ユビキリン２は低酸素ストレスに耐性を示すことで骨肉腫の増殖を促進させる

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.博士（医学）・甲第637号・平成27年5月28日Copyright © Spandidos Publications 2015本文のリンク：http://dx.doi.org/10.3892/or.2015.378

ヒト間葉系幹細胞はエオタキシン3/CCR3経路を介して前立腺癌細胞の浸潤能を増加させる

This study aimed to clarify the role of mesenchymal stem cells (MSCs) as a component of the cancer microenvironment. We investigated the homing-related chemokine expression levels of MSCs treated with a prostate cancer cell line (PC-3) -conditioned medium. Among several homing chemokines, an antibody array revealed that expression of eotaxin-3 (but not eotxin-1 and -2) was highly enhanced in MSCs treated with PC-3-conditioned medium. A gene expression array showed significantly increased expression of CCR3, a receptor of eotaxin-3, in PC-3. In a matrigel invasion assay, interferon-gamma, a specific inhibitor of eotaxin-related homing, significantly reduced the transmigration of PC-3 cells, under co-cultured condition with MSCs, in a dose-dependent manner (P < 0.05). Consistent with these results, anti-CCR3 antibody successfully reduced PC-3 migration under the co-cultured condition. These findings suggest that MSCs to modulation of the invasive potential of prostate cancer cells via the eotaxin-3/CCR3 axis.博士（医学）・乙第1424号・平成30年11月30日© 2018 Elsevier GmbH. All rights reserved

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

Current Concepts in the Treatment of Giant Cell Tumors of Bone

Simple Summary According to the 2020 World Health Organization classification, a giant cell tumor of bone is an intermediate malignant bone tumor. Denosumab treatment before curettage should be avoided due to the increased risk of local recurrence. Administration of denosumab before en bloc resection of the giant cell tumors of the pelvis and spine facilitates en bloc resection. Nerve-sparing surgery after embolization is a possible treatment for giant cell tumors of the sacrum. Denosumab therapy with or without embolization is indicated for inoperable giant cell tumors of the pelvis, spine, and sacrum. A wait-and-see approach is recommended for lung metastases at first, then denosumab should be administered to the growing lesions. Radiotherapy is not recommended owing to the risk of malignant transformation. Local recurrence after 2 years or more should be indicative of malignant transformation. This review summarizes the treatment approaches for non-malignant and malignant giant cell tumors of bone. The 2020 World Health Organization classification defined giant cell tumors of bone (GCTBs) as intermediate malignant tumors. Since the mutated H3F3A was found to be a specific marker for GCTB, it has become very useful in diagnosing GCTB. Curettage is the most common treatment for GCTBs. Preoperative administration of denosumab makes curettage difficult and increases the risk of local recurrence. Curettage is recommended to achieve good functional outcomes, even for local recurrence. For pathological fractures, joints should be preserved as much as possible and curettage should be attempted. Preoperative administration of denosumab for pelvic and spinal GCTBs reduces extraosseous lesions, hardens the tumor, and facilitates en bloc resection. Nerve-sparing surgery after embolization is a possible treatment for sacral GCTBS. Denosumab therapy with or without embolization is indicated for inoperable pelvic, spinal, and sacral GCTBs. It is recommended to first observe lung metastases, then administer denosumab for growing lesions. Radiotherapy is associated with a risk of malignant transformation and should be limited to cases where surgery is impossible and denosumab, zoledronic acid, or embolization is not available. Local recurrence after 2 years or more should be indicative of malignant transformation. This review summarizes the treatment approaches for non-malignant and malignant GCTBs

What&apos;s new in the management of metastatic bone disease

Metastatic bone disease is a common complication of malignant tumours. As cancer treatment improves the overall survival of patients, the number of patients with bone metastases is expected to increase. The treatments for bone metastases include surgery, radiotherapy, and bone-modifying agents, with patients with a short expected prognosis requiring less invasive treatment. Patients with metastatic bone disease show greatly varying primary tumour histology, metastases sites and numbers, and comorbidities. Therefore, randomised clinical trials are indispensable to compare treatments for these patients. This editorial reviews recent findings on the diagnosis and prognosis prediction and discusses the current treatment of patients with metastatic bone disease