Huimin Tao

Multicentric Epithelioid Angiosarcoma of Bone

Bone epithelioid angiosarcoma is rare and generally shows positive immunostaining for epithelial markers. Multicentric bone epithelioid angiosarcoma is easily misdiagnosed as carcinoma, including metastatic carcinoma, multiple myeloma, and multiple lymphoma of bone. This article describes a case of multicentric bone epithelioid angiosarcoma. The patient was first misdiagnosed as having metastatic carcinoma. Examination showed osteolytic lesions in the bilateral heels and the lower left humerus. The diagnosis was confirmed postoperatively and corrected after immunohistochemical analysis of the biopsy. The immunohistochemical analysis revealed that the tumor mass was strongly positive for CD31, factor VIII, vimentin, and neuron-specific enolase. The patient refused chemotherapy and died of lung metastasis 4 months postoperatively.Most bone epithelioid angiosarcomas are immunopositive for epithelial markers (ie, keratin, cytokeratin, high-molecular-weight keratin, and epithelial membrane antigen), vascular endothelial markers (ie, CD31, CD34, and von Willebrand factor), and factor VIII-associated antigen. Bone epithelioid angiosarcoma shows a relatively high degree of malignancy. Patients often die of distant metastasis, including those found in the lung and lymph node tissue. A wide excision of epithelioid angiosarcoma should be performed during the operation of the primary tumor. A better understanding of the clinicopathologic features of this disease may help to clarify the confusion, provide better treatment, and improve the clinical prognosis.

A review and outlook in the treatment of osteosarcoma and other deep tumors with photodynamic therapy: from basic to deep

Photodynamic therapy, one of the most promising minimally invasive treatments, has received increasing focus in tumor therapy research, which has been widely applied in treating superficial tumors. Three basic factors - photosensitizer, the light source, and oxidative stress - are responsible for tumor cell cytotoxicity. However, due to insufficient luminous flux and peripheral tissue damage, the utilization of photodynamic therapy is facing a huge limitation in deep tumor therapy. Osteosarcoma is the typical deep tumor, which is the most commonly occurring malignancy in children and adolescents. Despite developments in surgery, high risks of the amputation still threatens the health of osteosarcoma patients. In this review, we summarize recent developments in the field of photodynamic therapy and specifically PDT research in OS treatment modalities. In addition, we also provide some novel suggestions, which could potentially be a breakthrough in PDT-induced OS therapies. PDT has the potential to become an effective therapy while the its limitations still present when applied on the treatment of OS or other types of deep tumors. Thus, more researches and studies in the field are required.

Escin induces caspase-dependent apoptosis and autophagy through the ROS/p38 MAPK signalling pathway in human osteosarcoma cells in vitro and in vivo

Osteosarcoma is one of the most malignant neoplasms in adolescents, and it generally develops multidrug resistance. Escin, a natural mixture of triterpene saponins isolated from Aesculus hippocastanum (horse chestnut), has demonstrated potent anti-tumour potential in vitro and in vivo. In the present study, we found that escin inhibited osteosarcoma proliferation in a dose- and time-dependent manner. Additionally, escin-induced apoptosis was evidenced by the increased expression of caspase-related proteins and the formation of apoptotic bodies. Escin also induced autophagy, with elevated LC3, ATG5, ATG12 and Beclin expression as well as autophagosome formation. Inhibition of escin-induced autophagy promoted apoptosis. Moreover, p38 mitogen-activated protein kinases (MAPKs) and reactive oxygen species (ROS) were activated by escin. A p38 MAPK inhibitor partially attenuated the autophagy and apoptosis triggered by escin, but a ROS scavenger showed a greater inhibitory effect. Finally, the therapeutic efficacy of escin against osteosarcoma was demonstrated in an orthotopic model. Overall, escin counteracted osteosarcoma by inducing autophagy and apoptosis via the activation of the ROS/p38 MAPK signalling pathway; these findings provide evidence for escin as a novel and potent therapeutic for the treatment of osteosarcoma.

Reconstruction of large tibial bone defects following osteosarcoma resection using bone transport distraction: A report of two cases

The clinical efficiency of bone transport distraction osteogenesis in the reconstruction of large tibial defects following resection of osteosarcoma remains unclear. The current study presents two cases of large tibial defects treated with bone transport distraction using an Orthofix external fixator. Case 1 was a 29-year-old man with a tibial defect 11 cm in length, while case 2 was a 16-year-old girl with a 15-cm-long defect. Bone transport distraction osteogenesis was initiated for the both cases on day 14 following resection of the tibial osteosarcoma. Bone transport distraction in case 1 and 2 was continued for 16 and 28 months, respectively, and the patients were followed up for 51 and 56 months, respectively. The two patients did not exhibit any signs of tumor recurrence or tumor metastasis during the follow-up period. The Musculoskeletal Tumor Society functional scores at final follow-up visits were 22 and 18 for case 1 and 2, respectively. Based on the experience gained in these 2 cases, a bone transport is a viable option for the reconstruction of large tibial defects following osteosarcoma resection.

Zinc phthalocyanine encapsulated in polymer micelles as a potent photosensitizer for the photodynamic therapy of osteosarcoma

Zinc phthalocyanine (ZnPc) is a highly potent second-generation photosensitizer for cancer photodynamic therapy (PDT) with attractive photo-physical and photo-chemical properties. However, poor solubility and strong trend of crystallization prevent it from loading in most of drug delivery systems and hamper its further application. Herein, to overcome this problem, an amphiphilic block copolymer poly(ethylene glycol)-poly[2-(methylacryloyl)ethylnicotinate] (PEG-PMAN) with aromatic nicotinate is used to load ZnPc for their π-π interactions. The formed PEG-PMAN/ZnPc nanoparticle (PPZ) dramatically increases reactive oxygen species production in osteosarcoma cells after light irradiation, causes mitochondrial injury and promotes cell cycle arrest at G2/M, leading to a 100-fold cytotoxicity improvement comparing with free ZnPc. The excellent therapeutic effectiveness and safety of PPZ are also proved by in vivo experiments operating on osteosarcoma model. The finding above indicates that PPZ has promising clinical applications as a next-generation photosensitizer in PDT of osteosarcoma.

Estrogen receptor β exhibited anti-tumor effects on osteosarcoma cells by regulating integrin, IAP, NF-kB/BCL-2 and PI3K/Akt signal pathway

This study aimed to investigate the effects of Estrogen receptor β (ERβ) on osteosarcoma cells, and explore the regulatory mechanisms involved in this process. Osteosarcoma U2-OS cells consisted four groups, and treated by E2, E2 + LY294002 (ERβ agonists), E2 + ERβ siRNA, E2 + ERβ siRNA + LY294002, respectively. Cell counting kit 8 (CCK-8) assay was performed to detect the cell viability of U2-OS cells in each group. The effects of ERβ on the migration and invasion ability of U2-OS cells were examined by wound healing assay and transwell cell culture chamber, respectively. The expression of Inhibitor of apoptosis protein (IAP) and integrin α5 in U2-OS cells of each group was detected by quantitative RT-PCR, and the expression of phosphorylated p65 (p-p65), p-AKT and Bcl-2 was detected by western blotting. The cell viability, migration and invasion ability of U2-OS cells were significantly increased by ERβ siRNA, but inhibited by ERβ agonists LY294002 (p < 0.05). ERβ siRNA significantly downregulated Integrin α5 and unregulated IAP in U2-OS cells (p < 0.05). The expression of p-p65, p-AKT and Bcl-2 was significantly reduced by LY294002, but increased by ERβ siRNA (p < 0.05). In conclusion, ERβ exhibited obvious anti-tumor effects on osteosarcoma cells by regulating integrin, IAP, NF-kBBCL-2 and PI3K/Akt signal pathway.

Effect of 17β-estradiol on the migration ability of human osteosarcoma U2OS cells

Background: To investigate the effect of 17β-estradiol on the migration ability of human osteosarcoma U2OS cells. Methods: Six concentrations of 17β-estradiol were tested in the U2OS cells, and the minimum concentration that could significantly affect the cells’ migration ability was determined by CCK-8 growth assay and cell scratch test. Furthermore, five concentrations of 17β-estradiol were used to detect the cells’ proliferation and migration ability by CCK-8 growth test, cell scratch test, transwell invasion assay, and crystal violet staining. Results: Cell viability decreased with increasing concentrations of 17β-estradiol at 24 h, and also exhibited significant changes at the treatment concentration of 1/25×10 −10 M in the CCK-8 test. The cell scratch test and crystal violet staining showed that 17β-estradiol (10 −10 M) can significantly inhibit the migration ability of U2OS cells; the transwell invasion assay showed that with increasing concentrations of 17β-estradiol, the number of invading cells began to decrease significantly at the concentration of 1/25×10 −10 M. Conclusions: 17β-estradiol can inhibit the migration of U2OS cells, starting at a concentration of 10 −10 , and in a concentration-dependent manner.

Paeoniflorin induces G2/M cell cycle arrest and caspase-dependent apoptosis through the upregulation of Bcl-2 X-associated protein and downregulation of B-cell lymphoma 2 in human osteosarcoma cells

Paeoniflorin (PF), extracted from the peony root, has been proved to possess antineoplastic activity in different cancer cell lines. However, it remains unclear whether PF has an antineoplastic effect against osteosarcoma cells. The present study investigated the effects and the specific mechanism of PF on various human osteosarcoma cell lines. Using the multiple methods to detect the activity of PF on HOS and Saos-2 human osteosarcoma cell lines, including an MTS assay, flow cytometry, transmission electron microscopy and western blotting, it was demonstrated that PF induces inhibition of proliferation, G2/M phase cell cycle arrest and apoptosis in the osteosarcoma cell lines in vitro, and activation of cleaved-caspase-3 and cleaved-poly (ADPribose) polymerase in a dose-dependent manner. Furthermore, the pro-apoptotic factors Bcl-2 X-associated protein and BH3 interacting domain death agonist were uregulated, while the anti-apoptotic factors B-cell lymphoma 2 (Bcl-2) and Bcl-2-extra large were downregulated. In conclusion, these results demonstrated that PF has a promising therapeutic potential in for osteosarcoma.

Bone transport for reconstruction of large bone defects after tibial tumor resection: a report of five cases

This study was performed to explore the clinical efficacy of bone transport using external fixation for treatment of large bone defects after tibial tumor resection in five patients. Bone transport started 14 days postoperatively at 1 mm/day and was adjusted according to the callus-to-diameter ratio. The bone transport time, bone graft fusion, relapse, and metastasis were recorded. Clinical efficacy was evaluated using the Musculoskeletal Tumor Society (MSTS) scoring system. The tumors included osteosarcoma (n=2), Ewing sarcoma (n=1), malignant schwannoma (n=1), and hemangioma (n=1). The average bone defect length after resection was 11.6 cm. The five patients were followed up for an average of 50.8 months, and the average bone transport time was 15.5 months. Three patients who underwent postoperative chemotherapy were followed for 22.7 months, and two who did not undergo chemotherapy were followed for 4.75 months. Four patients underwent iliac bone grafting, and one underwent vascular pedicle fibular transplantation. The average MSTS score was 21.2 (19.3 for patients who underwent chemotherapy and 24.0 for patients who did not). No relapse or metastasis was observed. Bone transport is effective for reconstruction of large bone defects after tibial tumor resection as well as tibial malignancies with high doses of chemotherapy.

Risk Factors and Prognosis of Surgery for Spinal Metastasis

ObjectiveTo evaluate the risk factors and prognosis of surgery for spinal metastasis.MethodsA retrospective analysis was performed for 63 patients with spinal metastasis who underwent surgical treatment between June 1992 and June 2002. Forty-one patients underwent anterior en-bloc or partial resection, decompression and reconstruction with internal fixation of the spine. Laminectomy and decompression with internal fixation were done in 8 patients. One-stage anterior-posterior en-bloc resection and decompression followed by reconstructive stabilization were conducted in 14 patients.ResultsAfter foiiow-up for more than 6 months, postoperative radiological evaluation revealed that spinal stabilization was evident in all patients. Fiftyseven (91.9%) patients benefited with quality of life significantly improved through pain alleviation, and 41 (66.1% ) patients improved in their neurological status. No serious complications were observed in surgery. The mean survival time after surgery was 6 months in patients with lung and liver carcinoma, 15 months with breast, prostate, and stomach carcinoma as-well as the other miscellaneous malignancies, and 28 months with thyroid and kidney carcinoma. Differences were significant among the 3 groups (P< 0.01).ConclusionSurgical treatment for spinal metastasis is able to relieve neurological symptoms and improve the quality of life. The survival time is related to the site of the primary tumor; shorter survival in lung and liver carcinoma, longer in breast, prostate, stomach carcinoma and longest in thyroid and kidney carcinoma.