Shinji Tsukamoto

Mesenchymal stem cells promote tumor engraftment and metastatic colonization in rat osteosarcoma model.

Although mesenchymal stem cells (MSCs) are considered to be the cells of origin for most sarcomas, the role of MSCs as a source of tumor stroma is not fully understood in this tumor type. The current study investigated whether MSCs affect the tumor growth and metastatic ability in rat osteosarcoma model. Results from subcutaneous co-implantation of rat osteosarcoma COS1NR cells, established in our laboratory, with rat MSCs isolated from femur bone marrow showed that the incidence of tumor formation and tumor growth rate was higher until 5 weeks compared to COS1NR cell inoculation alone. However, no difference was observed in tumor growth afterwards and in the number of metastatic nodules at 9 weeks (0.75 vs. 1.2). Intravenous MSC injection at weeks 3 and 5 after subcutaneous inoculation of COS1NR cells significantly increased the number of lung nodules in the group with MSC injection compared to the group without MSC injection (17.33 vs. 2.0), while no difference was observed in subcutaneous tumor growth between those groups. Pathway analysis from gene expression profile identified that genes involved in focal adhesion, cytokine-cytokine receptor and extracellular matrix-receptor pathways such as CAMs (ICAM and VCAM)-integrins were highly expressed in MSCs, possibly participating in the tumor progression of osteosarcoma. These results suggest that MSCs could provide a source of microenvironments for osteosarcoma cells, and might enhance the ability of settlement and colonization which lead to early onset of growth and metastasis, possibly through their activated pathways interaction.

Total talar replacement following collapse of the talar body as a complication of total ankle arthroplasty: A case report

Collapse of the talar body is a serious complication of total ankle arthroplasty. As the degree of osteoporosis increases, collapse is more likely, especially in patients with rheumatoid arthritis1. A paucity of revision implants, poor soft-tissue coverage and vascularity, and decreased bone stock make revision of a failed total ankle arthroplasty more challenging than revision of a failed hip or knee arthroplasty2. Kotnis et al.2 reported that revision is inadvisable in the presence of large osseous defects because they increase the chances of malalignment and instability, with resultant early failure. Johl et al.3 recommended a tibiotalocalcaneal arthrodesis with a short retrograde femoral nail as the treatment for aseptic loosening after a total ankle replacement with extensive bone loss because of the stability that is created and the low risk of pseudarthrosis. However, the major disadvantages of a tibiotalocalcaneal arthrodesis are a certain degree of shortening and a stiff foot4. In the case reported here, to restore the range of motion and to prevent degenerative changes in the distal joints such as the tarsometatarsal and metatarsophalangeal joints, we replaced a collapsed talar body and previous implants with a total talar prosthesis. The patient was informed that data concerning the case would be submitted for publication, and she consented. A fifty-six-year-old woman who had been managed for rheumatoid arthritis for twenty years presented to our institution because she had had increasing pain and loss of function in the left ankle for the previous year. Extensive changes in the ankle and subtalar joints that were typical of rheumatoid arthritis were verified with radiography, and a total ankle …

Comparison of Gene Expression Profiling in Sarcomas and Mesenchymal Stem Cells Identifies Tumorigenic Pathways in Chemically Induced Rat Sarcoma Model

Mesenchymal stem cells (MSCs) are believed to be the cell of origin for most sarcomas including osteosarcoma and malignant fibrous histiocytoma (MFH/UPS). To identify the signaling pathways involved in sarcoma pathogenesis, we compared gene expression profiles in rat osteosarcoma and MFH cells with those in syngeneic rat MSCs. Analysis of genes that characterize MSCs such as CD44, CD105, CD73, and CD90 showed higher expression in MSCs compared to sarcomas. Pathways involved in focal and cell adhesion, cytokine-cytokine receptors, extracellular matrix receptors, chemokines, and Wnt signaling were down-regulated in both sarcomas. Meanwhile, DNA replication, cell cycle, mismatch repair, Hedgehog signaling, and metabolic pathways were upregulated in both sarcomas. Downregulation of p21Cip1 and higher expression of CDK4-cyclinD1 and CDK2-cyclinE could accelerate cell cycle in sarcomas. The current study indicated that these rat sarcomas could be a good model for their human counterparts and will provide the further insights into the molecular pathways and mechanisms involved in sarcoma pathogenesis.

Arthroscopic ankle arthrodesis for hemophilic arthropathy: two cases report.

In the second decade of life, the ankle joint can be considered as the most common site for haemophilic arthropathy. To the best of our knowledge, no detailed reports have been published regarding arthroscopic ankle arthrodesis with haemophilic arthropathy. The aim of this paper is to report the outcomes of arthroscopic ankle arthrodesis in haemophilic arthropathy of the hindfoot. We performed three arthroscopic ankle arthrodeses in two patients. Case 1 was a 26-year-old man and case 2 was a 25-year-old man. The follow-up periods ranged from 2 year and 4 months to 6 years and one month. Union was obtained in all three ankles. All the arthroscopic ankle arthrodeses stopped or significantly reduced recurrent joint bleeding. With our procedure, we achieved pain relief and walking ability improvement. The mean American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale scores were 39 (range: 32-52) points preoperatively and 80 (range: 74-92) points postoperatively. Our cases achieved high satisfaction levels with pain relief and minimal complications for arthroscopic ankle arthrodesis, and case 2 who originally underwent arthroscopic arthrodesis of the left ankle demanded the same operation for his right ankle. We consider that arthroscopic ankle arthrodesis is an effective technique for haemophilic arthropathy.

Hibernoma of the axillary region: a rare benign adipocytic tumor

Hibernoma is a rare benign tumor considered to arise from remnants of fetal brown adipose tissue. It tends to occur in sites where brown fat persists beyond fetal life, such as the interscapular region, but can occur in sites where brown fat is usually absent in adults. Clinicallywell, hibernomas are slow-growing, asymptomatic tumors. However, unlike lipomas, MRI findings sometimes mislead clinicians to diagnose a malignant neoplasm. We describe a 63-year-old male with an axillary hibernoma involving the brachial neurovascular bundles and mimicking a well-differentiated liposarcoma, from which it should be distinguished.

How safe and effective is denosumab for bone giant cell tumour

Recent clinical studies have suggested that denosumab is associated with beneficial tumour response, surgical down-staging, and reduced surgical morbidity in patients with giant cell tumour of bone. However, these studies reported results of patients still on denosumab treatment, or patients after denosumab treatment but with a short follow-up. Other studies reported that the new osseous tumour matrix and thickened cortical bone that develop with denosumab treatment does not allow the surgeon to delineate the true extent of the tumour, and probably increases the risk for local recurrence. A study showed that cell proliferation is only diminished by denosumab; the cells continue to proliferate in vitro, albeit at a slower rate. More importantly, nine cases of malignant transformation of GCT during denosumab therapy without previous radiation exposure have been reported; inhibition of RANKL may increase the risk of new malignancies due to immunosuppression. With these concerns in mind, this article is an attempt to put essential information in one place, creating a comprehensive review that the curious reader would find interesting and informative.

Chemotherapy improved prognosis of mesenchymal chondrosarcoma with rare metastasis to the pancreas.

Extraskeletal mesenchymal chondrosarcoma is rare and metastasis to the pancreas is extremely rare, with only four cases reported in the literature. The therapeutic effectiveness of chemotherapy remains uncertain. We report a 39-year-old man with extraskeletal mesenchymal chondrosarcoma of the buttock, who had metastases to the pancreas, bones, and lung. He underwent distal pancreatectomy, resection of the buttock tumor, and chemotherapy. He had a good response to chemotherapy and survived for about 3 years after surgery.

Ubiquilin 2 enhances osteosarcoma progression through resistance to hypoxic stress

Ubiquilin 2 (UBQLN2), a member of the ubiquitin-like protein family (ubiquilins), maintains protein homeostasis. Although UBQLN2 has been implicated in the pathogenesis of neurodegenerative diseases, it is also associated with malignant tumors. Therefore, we examined whether UBQLN2 plays a role in human osteosarcoma. The human osteosarcoma cell line MG63 was transfected with UBQLN2 siRNA and cultured under hypoxic conditions. The rat osteosarcoma cell line COS1NR was inoculated into Fischer 344 rats, followed by injection of UBQLN2 siRNA with atelocollagen. An immunohistochemical analysis of UBQLN2 was performed using 34 cases of human high-grade osteosarcomas, and metastasis-free survival was estimated by the Kaplan-Meier method. Silencing of UBQLN2 by siRNA transfection under hypoxia led to activation of JNK and p38, resulting in induction of apoptosis in the osteosarcoma cell line MG63. Injection of UBQLN2 siRNA suppressed tumor growth in the rat osteosarcoma model, followed by apoptosis induction. The immunohistochemical examination revealed that high UBQLN2 expression was significantly associated with the unfavorable metastasis-free survival of osteosarcoma patients. UBQLN2 plays an important role in resistance to hypoxic stress and enhances tumor progression in osteosarcoma. UBQLN2 may be a new molecular target for chemotherapeutics and a useful clinicopathological marker in human osteosarcoma.

Development of high-grade osteosarcoma in a patient with recurrent giant cell tumor of the ischium while receiving treatment with denosumab

Malignant transformation of giant cell tumor of bone (GCTB) without radiotherapy exposure is exceptionally rare, occurring in less than 1% of GCTBs. The safety and efficacy of denosumab in patients with GCTB was recently reported. We herein report a case of a benign recurrent GCTB with an H3F3A mutation that underwent secondary malignant transformation during treatment with denosumab. A 29-year-old woman underwent curettage of a GCTB of the left ischium in 2005. Ten years after the first surgery, the GCTB recurred locally. We started treatment with denosumab. During the first 5 months of treatment, we observed a demarcated area of osteosclerosis in the recurrent lesion, and the patients clinical condition improved. At 6 months, however, the patient developed pain, and a rapidly growing mass was detected by computed tomography. An incisional biopsy was performed. Histologic analysis showed a high-grade osteosarcoma. The patient developed lung metastases and died soon after beginning chemotherapy. The mechanism of sarcomatous transformation of GCTB during denosumab therapy is unclear. These findings suggest that the scientific community should be aware of the possible malignant transformation of GCTB during denosumab treatment.

Type 1 neurofibromatosis with a giant intrathoracic lesion: a case report with 25 years of follow-up.

We report a case of neurofibromatosis 1 with a huge intrathoracic lesion followed-up for 25 years. When the patient was 5 years of age, we performed a partial resection as an excisional biopsy. Microscopically, small spindle cells and collagen were spread between fat cells. A CT scan revealed a large intrathoracic mass, but tumor growth increasingly retarded as the patient grew older. During the entire 25-year follow-up period, from 5 to 30 years of age, the patient showed no neurological signs or other clinical symptoms. The findings of our case suggest that for a neurofibromatosis 1 patient, a good prognosis can be expected even if a huge destructive intrathoracic intrusion is detected. To assess the risk of malignant transformation, follow-up is required, accompanied by appropriate diagnostic modalities and physical examinations.