BMPR2 and HIF1-α overexpression in resected osteosarcoma correlates with distant metastasis and patient survival

Objective： Bone morphogenetic protein receptor 2（BMPR2） and hypoxia-inducible factor 1-α（HIF1-α） existed abnormal expression in several types of cancer. However, their expressions and related roles in osteosarcoma are largely unknown.Methods：To investigate the clinical significance of BMPR2 and HIF1-αin osteosarcoma,we analyzed their expression levels in 103 osteosarcoma specimens by immunochemistry.Meanwhile,we conducted a follow-up to examine the metastatic behavior and overall survival（OS）of osteosarcoma patients.Results：Among 103 tissues,61 cases had BMPR2-positive expression and 57 cases had HIF1-αpositive expression.A significant correlation was noticed between BMPR2 and HIF1-αexpression in osteosarcoma specimens（P=0.035）.Receiver-operating characteristic（ROC）curves were calculated to investigate the predictive value of the two markers in tumor metastasis.By means of univariate and multivariate analysis,BMPR2 and HIF1-αexpression,as well as higher tumor grade,were identified as significant risk factors for OS in patients with osteosarcoma.Kaplan-Meier survival analysis revealed that the patients with BMPR2 and HIF1-αpositive expression had worse OS compared with patients with BMPR2-negative or HIF1-α-negative staining.Conclusions：It can be concluded that BMPR2 and HIF1-αexpression is highly correlated with metastatic behavior in patients with osteosarcoma and can serve as predictive markers for metastasis and OS of these patients.

STIM1 expression is associated with osteosarcoma cell survival

Objective: To examine the role of store-operated calcium entry(SOCE) and stromal interaction molecule 1(STIM1) in survival and migration of osteosarcoma cells and investigate what blockade of store-operated Ca^(2+)contributes to the regulation of osteosarcoma cells.Methods: First, we examined the expression levels of STIM1 in osteosarcoma cell lines by Western analysis and in tissue specimens by immunohistochemistry. Second, we investigated the effect of SOCE and STIM1 on osteosarcoma cell viability using MTS assays and on cell proliferation using colony formation. Third, we investigated the role of SOCE and STIM1 in cell migration using wound healing assays and Boyden chamber assays. Finally, we studied the effect of SOCE on the nuclear factor of activated T-cells cytoplasmic 1(NFATc1)activity by luciferase assays.Results: STIM1 was overexpressed in osteosarcoma cell lines and tissue specimens and was associated with poor survival of osteosarcoma patients. Also, inhibition of SOCE and STIM1 decreased the cell viability and migration of osteosarcoma cells. Furthermore, our results showed that blockade of store-operated Ca^(2+) channels involved down-regulation of NFATc1 in osteosarcoma cells.Conclusions: STIM1 is essential for osteosarcoma cell functions, and STIM1 and Ca^(2+) entry pathway could be further explored as molecular targets in the treatment of osteosarcoma.

Limb-salvage treatment of malignant pelvic bone tumor in China for past 20 years

Resection of malignant pelvic bone tumors poses a major technique challenge for orthopedic oncologists due to the large tumor size which is undetectable at the early-onset and local complex anatomy with the severe extension to major neurovascular structures and intestinal and urinary tracts.[1]Traditionally,malignant pelvic bone tumors were resected by the hindquarter amputation and the procedure obviously influenced the detrimental cosmetic and physical outcomes.More attempts have been made to perform the limb-salvage and improve the reconstruction of the pelvis after tumor resection.However,the abundant clinical experience could not be accumulated at the single tumor center due to the low incidence of pelvic bone tumors.Furthermore,the poor prognosis previously occurred to patients with tumors due to the anatomic complexity and scanty clinical experience.With the development of surgical skills and related discipline,many hospitals,especially Musculoskeletal Tumor Center of Peking University People’s Hospital(PKUPH),gathered a great deal of surgical experience of resecting the malignant pelvic tumors in the past two decades in China.The overall survival and limb-salvage rates and lower extremity function were significantly improved by more effects of many orthopedic oncologists in China in the past years.The present article was to review the limb-salvage surgery for the malignant pelvic tumors in the past two decades.

Intradural spinal seeding and fatal progression of a sacrococcygeal chordoma： a case report

Chordoma as a rare malignant tumor arising from remnants of the fetal notochord accounts for 1%-4%of primary bone tumors. It is usually predominant in males. Local recurrences are common （44%-78%） and distant metastases may occur years after the initial presentation. The reported rates of metastases range from 10% to 48%, which are usually accompanied by a sacrococcygeal chordoma. Cases of surgical seeding and intradural spinal seeding also have been reported climcally. To our knowledge, the present case is the first one concerning cerebrospinal fluid metastases and fatal progression of a sacrococcygeal chordoma.