1.Progress in the Diagnosis and Treatment of Dedifferentiated Chondrosarcoma
Guowen WANG ; Xiaodong TANG ; Wei GUO
Chinese Journal of Clinical Oncology 2010;37(1):56-59
Dedifferentiated chondrosarcoma(DDCS)comprises approximately 10%of all chondrosarcomas and has the worst outcome with a 5-year survival of 10%.The preferred localizations are the femur,humerus and pelvis.DDCS represents a special form of chondrosarcoma characterized by the presence of well-differentiated cartilaginous component in juxtaposition with malignant mesenchymal tumor of high-malignancy grade.The diagnosis of DDCS is highly complicated,requiring detailed radiological and histopathological evaluation as well as precise bioptic technique.The dedifferentiated component is typically a high-grade sarcoma(usually grade 3 or 4),which can be either an osteosarcoma,a malignant fibrous histiocytoma or an anaplastic spindle cell sarcoma.In approximately one-third of the radiographs,one-third of the MR images,and one-half of the CT scans, the tumors demonskates bimorphic features.Recently,array-based comparative genomic hybridization(array-CGH)studies have been performed on frozen chondrosarcoma(including DDCS)specimens.There is a statistically significant association between high-grade tumor(grade Ⅲ and dedifferent ated)and the recurrent genetic deletions at 5q14.2~q21.3,6q16~q25.3,9p24.2~q12,and 9p21.3.One of the most commonly deleted regions of DDCS involved chromosome 9.Earlier investigations of DDCS showed p53 mutation and p53-LOH in the anaplastic component.It is also accompanied by Rt-LOH.P161NK4 and E-cadherin promotor methylation were observed in the low grade chondroid compartment of DDCS.While p161NK4,FHIT,and E-cadherin were methylated in highly malignant osteosarcomatous compartment of the tumor.Surgical resection of the tumor within wide or radical margins is the most important treatment.The value of neoadjuvant or adjuvant therapy remain uncertain.Several new drug targets have been identified and phase Ⅱ studies are currently ongoing.Current phase Ⅱ trials open for DDCS patients used the following medicine:apomab(proapoptotic selective agonist of Ap02L/TRAIL death receptor),perifosine(serine/threonine kinase Akt inhibitor),dasatinib(multitargeted small-molecule tyrosine kinase inhibitor),and the combination of gemcitabine and docetaxel.More recently,several phase Ⅰ studies have reported incidental responses of DDCS to newer targeted agents,such as histone deacetylase and vascular endothelial growth factor antisense oligodeoxynucleotide.The prognosis for patients with DDCS remains poor. The poor prognosis of the DDCS is determined by nonchondroid high grade component caused by invasive growth and formation of metastases.Therefore,early diagnosis and prompt surgical treatment may improve the outcome.
2.Expression and biological significance of Runx2 in dedifferentiated chondrosarcoma cell line
Xinchang LU ; Xiaodong TANG ; Wei GUO ; Guowen WANG
Cancer Research and Clinic 2010;22(4):231-234
Objective To detect the different expression of Runx2 in dedifferentiated chondrosarcoma and conventional chondrosarcoma, and to investigate the role of Runx2 in the occurrence and development of dedifferentiated chondrosarcoma. Methods Dedifferentiated chondrosarcoma cell line NDCS-1 and normal chondrosarcoma cell line SW1353 were cultured, then mRNA and total cellular protein were extracted.RT-PCR Western blotting, and immunocytochemistry were used to detect the expression of Runx2.Immunohistochemistry was used to test Runx2's expression in the dedifferentiated chondrosarcoma specim ens that confirmed by pathology. Results Runx2 was high expression in dedifferentiated chondrosarcoma cell line and high-grade component of dedifferentiated chondrosarcoma tissues. Conclusion The high expression of Runx2 in dedifferentiated chondrosarcoma is involved in the occurrence and development of dedifferentiated chondrosarcoma.
3.Differential Expression of Sox9 in Conventional Chondrosarcoma and Dedifferentiated Chondrosarcoma
Guowen WANG ; Xiaodong TANG ; Wei GUO ; Changliang PENG ; Hui ZHAO
Chinese Journal of Clinical Oncology 2010;37(5):250-253
Objective: To investigate the differential expression of Sox9 in conventional chondrosarcoma,dedifferentiated chondrosarcoma and normal cartilage. Methods: We reported 12 cases of chondrosarcomas,which were initially diagnosed as chondrosarcomas(6 cases of conventional chondrosarcoma and 6 cases of dedifferentiated chondrosarcoma)at Peking University People's Hospital between January 2003 and January 2007.We used genechip method to identify difierentially expressed genes involved in conventional chondrosarcoma,dedifferentiated chondrosarcoma and in normal cartilage(6 cases)and found thousands of differentially expressed genes after extensive statistical analysis.With Sox9 which played crucial roles in the process of both differentiation and maturation of chondrocyte as a candidate,we used Real-time PCR,Westem blot and immunohistochemistry to confirm the results found by gene chip. Results: DNA microarray results showed that Sox9 was up-regulated about 1.6 times in conventional chondrosarcoma compared with that in normal cartilage.But in dedifferentiated chondrosarcoma,the expression level of Sox9 was significantly down-regulated,0.082 times of that in normal cartilage.Real-time PCR results showed that the expression levels of Sox9 mRNA in conventional chondrosarcomas and dedifferentiated chondrosarcomas were 1.68±0.119 and 0.088±0.017,respectively.Sox9 protein level was significantly higher in humen conventional chondrosarcomas than that in normal cartilage.Sox9 protein level in dedifferentiated chondrosarcomas was significantly lower than that in normal cartilage tissue.All of the 6 cases of conventional chondrosarcomas showed diffuse and strong staining of Sox9.However,Only scattered staining was observed in dedifferentiated chondrosarcomas. Conclusion: Compared with that in normal cartilage,Sox9 expression is up-regulated in conventional chondrosarcomas and down-regulated in dedifferentiated chondrosarcomas.Decrease of Sox9 expression in dedifferentiated chondrosarcoma is correlated with poor survival,indicating that Sox9 may serve as a molecular prognostic marker for chondrosarcomas and disease progression.
4.Clinical research on advanced liver cancer treated with percutaneous RFA cool-tip electrode under ultrasound guidance
Shixi CHENG ; Guowen YING ; Weidong XU ; Wei XI ; Ming ZHANG
Journal of Interventional Radiology 1992;0(01):-
Objective To evaluate the clinical efficacy and complications in the treatment of advance liver cancer under ultrasound guidance with percutaneous RFTI-1 TM-cold cycle RF tumor ablation apparatus produced by Nangjing TianMa high-tech Company limited. Methods 25 patients of advance liver cancer, including 8 cases of metastatic liver cancer, 17 of primary hepatic carcinoma, were treated with percutaneous RFA cool-tip electrode under Ultrasound guidance 1 to 2 times. Eight of the patients prior to RFA were treated with TACE of individually three times for each. The postoperative efficacy was evaluated by enhanced CT. Results 10 lesions were completely necrotized and the majority parts of another 15 lesions were also under necrosis. Follow-up of six months, all patients are still alive with marked improvement of life quality. Conclusion The short-term efficacy of percutaneous Ultrasound-guided RFA with cool-tip electrode for treating advance liver cancer is quite satisfied, worthy to be recommended.
5.Lethal effects of nanoliposome encapsulated cisplatin on Saos-2 cells and its distribution in nude mice bearing human osteosarcoma xenografts
Guowen WANG ; Wei GUO ; Xiaodong TANG ; Changliang PENG ; Hui ZHAO
Journal of Peking University(Health Sciences) 2003;0(05):-
Objective:To investigate the killing effect of nanoliposome encapsulated cisplatin(NLE-CDDP) on human osteosarcoma cell line Saos-2 and explore the distribution of platinum(Pt) in tumor-bearing mice.Methods: Saos-2 cells were cultured at different concentrations of NLE-CDDP.MTT assay,inverted microscopic observation and flow cytometry assay(FCM)were used to observe the antiproli-ferative effect of NLE-CDDP on the human osteosarcoma cells.Antitumor effect of NLE-CDDP was determined using the xenografts models of human osteosarcoma cell Saos-2 in nude mice.The Pt concentration in the tissues of tumor-transplanted mice was determined by atomic spectrophotometer.Results: When treated at different concentrations of NLE-CDDP for 24-96 hours,the survival rate of Saos-2 cells decreased significantly(P
6.Survey of the training among community health service staff in Guangdong province
Weiguang YAO ; Guowen WEI ; Aiguang XU ; Liyan QIU ; Zhuo CHEN ; Hongyan YU
Chinese Journal of Medical Education Research 2011;10(9):1136-1138
ObjectiveTo learn the status quo of pre-job training,on-the-job training and the demands of training among community health service staff,and to provide evidence of continuing education.MethodsInvestigation was made by self-designed questionnaire in 335 community health service staff from ten service centers and seven service stations in four regions of Guangdong province.Results The rate of pre-job training and on-the-job training were lower than the training demands among community health service staff.The content of on-the-job training was varied and could meet the training needs.Training was maily done in superior hospitals and the main form of training was seminars and classroom teaching.ConclusionTraining efforts should be increased to meet the training demands.Training model should be innovated to improve the training effect.Hospital and community exchanges should be strengthened and the training system should be improved.
7.Endovascular interventional therapy of portal vein stenosis after pediatric liver transplantation
Zhiyuan ZHANG ; Long JIN ; Guang CHEN ; Tianhao SU ; Zhenchang WANG ; Zhijun ZHU ; Lin WEI ; Guowen XIAO
Chinese Journal of Interventional Imaging and Therapy 2017;14(4):210-213
Objective To evaluate the value of percutaneous transhepatic angioplasty in treatment of portal vein stenosis (PVS) after pediatric liver transplantation.Methods The data of 8 pediatric patients with PVS after liver transplantation were retrospectively evaluated.All cases were confirmed by portal vein angiography,and were treated with percutaneous transluminal angioplasty and/or percutaneous transluminal stent angioplasty.The effect of endovascular interventional therapy in 8 cases was analyzed.Results A total of 12 times of 8 patients received endovascular interventional therapy.The success rate was 66.67% (8/12).The clinical success rate of the first treatment was 62.50% (5/8).Three cases were treated with balloon dilation after the first balloon dilation,and there was no recurrence of PVS after operation in 2 cases.After the treatment of balloon dilation,stent angioplasty was performed in 1 case.There were no complications related to treatment in 8 cases.Conclusion Endovascular interventional treatment is a safe and effective way for PVS after pediatric liver transplantation.
8.Endovascular treatment of portal vein stenosis after pediatric liver transplantation for biliary atresia
Zhiyuan ZHANG ; Long JIN ; Guang CHEN ; Tianhao SU ; Zhenchang WANG ; Zhijun ZHU ; Lin WEI ; Guowen XIAO
Chinese Journal of Interventional Imaging and Therapy 2017;14(11):655-658
Objective To observe the value of endovascular treatment of portal vein stenosis (PVS) after pediatric liver transplantation for biliary artesia.Methods The data of 14 children with PVS after liver transplantation for biliary atresia were retrospectively evaluated.All children were confirmed by portal vein angiography,and were treated with 1-2 times of percutaneous transluminal angioplasty with or without percutaneous transluminal stent angioplasty.The effect of endovascular interventional therapy in 14 children was analyzed.Results A total of 14 children received 23 times of endovascular interventional therapy.The technical success rate of the first treatment was 82.61% (19/23).Ten children were treated with balloon dilatation,and stent angioplasty was performed in 4 children after balloon dilatation.These stents were not narrowed after implantation.There were no complications related to treatment in 14 cases.Conclusion Endovascular treatment for PVS after liver transplantation for biliary atresia is safe and effective.
9.Bone remodeling in the Masquelet-induced membrane model of rat femur by modulation of H-type vessels by total flavonoids of rhizome drynariae
Zhikui ZENG ; Wei XIONG ; Weidong LIANG ; Guowen QIAN ; Chaoyi LIANG ; Bin PAN ; Ling GUO ; Wenqiang WEI ; Xunxiang QIU ; Wenfang DENG ; Lingmei YUAN
Chinese Journal of Tissue Engineering Research 2024;28(32):5130-5135
BACKGROUND:Several studies have found that the total flavonoids of rhizome drynariae can promote neovascularization in the induced membrane,improve the biological properties of the induced membrane,and accelerate bone remodeling in the induced membrane,but the related molecular mechanisms still need to be further explored. OBJECTIVE:To explore the effect of total flavonoids of rhizome drynariae on bone remodeling in rat femoral Masquelet-induced membrane model by regulating H-type blood vessels. METHODS:Thirty-six male Sprague-Dawley rats were stratified by body mass and then randomly divided into blank group,model group and traditional Chinese medicine group,with 12 rats in each group.A 4-mm femoral bone defect model was established in all the rats.Bone defects in the model group and traditional Chinese medicine group were filled with polymethylmethacrylate bone cement.At 6 weeks after modeling,the tail bone of the rats was implanted in the blank group,as well as in the other two groups after removal of bone cement.The traditional Chinese medicine group was given 157.5 mg/kg per day of total flavonoids of rhizome drynariae at 3 days after bone implantation,while the model and blank groups were given the same amount of saline by gavage until the 8th week after bone implantation.Bone graft samples were taken for relevant testing at 8 weeks after implantation. RESULTS AND CONCLUSION:X-ray films showed that in the blank group,the fracture line in the defect area was clear,and only a small amount of bone callus formed;in the model group,the bone defect area still existed,where discontinuous cortical bone was visible;in the traditional Chinese medicine group,the defect area was filled with newborn bone tissues,the bone marrow cavity and part of the cortical bone formed,and the fracture line disappeared.Micro-CT scans showed that the amount of new bone in the defect area was low in the blank group,the number of bone trabeculae in the defect area was significantly increased in the model group,and a large amount of new bone tissue was filled in the bone defect area in the traditional Chinese medicine group.Hematoxylin-eosin staining results showed that in the blank group,only a small amount of new bone formed in the defect area and the quality of osteogenesis was poor;in the model group,there was more new bone tissue in the defect area,but some fibrous connective tissues were interspersed within the bone tissue;and in the traditional Chinese medicine group,a large amount of new bone formed in the defect area and the quality of osteogenesis was the best.CD31/Emcn immunofluorescence double-labeling staining results showed that the number of H-type blood vessels in the newborn bone tissue in the bone defect area of the blank group was sparse and sparsely distributed;compared with the blank group,there were more H-type blood vessels in the bone tissue in the bone defect area of the model group,and the blood vessels were distributed in relatively regular strips;the number of H-type blood vessels in the bone defect area of the traditional Chinese medicine group was the highest and the blood vessels were densely distributed.To conclude,the total flavonoids of rhizoma drynariae can upregulate the expression of H-type blood vessels to enhance the angiogenic-osteogenic effect,improve the osteogenic efficiency of the rat femoral Masquelet induced membrane model,and promote bone remodeling.
10.Preparation of berberine-naringin dual drug-loaded composite microspheres and evaluation of their antibacterial-osteogenic properties.
Wei XIONG ; Lingmei YUAN ; Liangxia WANG ; Guowen QIAN ; Chaoyi LIANG ; Bin PAN ; Ling GUO ; Wenqiang WEI ; Xunxiang QIU ; Wenfang DENG ; Zhikui ZENG
Chinese Journal of Reparative and Reconstructive Surgery 2023;37(12):1505-1513
OBJECTIVE:
To develop a drug-loaded composite microsphere that can simultaneously release the berberine (BBR) and naringin (NG) to repair infectious bone defects.
METHODS:
The NG was loaded on mesoporous microspheres (MBG) to obtain the drug-loaded microspheres (NG-MBG). Then the dual drug-loaded compound microspheres (NG-MBG@PDA-BBR) were obtained by wrapping NG-MBG with polydopamine (PDA) and modifying the coated PDA with BBR. The composite microspheres were characterized by scanning electron microscopy, X-ray diffraction, specific surface area and pore volume analyzer, and Fourier transform infrared spectroscopy; the drug loading rate and release of NG and BBR were measured; the colony number was counted and the bacterial inhibition rate was calculated after co-culture with Staphylococcus aureus and Escherichia coli for 12 hours to observe the antibacterial effect; the biocompatibility was evaluated by live/dead cell fluorescence staining and cell counting kit 8 assay after co-culture with rat's BMSCs for 24 and 72 hours, respectively, and the osteogenic property was evaluated by alkaline phosphatase (ALP) staining and alizarin red staining after 7 and 14 days, respectively.
RESULTS:
NG-MBG@PDA-BBR and three control microspheres (MBG, MBG@PDA, and NG-MBG@PDA) were successfully constructed. Scanning electron microscopy showed that NG-MBG@PDA-BBR had a rough lamellar structure, while MBG had a smooth surface, and MBG@PDA and NG-MBG@PDA had a wrapped agglomeration structure. Specific surface area analysis showed that MBG had a mesoporous structure and had drug-loading potential. Low angle X-ray diffraction showed that NG was successfully loaded on MBG. The X-ray diffraction pattern contrast showed that all groups of microspheres were amorphous. Fourier transform infrared spectroscopy showed that NG and BBR peaks existed in NG-MBG@PDA-BBR. NG-MBG@PDA-BBR had good sustained drug release ability, and NG and BBR had early burst release and late sustained release. NG-MBG@PDA-BBR could inhibit the growth of Staphylococcus aureus and Escherichia coli, and the antibacterial ability was significantly higher than that of MBG, MBG@PDA, and NG-MBG@PDA ( P<0.05). But there was a significant difference in biocompatibility at 72 hours among microspheres ( P<0.05). ALP and alizarin red staining showed that the ALP positive area and the number of calcium nodules in NG-MBG@PDA-BBR were significantly higher than those of MBG and NG-MBG ( P<0.05), and there was no significant difference between NG-MBG@PDA and NG-MBG@PDA ( P>0.05).
CONCLUSION
NG-MBG@PDA-BBR have sustained release effects on NG and BBR, indicating that it has ideal dual performance of osteogenesis and antibacterial property.
Rats
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Animals
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Osteogenesis
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Delayed-Action Preparations/pharmacology*
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Microspheres
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Berberine/pharmacology*
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Anti-Bacterial Agents/pharmacology*
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Escherichia coli