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.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.
3.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
4.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.
5.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
6.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.
7.Application of sentinel lymph node biopsy assisted by 99Tcm-IT-Rituximab in cutaneous malignant melanoma of limbs
Jiayong LIU ; Zhiwei FANG ; Zhengfu FAN ; Chujie BAI ; Ruifeng XUE ; Shu LI ; Lu ZHANG ; Tian GAO
Chinese Journal of Clinical Oncology 2014;(21):1379-1382
Objective:To evaluate the accuracy and feasibility of sentinel lymph node biopsy (SLNB) marked by 99Tcm-IT-Ritux-imab and to discuss the clinical value of the method in diagnosis and treatment of cutaneous melanoma. Methods:A total of 67 patients with cutaneous malignant melanoma received 99Tcm-IT-Rituximab-tagged SLNB from March 2008 to March 2012. Lymphoscintigra-phy was conducted 30 min to 1 h after intra-dermal injection of 99Tcm-IT-Rituximab. Subsequently, the surgery of SLNB was carried out using gamma probe. The detection and positive rates of SLNB were counted. The relationship between the status and the clinical features of the sentinel lymph node (SLN) was analyzed, such as the T stage, ulceration, age, gender, and location. The influence of SLN status on overall survival (OS) and disease-free survival (DFS) was evaluated. Results:SLNs were detected in all the 67 patients by SPECT and gamma detector, with detection rate of 100%. Fifteen patients had SLN metastasis, and the positive rate was 22.4%. Chi-square indicates that SLN metastasis is associated with age, T stage, and ulceration (P<0.05). A total of 63 patients were followed up for 24-69 months, and the median follow up time was 43 months. Kaplan-Meier survival analysis shows that both OS and DFS in the SLN-negative group are better than those in the SLN-positive group (OS:93.9%vs. 57.1%, P<0.01;DFS:79.6%versus 28.6%, P<0.01). Cox-regression multiple factors analysis suggests that both SLN status and T stage are independent factors that affect the DFS of malignant melanoma. Conclusion:SLNB assisted by 99Tcm-IT-Rituximab can well reflect the state of lymph node metastasis and is es-sential for accurate staging, prognosis judging, and treatment guiding. Its operation procedure is simple with high accuracy, and the im-aging status is stable. Therefore, it is convenient and feasible as a means of SLNB.
8.Clinical features and prognosis of 25 cases of soft tissue sarcoma with soft tissue me-tastasis
Tian GAO ; Zhengfu FAN ; Jiayong LIU ; Chujie BAI ; Ruifeng XUE ; Shu LI ; Lu ZHANG ; Zhiwei FANG
Chinese Journal of Clinical Oncology 2017;44(1):36-40
Objective:To explore the outcome of soft tissue sarcoma (STS) on patients with soft tissue metastasis. Methods:We ana-lyzed 25 STS patients with soft tissue metastasis primarily localized on extremity and trunk. The study was conducted from June 2010 to June 2016 by retrospective analysis of the clinical and pathological characteristics of the patients. The assessed endpoints were overall survival. Results:Six patients (24%) had synchronous soft tissue metastasis, and 19 patients (76%) had metachronous metasta-sis. The average time for primary tumor recession of metastatic lesions was 45.3 months. Metastases were most common in parts of the trunk in 18 patients (72%), followed by the head and neck in 5 patients (20%). Eleven patients (44%) with lung metastasis had poor prognosis. Conclusion:STS occurred more rarely in soft tissue metastasis than in pulmonary metastasis. Neoadjuvant chemotherapy and surgical treatment were the major therapies employed. Targeted therapy as a new treatment rendered good results.
9.Expression of ubiquitin editing enzyme A20 and its pathway in steatotic hepatocytes and monocytes
Luoyan AI ; Qingqing XU ; Changwei WU ; Dazhi SU ; Xiaohan WANG ; Zhiwei CHEN ; Zhuping FAN
Chinese Journal of Digestion 2015;35(4):247-251
Objective To investigate the changes of A20 expression stimulated by free fatty acids (FFA) and its pathway.Methods HepG2 cells and U937 cells were stimulated by 0.5 mmol/L mixed FFA.The expression of A20,phosphor-p65 and phosphor-IκBα of neclear factor (NF)-κB pathway and phosphor-c-Jun N-terminal kinase (JNK),JNK,phosphor-extracellular signal-regulated kinase (ERK),ERK,phosphor-p38 and p38 of mitogen-activated protein kinase (MAPK) pathway were detected by Western blotting.The level of interleukin (IL)-12p,IL-1β,tumor necrosis factor (TNF)-α,IL-6,IL-10 and IL-8 cytokines in the supernatant of cell culture were detected by flow cytometry.T-test was performed for statistical analysis.Results The level of A20 changed along with the stimulated time of FFA.NF-κB and MAPK pathways were activated after FFA stimulation.The secretion of IL-6 and IL-8 increased after HepG2 cells stimulated by FFA and both reached peak at 24 hour.Compared with control group,the difference in IL-8 was statistically significant ((423.8 ± 8.9) pg/mL vs (12.4 ± 4.5) pg/mL,t=41.28,P<0.01).The difference in IL-6 was also statistically significant ((4 082±423.6) pg/mL vs (52.9±29.5) pg/mL,t=9.49,P<0.01).After U937 cells were stimulated by FFA,the secretion of IL-8 increased compared with control group.And in a certain period of time the secretion was time dependence.The maximum secretion of 24 hours was (200.6±5.7) pg/mL vs (5.0±3.9) pg/mL,and the difference was statistically significant (t=28.16,P<0.01).IL-10,IL-12p,IL-1β and TNF-α were detected.Both NF-κB pathway and MAPK pathway were detected.Conclusions The in vitro FFA mediated steatotic cell model could induce the expression change of A20 and secretion of inflammatory cytokines.NF-κB and MAPK pathways involved in the response to FFA in HepG2 cells and U937 cells.
10.The protective effect of sodium pyruvate solution to intestinal barrier in hemorrhagic shock rats by intraperitoneal resuscitation
Xiaozhou WANG ; Xiaoguang LU ; Xin KANG ; Zhiwei FAN ; Shuai GUO ; Zhengkai LIANG
Chinese Journal of Emergency Medicine 2014;23(10):1120-1124
Objective To study the protective effect of sodium pyruvate solution to intestinal barrier in Hemorrhagic shock rats by intraperitoneal resuscitation.Methods A total of 40 Male SD ratswere healthy and clean,were randomly (random number) divided into four groups:sham operation group (group Ⅰ),hemorrhagic shock model group (group Ⅱ),the recovery of the compound sodium chloride intravenous + intraperitoneal recovery of the PD-2 liquid group (group iiⅢ),the recovery of the compound sodium chloride intravenous + sodium pyruvate abdominal recovery group (group Ⅳ) (n =10).In addition to the group Ⅰ,the other three groups are used the HS model by The Wiggers improvement prepared,group Ⅲ,Ⅳ were used the same amount of intravenous recovery,At the same time to the abdominal cavity were respectively injected 20 mL 2.5% PD-2 liquid and 20 m 2.5% sodium pymvate solution.After 2 h,each group were taken arterial blood measured arterial blood gases (pH,PaCO2,PaO2) and D-lactic acid,small intestine specimens under the light microscope to observe the morphological changes of the rat small intestinal mucosa.Results Blood gas analysis:group Ⅲ and Ⅳ was significantly increased compared with group Ⅱ in pH levels and PaO2 content (P < 0.01),and comoared to group Ⅲ,pH levels and PO2 levels of group Ⅳ increased more significantly (P < 0.05) ; D-LA content:Group Ⅲ,Ⅳgroup is significantly lower than group Ⅱ (P < 0.01) ; compared with group Ⅲ and group Ⅳ,D-LA significantly decreased (P < 0.05).Light microscope,the group Ⅱ,the rat small intestine layer of a high degree of villous edema,submucosal vascular collapse within the lamina propria glands focal area of necrosis,and large areas of mucosal villi necrosis,defects; group Ⅲ and group Ⅳof small intestinal damage compared to group Ⅱ significantly reduced; Ⅳgroup of the rat small intestine villi edema,lodging and the degree of necrosis in group Ⅲ.Intestinal epithelial damage index score:the Ⅳ group than in group Ⅱ and Ⅲ group (P < 0.01 or P < 0.05).Conclusions The venous recovery and intraperitoneal resuscitation can significantly reduce the plasma D-LA content of hemorrhagic shock in rats,correct acidosis,increase the oxygen partial pressure ; and intestinal mucosal barrier function,the protective of sodium pyruvate solution is better than the PD-2 liquid.