Prognostic factors in localized extremity osteosarcoma: A systematic review

Aim

Finding reliable prognostic factors for osteosarcoma remains problematic. A systematic review [Davis AM, Bell RS, Goodwin PJ. Prognostic factors in osteosarcoma: a critical review. Journal of Clinical Oncology 1994; 12(2): 423–431.] showed chemotherapy response as only independent factor. We tried to identify evidence-based prognostic factors in the literature since 1992 and to establish pooled relative risks of factors.

Methods

MEDLINE and Embase search (1992–August 2006). Two reviewers independently selected papers addressing prognostic factors in localized extremity osteosarcoma, which were studied for methodological quality, and valuable new factors. An attempt was made to pool results.

Results

Of 1777 “hits”, 93 papers were studied in depth. Several “new” prognostic factors were found. Only 7 papers were of sufficient quality to analyze. Chemotherapy response, tumor size and site, alkaline phosphatase level and p-glycoprotein expression seemed to be independent factors. Some new factors looked promising.

Conclusions

Although the literature is abundant, it is disappointing that only few papers are of sufficient quality to allow hard conclusions. Because of heterogeneity of the studies pooling results is hardly possible. There is a need for standardization of studies and reports.     

The novel isoflavone 7-hydroxy-3',4'-benzoisoflavone induces cell apoptosis in human osteosarcoma cells

Osteosarcoma is the most frequent primitive malignant tumor of the skeletal system and is characterized by an extremely aggressive clinical course that lacks an effective treatment. This study is the first to investigate the anti-cancer effects of a new isoflavone-derived 7-hydroxy-3',4'-benzoisoflavone (HBI) in human osteosarcoma cells. HBI-induced cell apoptosis in human osteosarcoma cell lines. The accumulation of reactive oxygen species (ROS) is a critical mediator in HBI induced cell death. HBI also induced apoptosis signal-regulating kinase 1 (ASK1) dephosphorylation, p38, JNK and p53 phosphorylation. Transfection with ASK1, p38 and JNK small interfering RNA (siRNA) antagonized HBI-induced cell apoptosis. HBI also triggered the mitochondrial apoptotic pathway, as indicated by a change in Bax/Bcl2 ratio. Bax knockdown using a Bax siRNA strategy reduced Bax expression and subsequent cell death. In addition, ASK1, p38 and JNK siRNA reduced HBI-induced p53 phosphorylation and Bax expression. These results suggest that the ROS-ASK1-p38/JNK-p53 and Bax pathway plays a critical role in HBI's anti-cancer effects.     

Vanadium(IV) complexes inhibit adhesion, migration and colony formation of UMR106 osteosarcoma cells

Vanadium is a trace element widely distributed in the environment. In vertebrates it is mainly stored in bone tissue. The unique cellular environment in the bone and the variety of interactions that mediate cancer metastasis determine that certain types of cancer, such as breast and prostate cancer, preferentially metastize in the skeleton. Since this effect usually signifies serious morbidity and grave prognosis there is an increasing interest in the development of new treatments for this pathology. The present work shows that vanadium complexes can inhibit some parameters related to cancer metastasis such as cell adhesion, migration and clonogenicity. We have also investigated the role of protein kinase A in these processes.     

Role of p38 mitogen activated protein kinase in a model of osteosarcoma-induced pain

The focus of this work was to examine the potential role of p38 mitogen activated protein kinase (p38) in a mouse model of bone cancer (osteosarcoma) pain. To generate osteosarcoma and sham animals, osteosarcoma cells or medium were injected into the medullary canal of the femur. Initially, ipsilateral tactile allodynia was observed in both groups, but by 12 days post-surgery, thresholds in the sham group returned towards baseline while hypersensitivity in the osteosarcoma group lasted throughout the study. An increase in phosphorylated p38 was detected by western blotting in dorsal root ganglia (DRG) and spinal cord day 14 after surgery. Immunohistochemistry showed that p38 was phosphorylated in DRG and spinal dorsal horn neurons at this time point. Two doses of a selective p38 inhibitor, SCIO-469, were administered in the chow starting 5 days post-surgery and continued throughout the study. Treatment with SCIO-469 led to a decrease in osteosarcoma-induced clinical score but had no effect on the allodynia. Bone erosion and tumor growth were also examined but no significant reduction of bone erosion or tumor growth was observed in the SCIO-469 treated mice. These data suggest that the p38 signaling pathway does not play a major role in bone cancer-mediated pain.     

Orbital metastasis: a rare presentation of osteosarcoma

Non-pulmonary metastases in osteosarcoma are increasingly recognized because of improved longevity in patients receiving modern treatment. One rare site of metastasis is the orbit, with only three cases reported so far. This report describes a 16-year-old male patient, who underwent above-knee amputation for right tibial osteosarcoma and later presented with a painful protrusion of the right eyeball and near-normal vision. The uncommon features in the present case are the site of metastasis and near-normal vision.     

Immunocytochemical identification of osteogenic bone tumors by osteonectin antibodies

Summary 18 bone-forming tumours and tumour-like lesions were investigated immunocytochemically for the presence of osteonectin. A group of non-bone-forming skeletal tumours (five cartilage-forming tumours, four Ewing sarcomas and five extraskeletal sarcomas) served as controls. The studies showed that osteonectin antibodies react reliably with benign and malignant bone-forming tumours (two cases of fibrous dysplasia, three osteoid osteomas, 13 osteosarcomas). This finding was supported by protein blot studies. Osteonectin is formed by cells which do not yet possess the morphological phenotype of osteoblasts and may be regarded as a differentiation marker of the osteoblastic lineage. Only chondroid bone (tissue in which chondrocytes were surrounded by osteoid matrix containing type I and type II collagen) showed a positive reaction. All other primary skeletal tumours and extraskeletal soft tissue tumours were completely negative.     

lncRNA CASC19靶向miR-490-3p调控骨肉瘤细胞增殖、迁移和侵袭的分子机制

【摘要】 目的 探讨lncRNA CASC19对骨肉瘤细胞的增殖、迁移和侵袭的影响以及潜在的作用机制。 方法 实验设置si con组、si CASC19组、pcDNA组、pcDNA CASC19组、miR con组、miR 490 3p组、si CASC19+anti miR con组、si CASC19+anti miR 490 3p组;qRT PCR检测miR 490 3p和CASC19的表达水平;Western blot检测蛋白表达;MTT法检测细胞活性;Transwell检测各组细胞迁移和侵袭;双荧光素酶报告基因检测实验检测荧光活性。 结果 骨肉瘤细胞MG63、U2 OS、OS187中miR 490 3p低表达,CASC19高表达（P＜005）;过表达miR 490 3p或干扰CASC19表达可抑制骨肉瘤细胞MG63增殖、迁移和侵袭。CASC19靶向调控miR 490 3p的表达,抑制miR 490 3p表达能逆转干扰CASC19对骨肉瘤细胞MG63增殖、迁移、侵袭的抑制作用。 结论 lncRNA CASC19可抑制骨肉瘤细胞的增殖、迁移和侵袭,其机制可能与靶向调控miR 490 3p有关,将可为骨肉瘤的预防和治疗提供新靶点。     

DACH1 Expresison in Osteosarcoma and Its Relationship with Proliferation and Angiogenesis

The aim of this study was to investigate the expression of DACH1 in osteosarcoma as well as its relationship with cell proliferation and angiogenesis in the tumor. DACH1 expression was detected by immunohistochemical staining in the serial sections of the osteosarcoma. The microvessel density (MVD) was counted by CD34 immunohistochemical staining, and immunohistochemical staining of PCNA staining showed the cell proliferation. The impacts of DACH1 expression on tumor proliferation and angiogenesis were evaluated by statistics. The DACH1 had different expression patterns in different osteosarcoma. Conventional osteosarcoma showed stronger DACH1 staining (conventional vs. parosteal: P = 0.037; conventional vs. periosteal: P = 0.028) and more PCNA-positive tumor cells than parosteal and periosteal osteosarcoma (conventional vs. parosteal: P = 0.041; conventional vs. periosteal: P = 0.045), the difference was significant. In addition, conventional osteosarcoma showed more cytoplasmic staining of DACH1 than parosteal and periosteal (conventional vs. parosteal: P = 0.023; conventional vs. periosteal: P = 0.030). Parosteal and periosteal osteosarcoma showed no significant difference in DACH1 expression and cell proliferation index. On the other hand, DACH1 different expression patterns showed significantly different impacts on angiogenesis. In spite of the different subtypes of osteosarcoma, the MVD showed a significant difference in cytoplasmic and nuclear expression patterns of DACH1 (nuclear expression vs. cytoplasmic expression: 5.72 ± 1.19 vs. 9.65 ± 1.24, P = 0.042). Moreover, in the conventional osteosarcoma, the MVD also showed a significant difference in DACH1 cytoplasmic and nuclear staining (nuclear expression vs. cytoplasmic expression: 5.58 ± 0.71 vs. 13.65 ± 1.30, P = 0.019). However, the DACH1 expression intensity showed no significant different impacts on MVD of all kinds of osteosarcoma. DACH1 had different expression patterns and intensity. Cytoplasmic and nuclear expression of DACH1 might play different roles in cell proliferation and angiogenesis of osteosarcoma. Cytoplasmic DACH1 might promote cell proliferation and be associated with angiogenesis.     

皮质旁骨肉瘤术后复发1例

患者女,30岁,8月前发现左股骨下端皮质旁骨肉瘤(图1),经病理证实.因病人要求保留患侧肢体拒绝截肢,故行左股骨下段切除并人工全膝关节置换.近1周来发现左腘窝上方软组织内质硬肿物,触之可移动.无其它不适症状.     

外伤性骨肉瘤病例报道1例及相关文献回顾

患者,男,21岁,因左侧大腿远端摔伤后出现一软组织肿物10年余,于2012年1月26日来我院就诊。患者10年前骑自行车时摔伤左侧大腿远端,摔伤2个月后发现左侧大腿远端前方一组织肿物,约花生粒大小,质硬,与周围组织分界尚清,局部无红肿,屈膝时有酸痛,压痛不明显,发病至今未行特殊治疗,今为求手术切除肿物入院治疗。