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Takafumi Ueda

Publications and source records attributed to Takafumi Ueda.

At least 19 recordsLinked to original sources
PubMed2007

Clear cell sarcoma of tendons and aponeuroses: a study of 75 patients.

BACKGROUND: Clear cell sarcoma (CCS) of tendons and aponeuroses (malignant melanoma of soft parts) is a rare melanocytic soft tissue sarcoma. The objective of this study was to determine the clinical features, prognostic factors, and optimal treatment policy for patients with this rare disease. METHODS: Seventy-five consecutive patients with histologically confirmed CCS who received treatment between 1980 and 2004 were analyzed retrospectively. RESULTS: There were 41 men and 34 women, and the median age was 36 years. Sixty-five tumors were located in the extremities, and 10 tumors were located in the trunk. The median tumor size was 4 cm. Seventy-one patients underwent surgical excision, and 56 patients received chemotherapy. Sixteen patients developed local recurrences, and 52 patients developed metastasis. The overall patient survival rates was 47% at 5 years and 36% at 10 years. Univariate analysis showed that sex (P = .018), tumor size (P = .001), tumor depth (P = .002), TNM classification (P = .001), and surgical margin (P = .042) were significant prognostic factors. Among the 52 patients who presented with localized disease, sex (P = .023), tumor size (P = .002), tumor depth (P = .011), TNM classification (P = .004), and chemotherapy (P = .032) were identified as significant prognostic factors. Multivariate analysis showed that tumor size remained an independent prognostic factor in both groups. CONCLUSIONS: The current results supported the contention that early diagnosis and initial wide excision are essential for a favorable outcome of CCS. The role of chemotherapy for CCS should be investigated further.

Adult↗
PubMed2006

Preliminary results of phase I trial of oral uracil/tegafur (UFT), leucovorin plus irinotecan and radiation therapy for patients with locally recurrent rectal cancer.

BACKGROUND: Surgical attempts for locally recurrent rectal cancer often fail due to local re-recurrence and distant metastasis. Preoperative chemoradiation may enhance better local control and survival. The aim of this study was to assess the safety of oral uracil and tegafur (UFT) plus leucovorin (LV), and irinotecan combined with radiation and determine the maximum-tolerated dose (MTD) and dose limiting toxicity (DLT) of the triple drug regimen. PATIENTS AND METHODS: Patients with locally recurrent rectal cancer received escalating doses of irinotecan on days 1, 8, 15, and 22 (starting at 30 mg/m2, with 10 mg increments between consecutive cohorts) and fixed doses of UFT (300 mg/m2) plus LV (75 mg/day) on days 3 to 7, 10 to 14, 17 to 21, and 24 to 28. Radiation was given 5 days per week totaling 40 to 50 Gy (2Gy/day). RESULTS: Six patients were treated at the starting dose, and 2 received the full scheduled chemoradiotherapy. The other 4 patients had grade 3 diarrhea and diarrhea was the DLT. One patient had partial response and he had subsequently radical surgical resection. Median progression free survival for local recurrence was 320 days. CONCLUSION: Irinotecan plus UFT/LV with concomitant radiotherapy in patients with locally recurrent rectal cancer was not feasible due to diarrhea in this setting. Modification of the treatment is needed.

Journal Article↗
PubMed2006

Bone morphogenetic protein-2 promotes the haptotactic migration of murine osteoblastic and osteosarcoma cells by enhancing incorporation of integrin beta1 into lipid rafts.

Cell migration is essential for both organogenesis and tumor progression. Bone morphogenetic proteins (BMPs) are reported to be critical for not only bone formation but also tumor invasion. Here, we found that treatment with recombinant human BMP-2 (rhBMP-2) enhanced the haptotactic response of murine osteoblastic MC3T3-E1 and osteosarcoma Dunn cells to various extracellular matrix (ECM) components, including fibronectin, type I collagen, and laminin-1. Function-blocking antibody against integrin alpha5beta1 partially inhibited haptotaxis to fibronectin, suggesting that the response was propagated via these integrins. rhBMP-2 slightly increased the expression level of integrin beta1, and enhanced the speed of cell spreading on fibronectin, focal adhesion formation and phosphorylation of focal adhesion kinase (FAK) at Tyr397. By means of sucrose gradient flotation, incorporation of integrin beta1 in fractions of detergent (CHAPS) resistant membrane was increased when the cells were treated with rhBMP-2. Further, treatment with methyl-beta-cyclodextrin to deplete membrane cholesterol abrogated the effect of rhBMP-2 on haptotaxis, and exogenously added cholesterol reversed this inhibitory effect. Collectively, these results provide insights into the mechanism by which BMP signaling enhances cell migration by modulating fibronectin-integrin beta1 signaling via cholesterol enriched membrane microdomains, lipid rafts.

3T3 Cells↗
PubMed2006

A novel type of EWS-CHOP fusion gene in myxoid liposarcoma.

The cytogenetic hallmark of myxoid type and round cell type liposarcoma consists of reciprocal translocation of t(12;16)(q13;p11) and t(12;22)(q13;q12), which results in fusion of TLS/FUS and CHOP, and EWS and CHOP, respectively. Nine structural variations of the TLS/FUS-CHOP chimeric transcript have been reported, however, only two types of EWS-CHOP have been described. We describe here a case of myxoid liposarcoma containing a novel EWS-CHOP chimeric transcript and identified the breakpoint occurring in intron 13 of EWS. Reverse transcription-polymerase chain reaction and direct sequence showed that exon 13 of EWS was in-frame fused to exon 2 of CHOP. Genomic analysis revealed that the breaks were located in intron 13 of EWS and intron 1 of CHOP.

Adult↗
PubMed2006

Prognostic significance of Wilms tumor gene (WT1) mRNA expression in soft tissue sarcoma.

BACKGROUND: There have been several recent reports that Wilms tumor gene (WT1) mRNA is overexpressed in many types of neoplasms, and those results suggested that WT1 has oncogenic properties. The objective of the current study was to evaluate the prognostic significance of WT1 mRNA expression in patients with soft tissue sarcoma. METHODS: Levels of WT1 mRNA expression were examined by quantitative, real-time reverse transcriptase-polymerase chain reaction analysis in frozen tissue samples from 52 patients with soft tissue sarcoma. Various clinicopathologic factors were analyzed along with the disease-specific survival rate for correlations with WT1 mRNA expression levels. RESULTS: The levels of WT1 mRNA expression in a variety of soft tissue sarcomas were significantly greater compared with the levels in normal soft tissue samples (P = .0212). No significant correlation was observed between the level of WT1 mRNA expression and clinicopathologic factors, including gender, age, primary tumor site, tumor depth, tumor size, histologic grade, and distant metastasis at initial presentation. The disease-specific survival rate for patients with high WT1 mRNA expression levels was found significantly poorer compared with the rate for patients with low WT1 mRNA expression levels (P = .0182). Moreover, multivariate analysis indicated that a high WT1 mRNA expression level was an independent, adverse prognostic factor for disease-specific survival (hazards ratio, 2.6; P = .0488). CONCLUSIONS: WT1 mRNA expression level can serve as a potent prognostic indicator in soft tissue sarcoma patients.

Base Sequence↗
PubMed2006

Prognostic significance of activated AKT expression in soft-tissue sarcoma.

PURPOSE: AKT is a serine/threonine kinase which is important in tumorigenesis. Several molecules involved in AKT pathway are dysregulated in various kinds of human cancers. PATIENTS AND METHODS: Ninety-three patients (53 males and 40 females), ages ranging from 19 to 77 years (median, 57 years), with localized soft-tissue sarcomas arising in the trunk and extremities, were analyzed. Immunoperoxidase procedure (avidin-biotin complex method) was done on paraffin-embedded sections with anti-phosphorylated AKT (Thr308), anti-phosphorylated p44/42 extracellular signal-regulated kinase 1 and 2 (ERK1/2) (Thr202/Tyr204), anti-phosphorylated forkhead in rhabdomyosarcoma (FKHR) (Ser256), and anti-Ki 67 antibodies. Expression levels of phosphorylated AKT (p-AKT), phosphorylated ERK1/2 (p-ERK1/2), and phosphorylated FKHR (p-FKHR) were categorized as either weaker (level 1) or equal to or stronger (level 2) compared with those in the endothelial cells of the same specimens. Percentage of cells showing intranuclear staining with Ki-67 was shown as the Ki-67 labeling index (LI). Cases were divided into two groups: level 1, Ki-67 LI < 20%; level 2, Ki-67 LI > or = 20%. RESULTS: Twenty-six (28.0%), 6 (6.5%), and 46 (44.1%) of the tumors showed level 2 expression for p-AKT, p-ERK1/2, and Ki-67 LI, respectively. Tumors with level 2 p-AKT expression showed a higher ratio of level 2 p-FKHR expression (P < 0.01). Multivariate analysis revealed p-AKT expression and Ki-67 LI to be independent prognosticators for overall survival, and p-AKT expression for disease-free survival. CONCLUSION: p-AKT expression level is a significant prognosticator in soft-tissue sarcoma.

Adult↗
PubMed2006

A phase I/II trial of a WT1 (Wilms' tumor gene) peptide vaccine in patients with solid malignancy: safety assessment based on the phase I data.

OBJECTIVE: We conducted a phase I study to investigate the safety of a weekly WT1 tumor vaccine therapy in patients with solid tumors that had been refractory to all other anti-cancer therapies. METHODS: Skin-test-negative patients were intradermally injected weekly for 12 weeks with 3.0 mg of an HLA-A*2402-restricted modified 9-mer WT1 peptide emulsified in Montanide ISA51 adjuvant. We estimated the Bayesian posterior probability of the occurrence of grade 3 or 4 toxicity when receiving the weekly WT1 vaccination. This analysis provided the basis for making a decision to terminate the phase I study and switch to phase II. Moreover, we performed an exploratory assessment of the anti-tumor effects of WT1 treatment. RESULTS: Ten patients received 114 vaccinations with WT1 on a weekly schedule. No grade 3 or 4 toxicities were observed. Based on the Bayesian approach, it was highly likely that the probability of grade 3 or 4 toxicity was below 20% (the posterior probability = 0.914). Fifteen grade 2 and two grade 1 toxicities were observed; all of these incidents, however, were determined by the Independent Data and Safety Monitoring Committee to be unrelated to the WT1 treatment. One patient exhibited a partial response; five additional patients had stable disease while receiving weekly WT1 treatment. CONCLUSION: This paper confirms that the potential toxicities of the treatment schedule of weekly WT1 vaccination are acceptable and suggested a potential anti-tumor effect. Consequently, we validated the decision to continue to the phase II trial.

Adolescent↗
PubMed2006

Long-term follow-up after limb salvage in skeletally immature children with a primary malignant tumor of the distal end of the femur.

BACKGROUND: Skeletally immature children with a primary malignant tumor in the distal end of the femur are candidates for limb-salvage surgery; however, functional impairment due to subsequent limb-length discrepancy must be considered. Our aim was to evaluate the long-term clinical outcome of limb salvage in patients with a sarcoma of the distal end of the femur who were eleven years old or less, focusing on limb-length discrepancy and complications. METHODS: The cases of forty children were retrospectively reviewed in a multicenter study based on the responses to a questionnaire. Twenty-eight patients had had endoprosthetic reconstruction, and twelve had had biological reconstruction. Functional evaluation was based on the Musculoskeletal Tumor Society scoring system, with numerical values from 0 to 5 points assigned for each of the following six categories: pain, function, emotional acceptance, use of supports, walking ability, and gait. These values were added, and the functional score was presented as a percentage of the maximum possible score. Limb-length discrepancy was measured with orthoroentgenograms. Complications and their treatment were analyzed. Patient survival and the survival of the reconstructions were analyzed with use of the Kaplan-Meier method. RESULTS: Seven patients died and thirty-three remained alive, for a survival rate of 82% at ten years postoperatively. For the surviving patients, the mean follow-up periods (and standard deviations) were similar for the twenty-two who had endoprosthetic reconstruction (13.2 +/- 3.9 years) and the eleven who had biological reconstruction (10.4 +/- 4.4 years). All patients had reached skeletal maturity. The mean final functional score was 74% +/- 18% in the endoprosthetic reconstruction group and 68% +/- 17% in the biological reconstruction group (p = 0.37). For the nineteen patients who underwent limb-lengthening, the mean functional score increased significantly from 65% +/- 21% before the procedure to 81% +/- 11% after the lengthening (p = 0.0016). There were five early and twenty-eight late complications. In the endoprosthetic reconstruction group, the most frequent complications were deep infection and aseptic loosening. In the biological reconstruction group, the most frequent complications were implant breakage and nonunion. Revision surgeries were required in seventeen patients, including five who had an amputation. The rate of survival of the endoprosthetic reconstructions was 77% at five years and 51% at ten years postoperatively, whereas the rate of survival of the biological reconstructions was 46% at both five and ten years postoperatively. CONCLUSIONS: Endoprosthetic or biological reconstructions as limb salvage provided good functional outcome in skeletally immature children with a malignant bone tumor of the distal aspect of the femur despite a high rate of revisions and limb-lengthening procedures.

Adolescent↗
PubMed2005

False positive 18F-FDG PET in an ischial chondroblastoma; an analysis of glucose transporter 1 and hexokinase II expression.

We report a rare case of chondroblastoma arising from the ischium which showed an increased (18)F-FDG uptake. Chondroblastoma is an uncommon lesion and usually involves the epiphysis of long bones. However, in this case, the tumor appeared as a well-defined osteolytic lesion in the ischium on radiographs. MR imaging demonstrated two components in the tumor: a solid one and a multilobular cystic component. (18)F-FDG PET imaging revealed an increased uptake in the ischium. The (18)F-FDG uptake resembled the results observed in malignant bone tumors. A histological diagnosis of chondroblastoma was obtained from tissue of an open biopsy. An immunohistochemical analysis demonstrated weak expression of both Glut-1 and HK-II. These findings suggest that Glut-1 and HK-II expression are not strongly related to FDG uptake in chondroblastoma.

Adult↗
PubMed2005

FDG-PET imaging for chronic expanding hematoma in pelvis with massive bone destruction.

Chronic expanding hematoma is a rare presentation of a hematoma characterized by a persistent increase in size for more than a month after the initial hemorrhage. We present a 65-year-old man with a chronic expanding hematoma in his ilium who was receiving anticoagulant treatment. The patient had a delayed manifestation of a femoral neuropathy with massive bone destruction. 2-Deoxy-[18F]fluoro-D: -glucose (FDG) positron emission tomography (PET) imaging revealed an increased uptake in the rim of the mass in images acquired 1 h after FDG injection. FDG-PET scans were performed using a dedicated PET scanner (HeadtomeV/SET2400 W, Shimadzu, Kyoto, Japan), and the PET data for the most metabolically active region of interest (ROI) were analyzed. The maximum standardized uptake value (SUVmax) was set to a cut-off point of 3.0 to distinguish between benign and malignant lesions. The SUVmax of the patient's lesion was 3.10, suggesting a malignant lesion. The characteristics of FDG-PET images of chronic expanding hematomas, including the uptake of FDG in the peripheral rim of the mass as a result of inflammation, should be recognized as a potential interpretive pitfall in mimicking a sarcoma.

Aged↗
PubMed2005

Quantification of SSX mRNA expression in human bone and soft tissue tumors using nucleic acid sequence-based amplification.

The SSX family proteins have been considered new members of the cancer/testis antigens because of the restricted expression in testis among normal tissues and the activation in a wide range of cancers. Thus, they would be potential molecular targets for immunotherapeutic strategies. We have developed a competitive nucleic acid sequence-based amplification (NASBA) assay to analyze SSX mRNA expression in 211 bone and soft tissue tumors. The copy numbers of SSX mRNA per mug of total RNA in tumor tissues were widely distributed, ranging logarithmically from 0.6 to 6.6. We found that malignant tumors showed significantly higher expression of SSX mRNA than benign tumors (P < 0.0001). Further, SSX mRNA expression in stage III tumors was significantly higher than that in stage I or II tumors (P < 0.005). This NASBA assay was also more sensitive compared to immunohistochemistry using newly affinity-purified polyclonal antibody against SSX. Collectively, these results suggest that the SSX quantitative NASBA assay could provide useful information to select eligible patients for SSX-specific cancer vaccines.

Adolescent↗
PubMed2005

Prognostic relevance of clinical symptoms in patients with spinal metastases.

UNLABELLED: Medical and surgical advances allow surgical treatment of many patients with spinal metastases. Although emerging surgical techniques facilitate stabilization of the collapsed spine, surgical candidates should be carefully selected. However, the lack of confirmed criteria to determine survival of these patients makes selection for surgery difficult. Clinical symptoms have been considered possible factors associated with prognosis, but their relevance has not been confirmed because of inadequate power for proper statistical analysis. We retrospectively reviewed 165 patients who had surgery for spinal metastases from various cancers. Clinical symptoms including pain, paresis, and walking status were recorded. Multivariate analysis indicated that the histologic type of the primary tumor was the strongest prognostic factor, followed by preoperative paresis and pain. Myeloma, thyroid cancer, renal cell cancer, breast cancer, and prostate cancer had better prognoses than other kinds of cancer. Patients without paresis before surgery had a better prognosis than patients with paresis, and patients with no pain before surgery had a better prognosis than those with pain. Preoperative walking status was not an independent prognostic factor. LEVEL OF EVIDENCE: Therapeutic study, Level IV (case series--no, or historical control group). See the Guidelines for Authors for a complete description of levels of evidence.

Evidence-Based Medicine↗
PubMed2004

Peripheral nerve schwannoma: two cases exhibiting increased FDG uptake in early and delayed PET imaging.

We present two cases of peripheral nerve schwannoma which showed an increased accumulation of 2-deoxy-[(18)F] fluoro-D-glucose (FDG) in the tumors on positron emission tomography (PET) imaging acquired at both 1 h (early phase) and 2 h (delayed phase) after FDG injection. FDG-PET scans were performed with a dedicated PET scanner (HeadtomeV/ SET2400 W, Shimadzu, Kyoto, Japan) and the PET data analyzed the most metabolically active region of interest (ROI). We set the maximum standardized uptake value (SUV max) with a cut-off point of 3.0 to distinguish benign and malignant lesions. Although the mechanism responsible for the increased FDG uptake in benign schwannomas remains unknown, we discuss our findings in the context of tumor cellularity and briefly review other studies on the subject.

Adult↗
PubMed2004

Bone morphogenetic proteins in bone tumors.

Bone morphogenetic proteins (BMPs), inducers of ectopic bone formation in vivo, are present in a number of osteosarcomas. BMPs are responsible for reactive bone formation, including periosteal reactions by normal osteoblasts, rather than production of tumorous osteoid by tumor cells. Osteosarcomas producing BMPs contain less-differentiated mesenchymal cells, resulting in a poorer prognosis for those patients. BMPs are also expressed in malignant fibrous histiocytomas (MFHs) of bone and dedifferentiated chondrosarcomas exhibiting undifferentiated features. However, BMPs in MFH do not show any osteoinductive activity in vivo, suggesting that those BMPs may be inactive forms and have additional functions unrelated to bone formation. Among benign bone tumors, BMPs are expressed in osteoid osteomas or osteoblastomas and effect reactive bone formation such as a surrounding sclerosis. BMPs and a BMP receptor (BMPRIB) are also detected in the cartilage cap in osteochondroma, suggesting that BMP signaling via BMPRIB might be involved in the pathogenesis of osteochondroma. Clinically, BMPs have utility as diagnostic and prognostic markers for characterizing the stage of differentiation of mesenchymal cells and mesenchymal tumors, and they may be of value in predicting the prognosis of sarcoma patients. This article reviews the accumulated information on BMPs in bone tumors, including the most recent findings, and discusses the biological and clinical significance of BMPs in bone tumors.

Animals↗
PubMed2004

Postradiation soft tissue sarcoma: a multiinstitutional analysis of 14 cases in Japan.

Radiation therapy (RT) is commonly used to treat malignant tumors, but it leads to side effects and complications. Postradiation sarcomas developing from a previously irradiated area are especially vicious to deal with, though their occurrence is rare. This article focuses on the clinical manifestations, pathological characteristics, and therapeutic effects concerning postradiation soft tissue sarcomas (PRSTSs). A series of 14 PRSTSs treated between 1979 and 2000 in five hospitals in Japan were analyzed. Their histological types were malignant fibrous histiocytoma (eight cases), extraskeletal osteosarcoma (four cases), fibrosarcoma (one case), and leiomyosarcoma (one case). The primary diagnoses, RT history, latent period, and outcome of treatment were studied retrospectively. The original tumors included uterine cancer (seven cases), breast cancer (four cases), synovial sarcoma (one case), squamous cell carcinoma (one case), and Hodgkin's disease (one case). There were 13 women and 1 man, with ages ranging from 23 to 77 years (mean 58 years) at the time of the appearance of the PRSTS. RT doses ranged from 48 to 91 Gy (mean 62 Gy). The latent period from RT to the occurrence of the PRSTS varied from 4 to 27 years (mean 12.6 years). Altogether, 4 of 13 patients (31%) had recurrence of the sarcoma after resection. Of the 10 patients whose tumors were removed with a wide margin, one had a local recurrence; 3 cases were performed with a marginal margin and all 3 had a local recurrence. One of three who underwent RT and one of five who underwent chemotherapy (CT) responded. Of the 14 patients, 6 (42.9 %) survived continuously disease free, 2 (14.3%) died from other causes, 2 (14.3%) has an unknown outcome, and 4 (28.6 %) died of the disease during the follow-up period of 16-36 months (mean 24 months). The deaths due to other causes included an esophageal cancer and a wound infection. The prognosis of the PRSTS patients was not poor if the tumor could be removed with a wide surgical margin. Because adjuvant therapies including RT and CT had a poor effect on PRSTSs, the primary treatment of PRSTSs should be radical resection with a wide margin.

Adult↗
PubMed2004

Interleukin-6/soluble interleukin-6 receptor signaling attenuates proliferation and invasion, and induces morphological changes of a newly established pleomorphic malignant fibrous histiocytoma cell line.

Pleomorphic malignant fibrous histiocytoma (MFH) is occasionally associated with inflammatory paraneoplastic syndrome (PNS). Recently, we reported that interleukin (IL)-6, one of the candidate cytokines, which induces such systemic inflammatory reaction, may be a tumor-associated factor involved in the pathogenesis and its clinical manifestations of MFH. In the local microenvironment, tumor-induced inflammatory reaction may play a role favoring tumor progression. To clarify the biological relevance of IL-6 in MFH, we established a human MFH cell line, named MIPS-2, derived from a resected specimen of a patient presenting with PNS. In this patient, the serum IL-6 level ran parallel to the disease course: elevated serum IL-6 concentration normalized immediately after radical surgery, and re-elevation occurred on tumor recurrence. MIPS-2 presented pleomorphic appearance, severe nuclear abnormalities with prominent nucleoli, and tumorigenesis in nude mice. MIPS-2 expressed IL-6, IL-6 receptor (IL-6R), and glycoprotein 130 (gp130) but lacked the soluble form of IL-6R (sIL-6R), as determined by flow cytometry and reverse transcriptase-polymerase chain reaction analyses. Stimulation of MIPS-2 with IL-6 combined with exogenous sIL-6R induced phosphorylation of both signal transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinase (MAPK), decreased cell proliferation, attenuated invasion, and induced morphological changes. Collectively, these data suggested that the IL-6/sIL-6R signaling pathway plays a pivotal role for proliferation, invasion, and morphology of MFH via STAT3 and MAPK pathway as autocrine and/or paracrine manner, and proposed the therapeutic potential for the use of both anti-growth factor and proinflammatory cytokine-targeting strategies to combat devastating MFH.

Adult↗