Synthesis and Anti-Breast Cancer Evaluation of Novel N-(Guanidinyl)benzenesulfonamides

Scientific and Technologial Innovation Programs of the Nanjing military region, China [10MA077]A series of 4-(substituted)-N-(guanidinyl)benzenesulfonamides bearing biologically active pyrazole, pyrimidine and pyridine moieties were prepared and evaluated for their anticancer activity against human tumor breast cell line (MCF7). These sulfonamides showed promising activity with IC50 values ranging from 49.5 to 70.2 mu M. The structure-activity relationship of the synthesized compounds was studied. Interestingly, it was found that the most potent compounds in this study were the corresponding 2-cyanoacrylate 3, 3-oxobutanoate 4, pyrazole 6, pyridine 9 and pyrazole 13. Compounds 7 and 8 are nearly as active as Doxorubicin as reference drug with (IC50 values = 70.2, 68.1 mu M), while compounds 5, 10 and 11 exhibited a moderate activity

Voltage-Gated Potassium Channel Kv13 Is Highly Expressed in Human Osteosarcoma and Promotes Osteosarcoma Growth

Scientific and Technologial Innovation Programs of of Nanjing Military Region, China [10MA077]Deregulation of voltage-gated potassium channel subunit Kv1.3 has been reported in many tumors. Kv1.3 promotes tumorigenesis by enhancing cell proliferation while suppressing apoptosis. However, the expression and function of Kv1.3 in osteosarcoma are unknown. In the present study, we detected the expression of Kv1.3 in human osteosarcoma cells and tissues by RT-PCR, Western blot and immunohistochemistry. We further examined cell proliferation and apoptosis in osteosarcoma MG-63 cells and xenografts following knockdown of Kv1.3 by short hairpin RNA (shRNA). We found that Kv1.3 was upregulated in human osteosarcoma. Knockdown of Kv1.3 significantly suppressed cell proliferation and increased apoptosis as demonstrated by enhanced cleavage of poly (ADP-ribose) polymerase (PARP) and the activation of Caspase-3/7. Furthermore, adenovirus delivered shRNA targeting Kv1.3 significantly inhibited the growth of MG-63 xenografts. Taken together, our results suggest that Kv1.3 is a novel molecular target for osterosarcoma therapy

Experimental Studies on Reconstructing Compression Side Femoral Cortical Bone Defect with Allogeneic Cortical Bone Plate

目的探讨同种异体皮质骨板重建压力侧骨皮质缺损的可行性及效果。方法24只成年山羊,制作压力侧骨皮质缺损动物模型。随机分两组,实验组12只:行异体骨板、钢板固定结合植骨;对照组12只:仅行钢板固定结合植骨。于术后4、8、12周进行影像学观察,生物力学测试和组织学检查。结果术后实验组内固定位置均良好,对照组4例发生螺钉松动、钢板断裂等内固定失效现象。12周时实验组髓腔再通,异体皮质骨与宿主骨融合;对照组仍可见不均匀骨痂影。各时间点两组标本的抗扭转、抗压缩刚度比较具有非常显著性差异(P<0.01)。组织学检查按Lane等评分标准评分,有非常显著性差异(P<0.01)。结论同种异体皮质骨板能够结构性重建骨皮质缺损区,恢复其承载功能,有效防止内固定失败,促进骨折愈合。Objective To explore the feasibility and effect of reconstructing compression side femoral cortical bone defect with allegeneic cortical bone plate.Methods 24 adult goats were divided into two groups randomly,12 animals respectively in experiment group and control group.At 4、8、12 weeks postoperatively,all animals were made X-ray exam,and then sacrificed.The left sides of femur were taken as specimens for biomechanical test and histopathological examination.Results Loosening or breakage of plates or screws were found for four animals in the control group,while the instruments were in the right site in experiment group.12 weeks the medullary cavity appeared again,the allogeneic cortical bone linked with host bone,fracture area repaired completely.While irregulary bone callus was existing in control group.Betweeen experiment group and control group,distinct difference(P<0.01)were found in hardscale of vertical compression,torsion at post-operatively immediately 4,8 and 12 weeks.According to Lane standard,there were distinct difference in the histopathological examination(P<0.01).Conclusion Allogeneic cortical bone plates associated with steel plate can rebuild the cortical bone defect structurally and recovery the function of load bearing,and it is a valid means to accelerate bone union and prevent the failure of fixations.南京军区“十一五”计划课题资助项目(06MA97

Modified technique using allograft-prosthetic composite in the distal femur after bone tumor resection

Background: The purpose of this retrospective study was to analyze the results of treatment of bone tumor resection of the distal femur with the modified technique of allograft-prosthetic composite. Methods: Twelve patients with distal femoral bone tumors were treated with deep-frozen cortical allograft struts and allograft-prosthesis composites. There were five males and seven females with a median age of 29.5 y. The minimum follow-up time was 12 mo (median, 45.7 mo; range, 12-81 mo). Diagnoses included osteosarcoma in five patients, chondrosarcoma in three patients, giant cell tumors in three patients, and malignant fibrous histiocytoma in one patient. Five osteosarcoma patients were treated with adjuvant chemotherapy. Results: At the latest follow-up examination, 11 patients were alive with no evidence of disease, and the limb was preserved in nine patients. One patient died of pulmonary metastases with no evidence of local recurrence. Seven healed without complications. A surgical procedure was performed in four patients because of complications, which included a fracture (one patient), deep infection (one patient), instability (one patient), and local recurrence (one patient). Conclusion: The modified technique of allograft-prosthetic composite is an effective treatment for bone tumor resection of the distal femur. This technique has many advantages, including augmentation of the bone stock, minimizing the risk of allograft fracture and nonunion, and decreasing the need for revision operations. Crown Copyright (C) 2013 Published by Elsevier Inc. All rights reserved

Artificial Disk Replacement Combined With Midlevel ACDF Versus Multilevel Fusion for Cervical Disk Disease Involving 3 Levels

The optimal surgical approach for cervical disk disease remains a matter of debate, especially for multilevel disease. The purpose of this study was to compare the results of 2 surgical strategies for cervical disk disease involving 3 levels: hybrid constructs, artificial disk replacement combined with midlevel anterior cervical diskectomy and fusion (ACDF), and 3-level ACDF. The authors prospectively compared patients who had cervical disk disease involving 3 levels that was treated with hybrid constructs or with 3-level ACDF. Patients were asked to use the Neck Disability Index (NDI) to grade their pain intensity preoperatively and at routine postoperative intervals of 1, 3, 6, 12, and 24 months. Dynamic flexion and extension lateral cervical radiographs were obtained while in the standing position preoperatively and at the postoperative intervals. The angular range of motion for C2-C7 and the adjacent segments was measured using the Cobb method. Twenty-four patients were treated, 12 with hybrid constructs and 12 with 3-level ACDF. Both groups had significant postoperative improvement in NDI scores and neck pain (P.05). The hybrid constructs group showed faster recovery of C2-C7 range of motion. Mean C2-C7 range of motion of the hybrid constructs group recovered to that of the preoperative value, but that of the 3-level ACDF group did not (P<.05). Range of motion of the superior and inferior adjacent segments showed significant differences between the 2 groups at 12 and 24 months postoperatively (P<.05). These findings suggest that the hybrid constructs is a safe and effective alternative for cervical disk disease involving 3 levels. The definite stabilization and maintained range of motion can be achieved right away, which can ensure a good preliminary clinical outcome

Anterior Versus Posterior Approach for Four-level Cervical Spondylotic Myelopathy

The purpose of this study was to compare the results of 2 surgical strategies for 4-level cervical spondylotic myelopathy: a hybrid procedure using anterior cervical diskectomy and fusion (ACDF) combined with segmental corpectomy versus posterior laminectomy and fixation. Between 2002 and 2010, fifty-one patients with consecutive 4-level cervical spondylotic myelopathy were treated surgically, with 27 patients undergoing the hybrid procedure and 24 undergoing posterior laminectomy and fixation. Radiologic data were compared between the 2 groups, including cervical curvature and cervical range of motion (ROM) in the sagittal plane. Pre- and postoperative neurological status was evaluated using the Japanese Orthopaedic Association (JOA) scoring system and the Nurick grading system. Mean ROM at last follow-up was not significantly different between the 2 groups (P>.05). In the hybrid group, mean JOA score and Nurick grade improved from 9.6+/-1.4 and 2.74+/-0.45 respectively, preoperatively, to 13.9+/-1.3 and 0.86+/-0.38 respectively, postoperatively. In the fixation group, mean JOA score and Nurick grade improved from 9.4+/-1.2 and 2.81+/-0.42 respectively, preoperatively, to 13.1+/-1.5 and 1.32+/-0.36 respectively, postoperatively. The JOA scores and Nurick grades at last follow-up were significantly different between the 2 groups (P.05); however, JOA scores and Nurick grades at last follow-up showed better improvement in the hybrid group than in the fixation group (P.05)

Biomechanical Study Comparing a New Combined Rod-plate System With Conventional Dual-rod and Plate Systems

Key Foundation of Nanjing Army [09Z020, 10Z022]Most anterior spinal instrumentation systems are designed as either a plate or dual-rod system and have corresponding limitations. Dual-rod designs may offer greater adjustability; however, this system also maintains a high profile and lacks a locking design. Plate systems are designed to be stiffer, but the fixed configuration is not adaptable to the variety of vertebral body shapes. The authors designed a new combined rod-plate system (D-rod) to overcome these limitations and compared its biomechanical performance with the conventional dual-rod and plate system. Eighteen pig spinal specimens were divided into 3 groups (6 per group). An L1 corpectomy was performed and fixed with the D-rod (group A; n=6), Z-plate (Sofamor Danek, Memphis, Tennessee) (group B; n=6), or Ventrofix (Synthes, Paoli, Pennsylvania) (group C; n=6) system. T13-L2 range of motion was measured with a 6 degrees of freedom (ie, flexion-extension, lateral bending, and axial rotation) spine simulator under pure moments of 6.0 Nm. The D-rod and Ventrofix specimens were significantly stiffer than the Z-plate specimens (P <.05) based on results obtained from lateral bending and flexion-extension tests. The D-rod and Z-plate specimens were significantly stiffer than the Ventrofix specimens (P <.05) in axial rotation. The D-rod combines the advantages of the plate and dual-rod systems, where the anterior rod exhibits the design of a low-profile locking plate, enhanced stability, and decreased interference of the surrounding vasculature. The posterior rods function in compression and distraction, and the dual-rod system offers greater adjustability and control over screw placement. The results indicate that it may provide adequate stability for anterior thoracolumbar reconstruction

Posteromedial Anatomical Plate for the Treatment of Distal Tibial Fractures With Anterior Soft Tissue Injury

Nanjing Military Region [07M068

Anterior Versus Posterior Approach for Four-level Cervical Spondylotic Myelopathy

The purpose of this study was to compare the results of 2 surgical strategies for 4-level cervical spondylotic myelopathy: a hybrid procedure using anterior cervical diskectomy and fusion (ACDF) combined with segmental corpectomy versus posterior laminectomy and fixation. Between 2002 and 2010, fifty-one patients with consecutive 4-level cervical spondylotic myelopathy were treated surgically, with 27 patients undergoing the hybrid procedure and 24 undergoing posterior laminectomy and fixation. Radiologic data were compared between the 2 groups, including cervical curvature and cervical range of motion (ROM) in the sagittal plane. Pre- and postoperative neurological status was evaluated using the Japanese Orthopaedic Association (JOA) scoring system and the Nurick grading system. Mean ROM at last follow-up was not significantly different between the 2 groups (P>.05). In the hybrid group, mean JOA score and Nurick grade improved from 9.6+/-1.4 and 2.74+/-0.45 respectively, preoperatively, to 13.9+/-1.3 and 0.86+/-0.38 respectively, postoperatively. In the fixation group, mean JOA score and Nurick grade improved from 9.4+/-1.2 and 2.81+/-0.42 respectively, preoperatively, to 13.1+/-1.5 and 1.32+/-0.36 respectively, postoperatively. The JOA scores and Nurick grades at last follow-up were significantly different between the 2 groups (P.05); however, JOA scores and Nurick grades at last follow-up showed better improvement in the hybrid group than in the fixation group (P.05)

A distal femoral supra-condylar plate: biomechanical comparison with condylar plate and first clinical application for treatment of supracondylar fracture

[09z020]An anatomical supra-condylar plate is designed and analysed by biomechanical testing. The biomechanical properties of the supra-condylar and condylar plate were compared in six matched pairs of cadaveric femurs. A transverse osteotomy gap was created to simulate an OTA/AO type A3 supracondylar fracture. The left and right specimens were fitted with supra-condylar and condylar plate, respectively. Nondestructive axial compression, three-point bending and torsion tests were performed, and the peak load of the bone-implant construction was measured. The fracture site suitable for supra-condylar plate application and its correlation with femoral length were calculated. The gender influence on it was also discussed. The difference of stiffness between the supra-condylar and condyle groups were not significant (P > 0.05) at 363.4 and 362.5 N/mm for compression, 229.5 and 237.6 N/mm in the sagittal plane and 195.5 and 188.4 N/mm in the coronal plane for three-point bending, and 7.5 and 7.9 Nm/deg for axial torsion, respectively. The peak load was 4438 +/- 136.15 N and 5215 +/- 174.33 N, respectively, for the two groups. The average extent of the fracture site suitable for the application of the supra-condylar plate was 70.86 +/- 4.61 mm. The femoral length and gender showed no influence on it. Despite the limited bone contact area provided by the supra-condylar plate, its construct stiffness is comparable to the condylar plate. The supra-condylar plate can be used to treat carefully-selected extra-articular supracondylar fractures