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Background and Purpose: Telangiectatic osteosarcoma (TOS), a rare variant of osteosarcoma, may be easily misdiagnosed as aneurysmal bone cyst (ABC). The aims of this study were to investigate the diagnostic and prognostic factors of TOS by reviewing our experience with TOS and to develop a diagnostic model that may distinguish TOS from ABC., Materials and Methods: We identified 51 cases of TOS treated at the First Affiliated Hospital of Sun Yat-Sen University from March 2001 to January 2016 and reviewed their records, imaging information and pathological studies. A diagnostic model was developed to differentiate TOS and ABC by Bayes discriminant analysis and was evaluated. The log-rank test was used to analyze the prognostic factors of TOS and to compare the outcome differences between TOS and other high-grade osteosarcoma subtypes., Results: The multi-disciplinary diagnostic method employed that combined clinical, imaging, and pathological studies enhanced the diagnostic accuracy. Age 18 years or younger and pathologic fracture were more common among the TOS patients than among the ABC patients (P = .004 and .005, respectively). The average white blood cell (WBC), platelet, lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) values of the TOS patients were higher than those of the ABC patients ( P = .002, .003, .007, and .007, respectively). Our diagnostic model, including the aforementioned factors, accurately predicted 62% and 78% of the TOS patients in the training and validation sets, respectively. The 5-year estimates of event-free survival and overall survival of the TOS patients were 52.5 ± 9.4% and 54.9 ± 8.8%, respectively, which were similar to those of patients with other osteosarcoma subtypes ( P = .950 and .615, respectively). Tumor volume and the LDH level were predictive prognostic factors ( P = .040 and .044) but not the presence of pathologic fracture or misdiagnosis ( P = .424 and .632, all respectively)., Conclusions: The multi-disciplinary diagnostic method and diagnostic model based on predictive factors, i.e. , age, the presence of pathologic fracture, and platelet, LDH, ALP and WBC levels, aided the differentiation of TOS and ABC. Smaller tumors and normal LDH levels were associated with better outcomes.

Ampelopsin (AMP), a plant flavonoid, has been reported to inhibit cell growth and/or induce apoptosis in various types of tumor. The aim of the present study was to assess the apoptosis-inducing activity of AMP in A549 human lung adenocarcinoma epithelial cells and the associated underlying mechanism. A549 cells were incubated with different concentrations of AMP in culture medium. Cell growth and apoptosis were evaluated by MTT assay and Annexin V/propidium iodide double staining and flow cytometry, respectively. In addition, western blotting and reverse transcription quantitative polymerase chain reaction analysis were used to examine the time-dependent changes in protein expression. Certain changes in apoptotic protein expression were detected following exposure to AMP, including X-linked inhibitor of apoptosis protein release, reduced B-cell lymphoma 2, myeloid cell leukemia 1 and survivin expression levels, increased Bcl-2-associated X protein expression levels and cleaved-poly ADP ribose polymerase expression. The results revealed that AMP was a potent inhibitor of A549 cell proliferation. The c-Myc/S-phase kinase-associated protein 2 (Skp2) and histone deacetylase (HDAC)1/2 pathways were found to exert an important role in AMP-induced A549 cell apoptosis, as increased levels of c-Myc mRNA and reduced levels of c-Myc/Skp2 and HDAC1 and 2 proteins following AMP treatment were observed. The levels of F-box and WD repeat-containing protein 7α (Fbw7α), Fbw7β, Fbw7γ, phosphorylated-(p-)c-Myc (Thr58) and glycogen synthase kinase 3β (GSK3β) proteins involved in c-Myc ubiquitin-dependent degradation were also analyzed. Following exposure to AMP, the expression levels of Fbw7α, Fbw7γ and GSK3β were reduced and p-c-Myc (Thr58) expression levels were increased. The results suggest that AMP exerts an anticancer effect, which is associated with the degradation of c-Myc, Skp2 and HDAC1 and 2. The ability of AMP to induce apoptosis independently of Fbwα and Fbw7γ suggests a possible use in drug-resistant cancer associated with Fbw7 deficiency. Understanding the exact underlying mechanism requires further investigation of the association between c-Myc and Fbw7α/γ reversal, and analysis of whether Thr58 phosphorylation of c-Myc is dependent on GSK3β.

Objective: To study the apoptosis inducing effects of bufalin on various human osteosarcoma cells and the concerning molecular mechanisms., Method: MTT assay was used to detect the growth inhibition rates of osteosarcoma cells U-20S, U-20S/MTX300, SaOS-2, IOR/OS9 treated with bufalin in different concentrations and times. The apoptosis of cells was observed flow cytometry 48 h following bufalin treatment. The proteomic techniques were used to separate and compare the treated and control groups 48 h after bufalin-incubation. Then, the proteomic results were validated by western blot., Result: Bufalin inhibited the growth of human osteosarcoma cells U20S, U20S/MTX300 (methotrexate resistant cells), SAOS2, IOR/OS9 in a dose- and time-dependent manner. The 72 h IC50 were (37.43 +/- 4.1), (32.24 +/- 5.3) nmol x L(-1) in U20S,U20S/MTX300 cells,respectivly. Flow cytometry showed that the apoptosis cells were increased following bufalin treatment. The protein expression profile showed 24 differentiated expression proteins. Among these proteins, the level of an anti-apoptotic protein, heat shock protein 27 (Hsp27) decreased significantly and the result was then validated by western blot. Ectopic expression of Hsp27 could reduce the bufalin-induced apoptosis remarkably in U20S and U20S/MTX300 cells., Conclusion: Bufalin could inhibit the cell growth and induce apoptosis on human osteosarcoma cells. The effect of bufalin may be related to the joint intervention with multiple protein targets. Among them, downregulation of Hsp27 plays a critical role in the bufalin-induced apoptosis in human osteosarcoma cells.

Objective: With the extremity soft tissue sarcoma close to neurovascular bundle, combined en bloc resection and brachytherapy or simple en bloc resection were performed to evaluate the treatment outcome of the combined en bloc resection and brachytherapy., Methods: Retrospectively investigation was performed for the extremity soft tissue sarcoma close to neurovascular bundle between 2000 and 2009. Inclusion criteria were primary extremity soft tissue sarcoma, MRI showed that the reaction zone involved the main neurovascular bundle, and the reaction zone closed less than 1 cm to the main neurovascular bundle. 86 cases were included in the study. There were 41 men and 45 women. The average age was 38.5 years old (Range from 15 to 73). There were malignant fibrous histiocytoma, synovial sarcoma, fibrosarcoma, liposarcoma, clear cell sarcoma, epithelioid sarcoma, leiomyosarcoma, rhabdomyosarcoma and vascular sarcoma etc. The stage were IA (8), IIA (12), IIB (10), IIC (7), III (43) and IV (6)., Results: During an average follow-up of 53 months (range 24 - 102 months), the distant metastasis rate 32.56% (28/86) and the lymph node metastasis rate was 6.98% (6/86). The local recurrence rates was 13.95% (12/86). In the group of combined en bloc resection and brachytherapy with 38 cases, the local recurrence rates was 5.26% (2/38). Four cases had wound infection and six cases had wound delay healing. The MSTS functional score was 21.11 ± 1.79. In the group of simple en bloc resection with 48 cases, the local recurrence rates was 20.83% (10/48). One case had wound infection and four cases had wound delay healing. The MSTS functional score was 84.23% (26.11 ± 1.79). The local recurrence rates was significant different between., Conclusion: With the extremity soft tissue sarcoma close to neurovascular bundle, combined en bloc resection and brachytherapy could decrease the local recurrence rate.

Objective: To study the growth inhibition and apoptosis induction effects of bufalin on human osteosarcoma cell lines in vitro., Methods: U-2OS and U-2OS/methotrexate (MTX) 300-resistant cell lines were treated with bufalin. Cell viability was assessed by MTT assay. Cell-cycle status, apoptosis-inducing effects, and the expression of apoptosis-related proteins were evaluated by flow cytometry, fluorescent staining, DNA fragmentation assay, and Western blotting., Results: Bufalin inhibited cell growth in both U-2OS and U-2OS/MTX300 cells. The IC(50) values of bufalin for U-2OS and U-2OS/MTX300 cells were (8.49 ± 2.1) ng/ml and (10.19 ± 1.7) ng/ml, respectively. The induction of G(2)/M cell-cycle arrest was also seen in the bufalin-treated cells. The bufalin-induced apoptosis was confirmed by increased expression of tumor suppressor protein p53, bax and decreased expression of bcl-2., Conclusion: Bufalin inhibits the growth of and induces apoptosis in both MTX-sensitive and MTX-resistant human osteosarcoma U-2OS cell lines. The apoptosis-inducing effect of bufalin is not influenced by the presence of high levels of DHFR.

Objective: To detect differentially expressed proteins in serum of patient with osteosarcoma., Methods: 8 serum protein samples were recruited (4 cases of osteosarcoma and 4 cases of normal adults), cross-labeled with variant CyDye, followed by two-dimensional differential in-gel electrophoresis (2-D DIGE), image analysis, and identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS)., Results: 24 protein spot-features were significantly increased, and 34 were significantly decreased in the serum from patients with osteosarcoma relative to the controls. The mass spectrometry analysis revealed 18 unique proteins that were increased, and 25 unique proteins decreased in the serum of patients with osteosarcoma. Gelsolin was down-regulated in osteosarcoma, and Western blotting also confirmed a decreased level of gelsolin in the serum of patients with osteosarcoma., Conclusion: Our results indicate that gelsolin may have great potential as a biomarker of osteosarcoma and as a potential target for therapy. These preliminary data suggest that incorporation of more samples and new datasets will permit the identification of serum biomarkers for osteosarcoma.

We performed 2-D DIGE on proteins prepared from serum obtained from patients with osteosarcoma (OS) and controls, to identify differentially expressed proteins that might serve as serum biomarkers for OS prognosis. Proteins found to be differentially expressed were identified by MALDI-TOF mass spectrometric analysis, coupled with database interrogation. We compared serum samples from four individuals with OS to four age- and sex-matched healthy controls. We identified 24 protein spot-features that were significantly increased, and 34 that were significantly decreased in serum from patients with OS relative to the controls. The MS analysis revealed 18 unique proteins that were increased, and 25 unique proteins that were decreased in OS serum samples. Western blot and ELISA analysis confirmed increased levels of amyloid-related serum protein (SAA) in the OS serum samples. The increased expression levels of SAA were decreased after using MTX and cisplatin combination chemotherapy, and were further decreased after operation. Moreover, increased expression levels of sera SAA were seen in the relapsed patients. Our results suggested that the determination of serum SAA in OS patients might be utilized as a marker for relapse and in evaluation of the efficacy of therapy., (Copyright © 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To test 32 traditional Chinese medicinal herbs with effects against osteosarcoma in vitro., Methods: U(2)OS human osteosarcoma cell line was treated with the extracts of the Chinese herbs at various concentrations. The changes in cell proliferation in response to the treatment were examined by MTT assay, and the effects of these extracts against human osteosarcoma growth were compared. Morphological observation, flow cytometry and Annexin V were employed to detect the cell apoptosis after the treatments., Results: According to the results of MTT assay, several of the 32 Chinese herbs, especially Venenum Bufonis and oxgall powder, were identified to produce growth inhibition against U(2)OS cells. Further study of the aqueous extracts of Venenum Bufonis and oxgall powder demonstrated their effects in inducing U(2)OS cell apoptosis, and Venenum Bufonis showed the strongest effect. In spite of the obvious growth inhibitory effect of oxgall powder, its extract induced cell apoptosis only at high concentrations., Conclusion: Several of the traditional Chinese herbs, especially Venenum Bufonis and oxgall powder, may inhibit the growth of U(2)OS cell line, and the results of this study pave the way for further identification of the effective components in the herbs that inhibit osteosarcoma growth both in vivo and in vitro.

Objective: To analyze the clinical factors affecting the recurrence of giant cell tumors (GCT) of bone., Methods: The complete data of 146 cases with GCT were reviewed. Thirteen clinical factors were analyzed by chi(2) analysis. And the related Campanacci's grade system and Jaffe's grade system was analyzed by Crosstabs analysis. Multipal factors were analyzed by Logistic regression analysis., Results: Nineteen of 146 cases recurred, and recurrence rate was 13.0%. Recurrence rates of curettage and enblock resection groups were 18.8% and 6.3% respectively. And recurrence rates of curettage with or without of extensive procedure were 12.9% and 38.9%. Five cases had lung metastasis, and two cases presented with malignant transformation. The metastasis rate and the rate of malignant transformation were 3.4% and 1.4% respectively. The two factors of surgery method and burst out of bone-envelope appearance were related with the recurrence. Moreover, Logistic regression revealed that the surgery method significantly affected the recurrence. And Campanacci's grade system and Jaffe's grade system were not related to each other., Conclusions: Surgery method is the main factor affected the recurrence of GCT, and Campanacci's grade system or Jaffe's grade system has no prognostic value.