN
Chinese Journal of Tissue Engineering Research 2013;(28):5120-5125
BACKGROUND: Nitric oxide plays an important role in bone metabolism. However, the effects of different doses of L-arginine, nitric oxide substrate, on the healing of osteoporotic fractures remain unclear. OBJECTIVE: To investigate the influence of different doses of L-arginine on the healing of osteoporotic fractures and blood biochemistry in rats. METHODS: A total of 50 female Wistar rats, aged 6-month-old, were randomly divided into sham-surgery (n=10) and osteoporosis (bilateral ovariectomy, n=40). After osteoporosis model was established, left middle femoral fractures were made in al 50 rats, and the osteoporosis group was further divided into four groups, low, middle and high dose of L-arginine, and control groups. The L-arginine groups were intraperitoneal y injected with 1, 3, and 5 mg/kg L-arginine at the second day fol owing surgery, while the control and sham-surgery groups were injected with the same volume of normal saline. At 8 weeks, the lumbar and cal us bone mineral density, serum nitric oxide, and nitric oxide synthase were detected. Meanwhile, the bone cal us histological examination was conducted. RESULTS AND CONCLUSION: During fracture healing, osteoporosis rats showed a low level of serum nitric oxide and nitric oxide synthase compared with normal fractured rats (P < 0.05). L-arginine can improve the concentration of serum nitric oxide and nitric oxide synthase in osteoporosis rats. Moreover, middle dose of L-arginine can increase the cal us and lumbar spine bone mineral density of osteoporosis rats, so the number and continuity of bone trabecula were enhanced. These findings suggest that middle dose of L-arginine (3 mg/kg) can promote healing process of osteoporotic fractures and improve osteoporosis.
9.Doxorubicin induces enrichment of stem-like cells in osteosarcoma by activating Notch signaling
Ling YU ; Tian GAO ; Zhengpei ZHANG ; Chunjie TAO ; Weichun GUO ; Zhiwei FANG ; Zhengfu FAN
Chinese Journal of Clinical Oncology 2017;44(11):527-531
Objective:Cancer stem cells (CSCs) are resistant to chemotherapy. Our study aimed to investigate the stem cell-like proper-ties of doxorubicin-resistant osteosarcoma cell line 143B and its correlation with Notch signaling. Methods:We generated doxorubicin-resistant osteosarcoma cells by treating them with 2μm doxorubicin. Stem cell-like properties such as morphology change, Stro-1/CD117 double positive ratio, stem cell-related gene expression, sphere formation efficiency, and EMT character were assessed on day 5 after doxorubicin withdrawal. Notch receptor and its target genes were examined using qPCR and Western blot analysis. The stem cell-like properties of doxorubicin-resistant osteosarcoma cells were assessed when pretreated with Notch inhibitor or vehicle. The an-ti-tumor effect of Notch inhibitor was tested using a xenograft model. Results:Doxorubicin-resistant osteosarcoma cells were enriched in Stro-1+/CD117+cells, which showed obvious increased expression of stem cell-related genes, and exhibited enhanced spheroid for-mation and evident mesenchymal characteristics unlike doxorubicin-sensitive cells. qPCR and Western blot assays showed that Notch intracellular domain 1 (NICD1) and target genes Hes1 and Hey1 were upregulated in doxorubicin-resistant osteosarcoma stem cells compared with those in vehicle cells. Furthermore, pretreatment with a γ-secretase inhibitor (GSI) to prevent Notch signaling en-hanced chemo-sensitivity and inhibited doxorubicin-enriched osteosarcoma stem cell activity in vitro. Finally, the Notch inhibitor pre-vented tumor growth in mice xenograft models. Conclusion: Doxorubicin induced the enrichment of osteosarcoma stem-like cells through Notch signaling, and inactivation of Notch could be useful for overcoming drug resistance and eliminating osteosarcoma.
10.Phosphorylation PKC? participates in apoptosis of PC12 cells induced by 6-hydroxydopamine
Zhiwei LI ; Yanqiao ZHANG ; Ying FAN ; Hulun LI ; Yina ZHANG ; Changqing XU
Chinese Journal of Pathophysiology 1989;0(06):-
AIM: To observe the effect of phosphorylation protein kinase C delta (PKC?) on the procedure of PC12 cells apoptosis induced by 6-hydroxydopamine(6-OHDA) and to investigate the potential molecular pathogenesis of Parkinson disease.METHODS: TUNEL staining and transmission electron microscope were applied to measure apoptosis when dopaminergic PC12 cells exposed to the excitomotors and inhibitors of PKC before 6-OHDA for 18 hours. The expression of phosphorylation of PKC? was detected by Western blotting. RESULTS: PMA, an activating agent of PKC?, significantly increased PC12 cell apoptosis induced by 6-OHDA. Rottlerin, an inhibitor of PKC?, protected PC12 cells apparently. As contrast, bisindolylmaleimide I, an inhibitor of general PKC and G6976, the inhibitor of calcium-dependent PKC, did not show any protective role. CONCLUSION: The phosphorylation PKC? is one of the important links in the process of PC12 cell apoptosis induced by 6-OHDA. PKC? may directly participate in neurodegeneration process in parkinsonian.