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Takafumi Ueda

Publications and source records attributed to Takafumi Ueda.

30 records · Page 2Linked to original sources

Expression of dentin matrix protein 1 in tumors causing oncogenic osteomalacia.

Oncogenic osteomalacia, which is characterized by renal phosphate wasting, low serum 1, 25-dihydroxyvitamin D, and osteomalacia, is caused by mesenchymal neoplasms that are termed phosphaturic mesenchymal tumors (PMTs). As PMTs are usually small and lack specific histological features, the pathological identification of PMTs is difficult. Dentin matrix protein 1 (DMP1) is an acidic phosphoprotein expressed in mineralized tissues including bone, tooth, and hypertrophic cartilage. Increased expression of DMP1 gene in PMTs has been reported by using differential cDNA screening. In the present study, DMP1 expression in PMTs and other soft tissue tumors was analyzed immunohistochemically to verify its utility in the differential diagnosis of PMTs. Anti-DMP1 polyclonal antibody was raised against the C-terminal sequence of DMP1. Three cases with PMTs and 11 other soft tissue tumors (two malignant hemangiopericytomas, three solitary fibrous tumors, three synovial sarcomas, and three malignant peripheral nerve sheath tumors) were analyzed for DMP1 expression. DMP1 expression was observed in all of the three cases with PMTs, but never found in other soft tissue tumors examined. DMP1 was detected in the extracellular matrix with myxomatous features or around capillary vessels, and in dystrophic calcified sites. Paranuclear DMP1 staining in the tumor cells was also observed. These findings indicate that DMP1 immunohistochemistry is a useful tool for identifying PMTs.

Adult↗

Myxoid liposarcoma with adipocytic maturation: detection of TLS/CHOP fusion gene transcript.

This report describes a 49-year-old woman with a well-circumscribed nodule of liposarcoma. The patient noticed a soft, slowly growing mass at the right sural region. Both axial computed tomography and magnetic resonance imaging revealed a soft tissue tumor consisting of nonfatty lesion measuring 5 x 3 x 3 cm circumscribed by a 1-cm thickened fatty area. Histologically, the tumor was made of 2 distinct components: the inner component of the tumor was a classic myxoid liposarcoma with numerous lipoblasts; the outer component was a lipoma-like lesion consisting of mature adipocytes without atypical nuclei. Immunohistochemically, MDM2 overexpression was observed and p53 immunophenotype was negative in both components. Molecular analysis revealed that type 1 TLS/ CHOP fusion gene transcript, characteristic of myxoid/round cell liposarcoma, was detected in both areas.

Adipocytes↗

Cystic synovial sarcomas: imaging features with clinical and histopathologic correlation.

OBJECTIVE: To characterize the radiological and clinicopathologic features of cystic synovial sarcoma. DESIGN AND PATIENTS: Seven patients with primary cystic synovial sarcoma were evaluated. Computed tomography (CT) and magnetic resonance (MR) imaging were undertaken at the first presentation. The diagnosis of synovial sarcoma was made on the basis of histological examinations followed by molecular analysis. Radiological and clinicopathologic findings were reviewed. RESULTS: CT showed well-defined soft tissue mass without cortical bone erosion and invasion. Calcification was seen at the periphery of the mass in three cases. T2-weighted MR images showed multilocular inhomogeneous intensity mass in all cases, five of which showed fluid-fluid levels. On gross appearance, old and/or fresh hematomas were detected in six cases. In the one remaining case, microscopic hemorrhage in the cystic lumen was proven. Four cases had poorly differentiated areas. In five cases prominent hemangiopericytomatous vasculature was observed. Histologic grade was intermediate in one tumor and high in six. One case had a history of misdiagnosis for tarsal tunnel syndrome, one for lymphadenopathy, two for sciatica and two for hematoma. CONCLUSION: All cystic synovial sarcomas demonstrated multilocularity with well-circumscribed walls and internal septae. Synovial sarcoma should be taken into consideration in patients with deeply situated multicystic mass with triple signal intensity on T2-weighted MR imaging.

Adolescent↗

Monoclonal antibody to parathyroid hormone-related protein induces differentiation and apoptosis of chondrosarcoma cells.

We investigated the effects of treatment with anti-parathyroid hormone-related protein (1-34) monoclonal murine antibody (anti-PTHrP MoAb) on apoptosis and the differentiation of chondrosarcoma HTB-94 cells. Treatment with anti-PTHrP MoAb accelerated apoptosis of HTB-94 cells in a dose-dependent manner, and anti-PTHrP MoAb also promoted the chondrogenic differentiation of HTB-94 cells. The induction of apoptosis by anti-PTHrP MoAb via imbalance of Bcl-2/Bax ratio and activation of caspase-3 may provide a mechanistic explanation for its potential antitumor effects. Our results suggest the possibility that anti-PTHrP MoAb may be beneficial as a new treatment for chondrosarcoma.

Antibodies, Monoclonal↗

Unusual skeletal metastases from myxoid liposarcoma only detectable by MR imaging.

We present two cases of skeletal metastases from myxoid liposarcoma, occurring several years after treatment of the primary tumors in the lower limb. The present two case reports have unusual radiological features only detectable by MR imaging and not by plain radiographs or bone scans. From the present two cases, we found that a negative plain radiograph of the spine or a negative bone scan could not exclude skeletal metastases from myxoid liposarcoma, and MRI was a more sensitive screening procedure for their detection, especially in T1-weighted images. Unusual radiological features of skeletal metastases from myxoid liposarcoma are not well documented and only a few cases have been previously reported. Our aim is to document two more patients exhibiting the unusual radiological features of skeletal metastases from myxoid liposarcoma to improve their early detection and management.

Adult↗

Overexpression of the Wilms' tumor gene WT1 in human bone and soft-tissue sarcomas.

The expression levels of the Wilms' tumor gene WT1 were examined in 36 cases of various types of human bone and soft-tissue sarcomas using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). They included 12 malignant fibrous histiocytomas (MFH), 3 malignant peripheral nerve sheath tumors (MPNST), 6 synovial sarcomas (SyS), 4 myxoid liposarcomas (MyLS), one angiosarcoma (AGS), one clear cell sarcoma (CCS), and 9 osteosarcomas (OS). Eleven (92%) of 12 MFH, 2 (67%) of 3 MPNST, all (100%) of 6 SyS, 2 (50%) of 4 MyLS, one AGS, one CCS, and 5 (56%) of 9 OS cases overexpressed WT1 in the range of 1.4 x 10(-3)-3.9 x 10(-1) levels (WT1 expression level in K562 leukemic cells was defined as 1.0). Thus, 28 (78%) out of 36 various types of human bone and soft-tissue sarcomas overexpressed the WT1 gene. Immunohistochemical analysis showed positive staining for WT1 protein in all of 4 cases (one case each of MFH, MyLS, AGS and OS) with WT1 gene overexpression detected by RT-PCR analysis, demonstrating clearly that WT1 was expressed at the protein level in various types of human bone and soft-tissue sarcomas. The direct sequencing analysis of the WT1 genomic DNA showed no mutations in any of 10 exons of the WT1 gene in 8 different sarcoma samples (3 MFH, one SyS, one MyLS, one AGS, and 2 OS). The present study demonstrates that various types of human bone and soft-tissue sarcomas frequently overexpress the wild-type WT1 gene, suggesting an important role of the wild-type WT1 gene in tumorigenesis of various types of human bone and soft-tissue sarcomas.

Adult↗

Alveolar soft part sarcoma in Japan: multi-institutional study of 57 patients from the Japanese Musculoskeletal Oncology Group.

OBJECTIVE: The clinical features and the management of alveolar soft part sarcoma (ASPS) are not well known. The efficacy of chemotherapy for soft tissue sarcoma, including high-dose ifosfamide and cisplatin, has not been established yet. Some reports suggest ASPS may occur primarily in bone. METHODS: We report on a series of 57 patients with ASPS over 20 years. Their ages ranged from 7 to 75 years (mean 25). RESULTS: There were 37 females and 20 males. Thirteen lesions (23%) showed bone involvement at the primary site, and 6 of them were diagnosed as bone tumors at presentation. Thirty-seven patients had distant metastases at presentation. Tumor size, bone involvement at the primary site and the presence of metastases at presentation were prognostic indicators (p < 0.05). Marginal excision with radiotherapy or wide excision without radiotherapy achieved good local control. Chemotherapy was performed in 47 patients with different regimens. Two patients treated with intra-arterial chemotherapy regimens responded partially, but intravenous chemotherapy with high-dose ifosfamide or cisplatin failed. CONCLUSIONS: ASPS can present primarily as a bone tumor. No advantage of chemotherapy with high-dose ifosfamide or cisplatin could be demonstrated.

Adolescent↗

Clinical implications of serum C-reactive protein levels in malignant fibrous histiocytoma.

Paraneoplastic syndromes (PNSs) associated with mesenchymal tumors are uncommon. Previous reports sporadically described inflammatory PNSs with elevated serum C-reactive protein (CRP) levels and leukocytosis in patients with inflammatory malignant fibrous histiocytoma (MFH) of soft tissue; however, the relationship between other subtypes of MFH and PNS has not been extensively investigated. Forty-six patients with primary MFH of soft tissues who underwent radical surgery were retrospectively analyzed. These patients were divided into 2 groups according to preoperative serum CRP level: normal (<1.0 mg/dl) and elevated (> or = 1.0 mg/dl). The correlation between serum CRP level and several clinicopathologic factors was analyzed. Correlation between preoperative serum CRP level and metastasis-free and overall survival was also investigated by univariate and multivariate analyses. Elevated preoperative serum CRP levels were found in 65% of patients with a mean of 3.7 mg/dl. There were statistically significant relationships regarding tumor size, depth, histologic subtypes, grade, stage and metastatic rate among normal and elevated CRP groups (p < 0.001, p < 0.02, p < 0.005, p < 0.001, p < 0.001 and p < 0.05, respectively). When the tumor was removed, the elevated CRP level subsided into the normal range and other abnormal laboratory findings diminished in all cases. In 11/14 relapsed cases that showed elevated CRP preoperatively, the serum CRP level re-elevated with tumor relapse. The normal CRP group showed significantly more favorable prognosis than the elevated CRP group in metastasis-free and overall survival on univariate analysis (p < 0.02, p < 0.05, respectively). Patients with MFH frequently present with an inflammatory PNS, such as elevated serum CRP level, which can be a useful marker of disease activity and a valuable prognostic indicator.

Adult↗

Bone Metastases from Soft Tissue Sarcomas.

The incidence, distribution, time of appearance, and radiologic findings of bone metastases from soft tissue sarcomas, exclusive of lymphomas, were evaluated in 320 patients with soft tissue sarcomas. Thirty patients (9.4%) had evidence of 58 bone metastases. Five of 30 patients presented with metastases, and 25 of 30 patients developed metastases up to 66 months after presentation with a mean time interval of 21.3 months. The incidence of skeletal metastases differed among histologic subtypes of sarcomas; alveolar soft part sarcoma (5 of 8), dedifferentiated liposarcoma (2 of 4), angiosarcoma (2 of 4), and rhabdomyosarcoma (5 of 16) tended to show a higher incidence of bone metastases. The sarcomas metastasized to the regional bones close to the primary tumor in 16 (53%) of 30 patients and to the axial bones in 18 (60%). On conventional radiographs, the osseous metastases demonstrated predominantly osteolytic changes, and evidence of pathological fracture was observed in 31% of 58 metastases.

Journal Article↗

Inhibition of murine osteosarcoma cell proliferation by glucocorticoid.

The effects of glucocorticoid (GC) on the proliferation of Dunn Osteosarcoma (OS) cells were examined under in vitro culture conditions. Dexamethasone (Dex) inhibited the proliferation of Dunn OS cells in a dose-dependent manner, while the addition of anti-GC, RU486, to the culture medium in part recovered Dex-induced growth inhibition. The number of maximum binding sites (Bmax) and the dissociation constant (Kd) value of glucocorticoid receptor (GR) in Dunn OS cells were 19,560 sites/cell and 5.2 +/- 0.8 nM, respectively. RU486 competed with labeled Dex against GR at a concentration of 10(-6) M. Western blot analysis of [3H]Dex-mesylate-labeled cell homogenate and immunohistochemical staining against GR further confirmed the presence of GR. Dex treatment of Dunn OS cells resulted in apoptosis with the characteristic internucleosomal DNA cleavage shown by the DNA ladder pattern in agarose gel electrophoresis. These data demonstrate that GC inhibits the proliferation of Dunn OS cells via GR, for which one possible mechanism in vitro is induction of apoptosis.

Animals↗

Reassessment of the 1993 Osaka grading system for localized soft tissue sarcoma in Japan.

BACKGROUND: The Osaka system for soft-tissue sarcoma grading was proposed through an analysis of soft-tissue sarcoma (STS), treated from 1964 to 1989. The present study was conducted to evaluate the utility of the Osaka system under recent therapeutic regimens. PATIENTS AND METHODS: One hundred and eleven patients with localized STSs arising in the trunk and extremities (66 males and 45 females; median age 57) were selected. Histological factors, argyrophilic nucleolar organizer region (AgNOR) count and Ki-67 labeling index (LI) were evaluated for prognostic significance. RESULTS: Univariate analysis revealed that histological classification, mitotic count, cellularity, AgNOR count, and Ki-67 LI were prognostically significant for survival. Multivariate analysis revealed Ki-67 LI as an independent prognostic factor. The five-year survival rate for low-, intermediate-, and high-grade STSs in Osaka grading was 94.6%, 75.2%, and 68.4%, respectively. CONCLUSION: Osaka grading is a useful system for the decision-making of therapeutic modalities for STS.

Adult↗