Biomedical subjects

Ikuo Kudawara

Publications and source records attributed to Ikuo Kudawara.

12 recordsLinked to original sources

PubMed2007

Analysis of germline and tumor mutations of p53 gene in familial occurrence of soft tissue sarcomas.

BACKGROUND: Familial soft tissue sarcomas are extremely rare. There is little information available on the clinical features and molecular findings of the hereditary occurrence of mesenchymal tumor. PATIENTS AND METHODS: A woman and her younger brother had malignant fibrous histiocytoma (pleomorphic type) and liposarcoma (pleomorphic type) in the lower limbs, respectively. Analysis of p53 mutations in exons 5-9 of the tumor and in germ-line was done. RESULTS: A guanine to adenine substitution occurred in CGC, codon 175 of exon 5 in p53 gene, to CAC in the tumor sample of Case 1. Likewise, a thymine to cytosine substitution occurred in TTT, codon 270 of exon 8 in p53 gene, to TCT in tumor sample of Case 2. Germline mutations were not seen in the either patients. CONCLUSIONS: Different missense mutations of p53 were detected in each tumor, however no germline mutations of p53 were found. The alteration of codon 175 in Case 1 is relatively common mutation. On the contrary, the mutation in codon 270 in Case 2 was extremely rare in cancers. Further molecular investigation is needed to understand the mechanism in familial occurrence of sarcomas.

Female↗

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↗

PubMed2004

Synovial chondromatosis of the acromioclavicular joint.

A 53-year-old woman presented with swelling of 3 years' duration on the right anterior chest wall. A radiograph showed coarse calcifications around the subclavicular region and erosion of the ipsilateral acromioclavicular joint. Computed tomography also showed calcifications in soft tissue. Magnetic resonance imaging revealed a tumor around the clavicle extending to the anterior aspect of chest wall, which had low signal intensity on T1-weighted imaging and high signal intensity on T2-weighted imaging. The histologic findings were of a hyaline cartilage-like mass consisting of mature chondrocytes and an extracellular matrix. The histologic diagnosis of synovial chondromatosis was made. The present case is unusual in respect of the location and size of the tumor.

Acromioclavicular Joint↗

PubMed2004

New cell lines with chondrocytic phenotypes from human chondrosarcoma.

In the present study, we investigated chondrocytic characterization for newly established human chondrosarcoma cell lines. A chondrosarcoma cell line, HCS-TG, was established by the implantation of grade-2 human chondrosarcoma into athymic mice. Cloning of HCS-TG cells from passage 17 was performed. After cell cloning, two clonal-cell lines (HCS-TG C3 and E2) with good proliferative activities were obtained. These cell lines in monolayer culture retained a polygonal morphology. Their doubling times were 68 h and 45 h, respectively. mRNA expressions of type-I, -II, -X, and -XI collagens and aggrecan core protein were detected on reverse-transcription polymerase chain reaction. Protein expression of type-II collagen was confirmed in each cell line using Western blotting. However, there was no expression of type-I collagen. Moreover, gelatin zymography revealed that both cell lines produced extracellular matrices with matrix metalloproteinases 2 and 9. The parental HCS-TG cells had tumorigenicity in athymic mice; however, C3 and E2 were not tumorigenic. New clonal-cell lines HCS-TG C3 and E2 derived from human chondrosarcoma are morphologically chondrocytic in serial monolayer cultures and express chondrocytic phenotypes.

Adult↗

PubMed2004

Synovial sarcoma after chemotherapy for osteosarcoma: a case report.

A 23-year-old man had eight cycles of adjuvant chemotherapy including doxorubicin, cisplatin, methotrexate, and ifosfamide and radical surgery for biopsy-proved osteosarcoma of the right fibular shaft. Two years after the initial diagnosis, he noticed a mass in the medial aspect of his right knee. Magnetic resonance imaging scans revealed a soft tissue tumor measuring 2 x 2 cm in the pericapsular region of the right knee. Histologically, this soft tissue tumor was composed of spindle cells with occasional atypical mitoses and without matrix formation. Immunohistochemically, the tumor cells were positive for vimentin, cytokeratin, and epithelial membrane antigen, and negative for alpha smooth muscle actin. A fusion gene, SYT-SSX was detected with reverse transcription-polymerase chain reaction. From the results, the secondary tumor was diagnosed as a synovial sarcoma. The current case of double sarcomas is rare. Both sarcomas were diagnosed accurately using immunohistochemical and molecular procedures. This case suggests a positive association between a second tumor and chemotherapy including intraarterial perfusion of doxorubicin.

Adult↗

PubMed2004

Bilateral achilles tendon ruptures in a patient with ochronosis: a case report.

We report the case of a 67-year-old man with ochronosis who had bilateral Achilles tendon ruptures. We reconstructed the Achilles tendon using pull-out wiring for the right side and an anchoring system for the left side, and reinforced the repair site using the peroneus brevis tendon for both sides. He could walk without a cane at 3 months postoperatively. Tendon ruptures in patients with ochronosis should be treated as pathologic ruptures because histologic examination reveals that both ends of the ruptured tendon and the insertion site at the calcaneus have extensive black pigment depositions where homogentisic acid and its metabolites have accumulated, and there are no normal collagen bundles present. Even if an Achilles tendon rupture is clinically diagnosed as an acute injury, the ruptured Achilles tendon should be primarily repaired and reinforced with autologous tissue because there are a few viable cells at the ruptured site, and because the tendon ruptures mainly at the insertion site of the calcaneus. Although this is a preliminary report, the short-term result is good and the reconstructed sites have showed no rerupture.

Achilles Tendon↗

PubMed2004

Prediction of response to neoadjuvant chemotherapy for osteosarcoma by gene-expression profiles.

To establish a method for predicting the response to chemotherapy for osteosarcoma (OS), we performed expression profile analysis using cDNA microarray consisting of 23,040 genes. Hierarchical clustering based on the expression profiles of 19 biopsy samples of OS demonstrated two major clusters, one of which consisted exclusively of typical OS, i.e. conventional central OS in long bone of patients in the second decade. A set of genes was identified to characterize this subgroup, some of which have previously indicated some relation to carcinogenesis. Thirteen of the 19 patients were treated with an identical protocol of chemotherapy containing doxorubicin, cis-platinum and ifosfamide, and histological examination of resected specimens after operation classified 6 cases as responder and 7 as non-responder. A comparison of expression profiles of these two groups identified 60 genes whose expression levels were likely to be correlated with the response to chemotherapy (P<0.008). A drug response scoring (DRS) system was developed based on the expression levels of these genes, which proved to be applicable to predict the response to chemotherapy irrespective for the subclassification of OS. The reliability of the DRS system was further confirmed by testing additional 5 OS cases. These results indicated that scoring system based on gene-expression profiles might be useful to predict the response to chemotherapy for OS.

Adolescent↗

PubMed2003

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↗

PubMed2002

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↗

PubMed1999

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↗

PubMedDate not supplied

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↗

PubMedDate not supplied

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↗