Rasfonin inhibits proliferation and migration of osteosarcoma 143B cells / 北京大学学报(医学版)

OBJECTIVE@#To investigate the effects of rasfonin, a fungal secondary metabolite, on the proliferation and migration of osteosarcoma 143B cells.@*METHODS@#3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay was performed to examine 143B cell viability following treatment of rasfonin. Using dimethyl sulfoxide (DMSO) group as control, cell viability was detected when 143B cells were treated with rasfonin (3 μmol/L and 6 μmol/L) for 12 or 24 hours. The effect of rasfonin on colony forming ability was detected by clone formation assay. 143B cells treated with DMSO or rasfonin (3 μmol/L) for one week, and the number of clones formed in the two groups was counted. Wound healing and transwell assay were employed to analyze cell invasion and migration upon rasfonin challenge. The DMSO group was used as control while rasfonin (3 μmol/L) was used for 24 hours. The wound healing rate and the number of invasive cells were compared between the two groups. The intracellular autophagosomes were monitored by transmission electron microscopy when 143B cells were treated with DMSO or rasfonin (3 μmol/L) for 4 hours. The expression of p62, microtubule-associated protein 1 light chain 3 fusion protein (LC3) and poly (ADP-ribose) polymerase-1 (PARP-1) in response to rasfonin were detected by immunoblotting assay.@*RESULTS@#Rasfonin reduced the viability of 143B cells in a dose-dependent manner (12 h: F=31.36, P<0.01; 24 h: F=67.07, P<0.01). Rasfonin (3 μmol/L) completely inhibited the clonal formation of 143B cells (P<0.01). The wound healing result revealed that rasfonin significantly decreased migratory ability of 143B cells (33.91%±0.83% vs. 65.11%±0.94%, P<0.01), whereas its treatment significantly reduced the number of 143B cells penetrating through Matrigel-containing basement membrane (21.33±1.45 vs. 49.33±2.40, P<0.01). Compared with the control group, rasfonin markedly increased the number of autophagic vacuoles. The immunoblotting results revealed that rasfonin increased LC3-II accumulation and decreased p62 levels. Choloroquine (CQ), an often used autophagic inhibitor, further accumulated rasfonin-induced LC3-II. In addition, rasfonin appeared to cause the cleavage of PARP-1.@*CONCLUSION@#Rasfonin induced autophagy and activated caspase-dependent apoptosis in 143B cells concurring with suppressing the proliferation and migration of the cells; these results provide an experimental basis for rasfonin as a potential therapeutic agent for osteosarcoma.

Surgical classification and therapeutic strategy for metastases of proximal femur / 中华外科杂志

<p><b>OBJECTIVE</b>To establish a surgical classification system for metastases of proximal femur and discuss the therapeutic strategy with retrospective analysis and literature review.</p><p><b>METHODS</b>The data of 99 patients who underwent a total of 102 operations for femoral metastatic lesions from January 2003 to December 2011 was analyzed. There were 50 males and 49 females, and the median age was 56 years (range 15-87 years). The most common diagnosis was lung cancer (30 cases), followed by breast cancer (17 cases). All femoral lesions were divided into 4 types (I-IV) with different anatomic site and biomechanic characteristic. The patients with various surgical reconstruction mode and postoperative follow-up data were recorded.</p><p><b>RESULT</b>There were 65 side who received widely or marginal resection and 37 side who received intralesional resection. The patients were operated with bipolar hip prosthesis (n = 3), ordinary total hip replacement (THR) (n = 10), bipolar tumor prosthesis (n = 48), THR with tumor prosthesis (n = 8), intramedullary nailing (n = 21), and plate/screw (n = 12). The estimated survival for the 99 patients was 10.3 months. Type I, II, III and IV patients with postoperative American Society of bone and soft tissue tumors-93 rating were 86.5%, 77.3%, 81.3% and 69.1%. Patients with type IV were worse compared with the other 3 groups (t = 4.763, P = 0.031). The 10 operations were followed by complications of any kind. Complication rate of patients with type IV were 3/12, and it was significantly higher than the other 3 groups of patients (χ(2) = 4.018, P = 0.045).</p><p><b>CONCLUSIONS</b>The classifications and corresponsive surgical methods for upper femur metastases had some superiority in hinting prognosis and guiding treatment.</p>

Evaluation of prognostic factors for synovial sarcoma / 中华外科杂志

<p><b>OBJECTIVE</b>To determine the independent prognostic factors of primary synovial sarcoma.</p><p><b>METHODS</b>The clinical data of 52 patients followed up from 66 patients with synovial sarcoma treated between September 1997 and September 2008 was analyzed retrospectively. There were 28 male and 24 female patients aged from 11 to 71 years old. Three and five-year overall survival (OS), recurrence rate and 9 prognostic factors were analyzed in this study. Univariate and multivariate analysis were performed to determine the prognostic factors of OS.</p><p><b>RESULTS</b>Fifty-two patients were followed up with the follow-up time ranged from 6 to 88 months (median 32 months). The 3-, 5-year overall survival rate and local recurrence rate were 52.8%, 30.3% and 32.7% respectively. Univariate showed tumor size < 5 cm, tumor located at extremities, adequate surgical margin and radical resection combined with radiotherapy had better survival rate (P < 0.05). Multivariate analysis demonstrated that tumor size, primary site and adequate surgical margin were independent prognostic factors for OS. Patients received radical resection combined with radiotherapy have longer median relapse time (25 months) compared with marginal resection combined with radiotherapy (18 months) and single radical resection (12 months). Thirty-five (67%) patients were treated with chemotherapy and seventeen (33%) patients received no chemotherapy for the primary tumor. Treatment with chemotherapy was not associated with an improved OS (P = 0.52).</p><p><b>CONCLUSIONS</b>The independent prognostic factors of synovial sarcoma are tumor size, primary site and adequate surgical margin. Doxorubicin and ifosfamide based chemotherapy was not associated with an improved OS in patients with synovial sarcoma. Radical resection combined with radiotherapy can best control local condition.</p>

The survival and functional outcome of primary bone sarcomas in distal lower extremity / 中华外科杂志

<p><b>OBJECTIVE</b>To analyze the oncological and functional outcome of limb salvage in this location.</p><p><b>METHODS</b>From November 2003 to January 2010, 20 patients with primary malignant bone tumors of the distal lower extremity were treated. There were 15 male and 5 female, the mean age was 20 years. Among 14 patients with malignant distal tibial sarcoma, 11 patients had ankle arthrodesis reconstructed by using allograft (7 patients) or autografts (4 patients), the other 3 patients underwent below-knee amputation. Three patients with osteosarcoma of distal fibula reconstructed with ipsilateral fibular head, 3 patients with calcaneus osteosarcoma underwent total calcanectomy and reconstructed with fibular segment and iliac crest. The mean follow-up was 36.4 months.</p><p><b>RESULTS</b>Five of 7 (71.4%) patients with allograft reconstruction were associated with delayed wound healing, however, only 1 of 10 patients with autograft had this problem (P = 0.036). One local recurrence was observed, 2 osteosarcoma patients died of disseminated disease. The estimated 2-year and 5-year overall survival for the patients with malignant tibial sarcomas were 92.9% and 79.6% respectively, for the patients with distal tibial high-grade osteosarcoma were 87.5% and 70.0% respectively. The mean functional MSTS score was 82% for limb salvage patients.</p><p><b>CONCLUSIONS</b>The survival of patients with primary malignant bone tumor of distal lower extremity seems to be better than that of other sites. Limb salvage can provide satisfactory local control and functional results.</p>

The surgical management of sacral chordoma / 中华外科杂志

<p><b>OBJECTIVE</b>To analyze the surgical treatment results and experience of sacral chordoma.</p><p><b>METHODS</b>The data of 51 cases of sacral chordoma surgically treated from July 1997 to July 2007 was retrospectively studied. The age of patients ranged from 21 to 75 years (mean 57 years), including 32 males and 19 females. Forty patients had the first surgery, while other 11 patients were referred to our hospital because of local recurrence from other hospital. Wide resection for all 17 S(3-5) tumors, and wide resection plus piece-meal excision for 34 tumors which involved S(3) above. Reconstruction was performed using pedicle screw and rod device to achieve the continuity between the lumbar spine and the pelvis. The oncologic and functional outcomes of 51 patients were reviewed.</p><p><b>RESULTS</b>After a mean duration of follow-up of 3.5 years (range from 15 to 108 months), 5 of 51 patients died of disease. Seventeen of 40 (42.5%) patients who underwent first surgery recurred during follow-up, 18 of 28 patients (64.3%) got re-relapse after second or third surgeries. Postoperative wound complications were as high as 31.6%.</p><p><b>CONCLUSIONS</b>Chordoma is a biologically aggressive low-grade malignant tumor. Wide resection is a prerequisite for curative treatment of sacrococcygeal chordoma, intralesional curettage causes the risk of high local recurrence for which curative resection in a second or third procedure is more difficult to achieve. In order to preserve near normal bowel and bladder function for the tumor which involves S(3) above, wide en-bloc resection plus piece-meal excision in the cephalad is performed.</p>

The clinical outcome of proximal fibular osteosarcoma with en-bloc resection / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the local recurrence and 5-year survival of proximal fibular osteosarcoma.</p><p><b>METHODS</b>From October 1997 to July 2005, 12 patients with proximal fibular osteosarcoma were treated. There were 9 males and 3 females. The mean age at diagnosis was 16 (9-23) years old. Histopathological diagnosis were obtained by trut-cut biopsy, Enneking surgical stages of 12 lesions were as follows: 11 grade II B and 1 grade III. Induction chemotherapy was applied to all patients except one who left the hospital after the biopsy. Of 11 patients, 8 were performed Malawer type I resection, and 3 type II. All patients continued to get postoperative chemotherapy.</p><p><b>RESULTS</b>Regular follow-up was applied. Only 1 patient was found local recurrence one year after operation and received re-resection, the others did not. Four patients died of lung metastases, including the one who did not get treated, one stage III and two II B patients. The range of follow up was 6 to 117 months. The evaluated 5 year disease-free survival of 11 patients who got treated was 72.7% by using Kaplan Meier survival analysis.</p><p><b>CONCLUSIONS</b>The local recurrence is low, and 5 year disease-free survival is acceptable, in accordance with present point that marginal resection may not impact survival for fibular osteosarcoma. No knee instability is found in this group after great care is taken for proper reconstruction of lateral collateral ligament and reinsertion of biceps femoris tendon on the lateral condyle of tibia.</p>

Resection and reconstruction of upper thoracic tumor by high transthoracic approach / 中华外科杂志

<p><b>OBJECTIVES</b>To define the role of high transthoracic approach in the treatment of cervicothoracic and high thoracic tumor, and analyze the problem encountered during tumor resection and reconstruction of this technique and oncological results of patients who received this type of surgery.</p><p><b>METHODS</b>Twenty-one patients with cervicothoracic and high thoracic tumor (T(1 - 4)) were treated with high transthoracic approach. This series included metastatic tumor 11 patients, eosinophilic granuloma of bone 2 patients, osteosarcoma 1 patient, Ewing's sarcoma 2 patients, chondrosarcoma 2 patients, giant cell tumor 2 patients, lymphoma 1 patient. High transthoracic approach was applied to these patients for tumor resection and spinal cord decompression. Reconstruction method included artificial vertebrae implantation or bone graft implantation combined with anterior internal fixation.</p><p><b>RESULTS</b>Chest-back pain of all patients relieved significantly after operation. Paraplegia of 3 patients was improved from grade A to grade D according to Frankel grading system, the other 2 patients recovered completely. Pulmonary infection and pulmonary atelectasis occurred in 2 patients; cerebrospinal fluid leakage happened in 1 patient; thoracic aorta rupture happened in 1 patient. The follow-up period was 11 - 58 months, 9 patients died, including 7 patients with metastatic cancer, 1 patient with Ewing's sarcoma, 1 patient with osteosarcoma.</p><p><b>CONCLUSIONS</b>High transthoracic approach is a satisfactory method in dealing with the lesion of cervicothoracic and high thoracic vertebrae, especially with the lesion involving the vertebrae and single vertebral arch. The thoracic canal can be decompressed effectively by this approach.</p>

Clinical study of solitary bone plasmacytoma / 中华外科杂志

<p><b>OBJECTIVE</b>To study the clinical characteristics and the prognosis of solitary bone plasmacytoma (SBP).</p><p><b>METHODS</b>From June 1997 to June 2002, ten SBP patients were treated in our department. Two lesions were in sacrum, two in pelvis, the other six lesions were in proximal femur, femoral diaphyseal, scapula, thoracic vertebra, proximal humus, and rib respectively. The preoperative laboratory tests were normal. Operation was performed on all patients. The pathologic diagnose was plasmacytoma and then they underwent further laboratory examination, urine Bence-Jone protein is positive in 3 patients, serous IgG value was higher than normal in 2 patients, abnormal M protein was found in electrophoresis in 2 patients. All patients received radiotherapy postoperatively.</p><p><b>RESULTS</b>Four patients were excluded, whose follow-up were lessen than ten months, the other six patients's average follow-up is 28.2 months (from 18 to 48 months), one patient who developed multiple myeloma (MM) six months postoperatively received chemotherapy using M2 protocol and died 21 months after operation. The other five patients had disease-free survive and remain solitary bone lesion after the treatment of surgery and radiology.</p><p><b>CONCLUSION</b>Compared with MM, SBP patients are younger, the therapeutic results and prognosis are better. The main prognostic factors include age, the size of lesion, the axial bone lesion, persistence of myeloma protein after radiotherapy, early diagnosis and treatment, and so on.</p>