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Biomedical subjects

Tadashi Hasegawa

Publications and source records attributed to Tadashi Hasegawa.

At least 19 recordsLinked to original sources
PubMed2007

Dysadherin expression as a significant prognostic factor and as a determinant of histologic features in synovial sarcoma: special reference to its inverse relationship with E-cadherin expression.

Dysadherin is a cancer-associated cell membrane glycoprotein, which down-regulates E-cadherin and promotes metastasis. Synovial sarcoma is a very rare mesenchymal tumor that exhibits an epithelial profile. To confirm the diagnosis of synovial sarcoma, we evaluated several immunohistochemical markers, or detected SYT-SSX fusion gene transcript. We studied the clinicopathologic features in 92 synovial sarcoma patients and also assessed the immunohistochemical expression of dysadherin and E-cadherin to examine their possible association with histologic subtype and biologic behavior. Moreover, among 30 patients, for whom frozen materials were available, dysadherin mRNA expression was examined by reverse transcription-polymerase chain reaction and real-time quantitative reverse transcription-polymerase chain reaction analysis. Dysadherin-positive expression was significantly correlated with E-cadherin-reduced expression (P=0.0004). Dysadherin-positive immunostaining was diffusely observed in the membranes of tumor cells in 30/68 (44%) patients with monophasic fibrous type and in 1/2 (50%) patients with poorly differentiated type. However, in biphasic tumors, dysadherin expression in the fibrous component was not diffusely observed, but often sporadically or focally observed [20/22 (91%) patients]. In addition, dysadherin mRNA expression in monophasic fibrous type was significantly higher than in biphasic type (P=0.0079). Synovial sarcoma patients with dysadherin expression survived for a significantly shorter time than those without dysadherin expression (P=0.0006). Patients with combined dysadherin-positive expression and E-cadherin-reduced expression had a significantly worse prognosis than those with other combinations of dysadherin and E-cadherin expression (P=0.0007). SYT-SSX fusion gene transcript was detected in 39 patients. In our series, SYT-SSX fusion type was found to have no correlation with histologic subtype, prognosis, or dysadherin expression. In multivariate analysis, dysadherin immunopositivity (P=0.0411) was an independent adverse prognostic factor, in addition to a high MIB-1 labeling index (> or =10%). We conclude that E-cadherin dysfunction by dysadherin is associated with reduced E-cadherin expression and morphologic change from epithelioid to spindle phenotype. Dysadherin expression is considered to be one of the determinants of histologic subtype in synovial sarcoma. Moreover, dysadherin expression is an excellent and independent prognostic indicator.

Adult↗
PubMed2007

Clinical relevance of pathological grades of malignant peripheral nerve sheath tumor: a multi-institution TMTS study of 56 cases in Northern Japan.

BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) is a relatively rare soft tissue tumor, and its clinical relevance of pathological grades remains obscure. METHODS: Fifty-six cases of MPNST identified from the files of seven oncology centers of the Tohoku Musculoskeletal Tumor Society (TMTS) and National Cancer Center were analyzed for histologic grades, demographics, treatments, and prognostic factors. The average follow-up period was 41 months. RESULTS: Twenty-two men and 34 women with a mean age of 45 years were involved. Forty-four (78.6%) of 56 tumors were in the lower extremity or trunk. Fifty tumors (89%) were classified as high grade, and the remaining six as low grade. Twenty-one (39.6%) of 53 patients who underwent tumor excision developed local recurrences. An axial site and inadequate surgical margin were defined as risk factors for local recurrence. The overall survival rates of the 56 patients were 55.1% at 3 years and 43.3% at 5 years. Univariate analysis of the 56 patients revealed large-sized tumors, metastasis at presentation, and histologically high grade were significantly associated with poor prognosis. Multivariate analysis revealed a large tumor and metastasis at presentation to be independent prognostic factors. CONCLUSIONS: The current study involving 56 patients with MPNST showed the aggressive clinical behavior of the tumor. Large-sized tumors, metastasis at presentation, and high histological grade were related to poor prognosis on univariate analysis, but independency of histological grade was still obscure. In the treatment for a large and high-grade MPNST, an alternative strategy should be further considered.

Adolescent↗
PubMed2006

The SYT-SSX fusion protein down-regulates the cell proliferation regulator COM1 in t(x;18) synovial sarcoma.

Chromosomal translocations are frequently associated with soft-tissue sarcomas. Fusion proteins generated by such translocations often play critical roles in tumorigenesis. Therefore, it is important to understand the function of the fusion protein to develop therapeutic interventions. The t(X;18)(p11.2;q11.2) translocation found in synovial sarcomas results in a fusion between the SYT gene on chromosome 18 and an SSX gene on the X chromosome. Although SYT-SSX fusion proteins appear to trigger synovial sarcoma development, little is known about the downstream targets of SYT-SSX. We found that the SYT-SSX fusion protein produces a dominant-negative function for SYT, which is a transcriptional coactivator. We then analyzed the gene expression profiles of SYT-SSX1-expressing HeLa cells using oligonucleotide microarrays and found that the SYT-SSX1 fusion protein directly down-regulated the expression of COM1, a regulator of cell proliferation. COM1 was found to be expressed at relatively low levels in synovial sarcoma tissues and cell lines. We then investigated the impact of conditional COM1 expression in the synovial sarcoma cell line. Increased COM1 expression resulted in induced apoptosis and in reduced cell growth and colony formation activity. Our results suggested that restoration of COM1 expression may be of therapeutic benefit in synovial sarcoma.

Apoptosis↗
PubMed2006

Dispersion and separation of small-diameter single-walled carbon nanotubes.

The dispersion of small-diameter single-walled carbon nanotubes (SWNTs) produced by the CoMoCAT method in tetrahydrofuran (THF) with the use of amine was studied. The absorption, photoluminescence, and Raman spectroscopies showed that the dispersion and centrifugation process leads to an effective separation of metallic SWNTs from semiconducting SWNTs. Since this method is simple and convenient, it is highly applicable to an industrial utilization for widespread applications of SWNTs.

Journal Article↗
PubMed2006

Cancer diagnosis marker extraction for soft tissue sarcomas based on gene expression profiling data by using projective adaptive resonance theory (PART) filtering method.

BACKGROUND: Recent advances in genome technologies have provided an excellent opportunity to determine the complete biological characteristics of neoplastic tissues, resulting in improved diagnosis and selection of treatment. To accomplish this objective, it is important to establish a sophisticated algorithm that can deal with large quantities of data such as gene expression profiles obtained by DNA microarray analysis. RESULTS: Previously, we developed the projective adaptive resonance theory (PART) filtering method as a gene filtering method. This is one of the clustering methods that can select specific genes for each subtype. In this study, we applied the PART filtering method to analyze microarray data that were obtained from soft tissue sarcoma (STS) patients for the extraction of subtype-specific genes. The performance of the filtering method was evaluated by comparison with other widely used methods, such as signal-to-noise, significance analysis of microarrays, and nearest shrunken centroids. In addition, various combinations of filtering and modeling methods were used to extract essential subtype-specific genes. The combination of the PART filtering method and boosting--the PART-BFCS method--showed the highest accuracy. Seven genes among the 15 genes that are frequently selected by this method--MIF, CYFIP2, HSPCB, TIMP3, LDHA, ABR, and RGS3--are known prognostic marker genes for other tumors. These genes are candidate marker genes for the diagnosis of STS. Correlation analysis was performed to extract marker genes that were not selected by PART-BFCS. Sixteen genes among those extracted are also known prognostic marker genes for other tumors, and they could be candidate marker genes for the diagnosis of STS. CONCLUSION: The procedure that consisted of two steps, such as the PART-BFCS and the correlation analysis, was proposed. The results suggest that novel diagnostic and therapeutic targets for STS can be extracted by a procedure that includes the PART filtering method.

Algorithms↗
PubMed2006

Correlation of p53 and MIB-1 expression with both the systemic recurrence and survival in cases of phyllodes tumors of the breast.

Phyllodes tumors are rare primary tumors of the breast. The study aimed at evaluating the immunohistochemical features of phyllodes tumors of the breast that may be useful for predicting the clinical outcome. We examined the immunohistochemical expression of the epidermal growth factor receptor (EGFR), HER2/neu, CD117/c-kit, p53, and MIB-1, and analyzed correlations between the immunohistochemical findings and the clinical outcome. The study included 41 patients with phyllodes tumor (20 benign, 5 borderline, and 16 malignant). Systemic recurrence occurred in 9 patients. The 2-year survival rate was 84%, and the 2-year recurrence-free survival rate was 77%. Six patients developed systemic recurrence within the first year after surgery. None of the phyllodes tumors was positive for HER2/neu or CD117/c-kit. Positive staining for p53 was seen in 10 phyllodes tumors (24%), and the median MIB-1 index was 10%. Both p53 expression and the MIB-1 index, but not the expression status of EGFR, were significantly correlated with the recurrence-free and overall survival. p53 expression status and MIB-1 index may be significant prognostic factors in patients with phyllodes tumors, and careful postoperative follow-up may be important in those cases showing positive expression of p53 and/or MIB-1 index.

Adult↗
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

The value of MDM2 and CDK4 amplification levels using real-time polymerase chain reaction for the differential diagnosis of liposarcomas and their histologic mimickers.

Atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) and dedifferentiated liposarcoma (DDL) are reported to have murine double-minute type 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) amplification as a characteristic genetic alteration. To evaluate the diagnostic utility of this gene abnormality, we analyzed 19 liposarcomas, 21 malignant fibrous histiocytomas, 3 leiomyosarcomas, 5 malignant peripheral nerve sheath tumors, 23 lipomas, and 28 nonneoplastic fat tissues using real-time polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH). In real-time PCR, all ALT/WDLs and DDLs had both MDM2 and CDK4 amplifications. The amplification levels in ALT/WDLs and DDLs were significantly higher than those in the other sarcomas, lipomas, and nonneoplastic fat tissues (P < .05); however, those in the other sarcomas and lipomas were not significantly higher than those in nonneoplastic tissues. In FISH, all ALT/WDLs and DDLs had both MDM2 and CDK4 amplifications, and all of the myxoid/round cell liposarcomas, leiomyosarcomas, malignant peripheral nerve sheath tumors, and all but one of the malignant fibrous histiocytomas did not have the amplifications. In this study, MDM2 and CDK4 amplifications were confirmed in ALT/WDLs and DDLs, and the amplification levels were significantly higher than those in the other tumors. An analysis of MDM2 and CDK4 amplification using real-time PCR, as well as FISH, is useful for the differential diagnosis of liposarcomas and their histologic mimickers.

Adipose Tissue↗
PubMed2006

Utility of immunohistochemical analysis for cyclo-oxygenase 2 in the differential diagnosis of osteoblastoma and osteosarcoma.

AIMS: To study the immunoexpression of cyclo-oxygenase (COX) 2 in osteoblastomas (OBs) and osteosarcomas (OSs), and to assess the utility of immunohistochemical analysis for COX 2 in the differential diagnosis of the two tumour forms. METHODS: The immunohistochemical features of COX 2 were studied in 11 OBs and 30 OSs, including 26 high-grade OSs (16 osteoblastic, 7 chondroblastic, and 3 fibroblastic) and 4 low-grade OSs. RESULTS: Tumour cells from all 11 OBs unequivocally showed diffuse, intense and cytoplasmic immunoreactivity for COX 2. Strong cytoplasmic expression of COX 2 was observed in 5 of 26 (19%) high-grade OSs, all chondroblastic. In one osteoblastic-type OS, COX 2 was expressed in the chondroblastic component, but this tumour was considered to be COX 2 negative. No COX 2 expression was noted in atypical osteoblastic cells. Staining in the four low-grade OSs was negative. CONCLUSION: The results of immunohistochemical analysis of COX 2 suggest that in addition to the routine histopathological evaluation, COX 2 is a valuable diagnostic marker in the distinction between OB and OS.

Adolescent↗
PubMed2006

Disease activity and 18F-FDG uptake in organising pneumonia: semi-quantitative evaluation using computed tomography and positron emission tomography.

PURPOSE: The present study was conducted to evaluate whether( 18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in combination with computed tomography (CT) reflects disease activity in patients with organising pneumonia. METHODS: Eighty-eight subjects who were normal (n=66) or who had proven organising pneumonia (n=22) underwent FDG-PET and CT imaging. The subjects included 55 men and 33 women, ranging in age from 24 to 63 years (mean 47 years). PET and CT data sets were digitally fused using a conformational PET/CT fusion algorithm. All scans were evaluated independently by two chest radiologists who were unaware of other clinical data. The visual score, maximal and mean standardised uptake value (SUV), and maximal and mean lesion-to-normal tissue ratio (LNR) were calculated. The imaging results were compared with the laboratory and pulmonary function test results. The inflammatory cells in the lesions were quantified immunohistochemically. RESULTS: The visual score, maximal and mean SUV, and maximal and mean LNR of the patients with organising pneumonia were significantly higher than those of the normal subjects. The patients with air-space consolidation had a significantly higher SUV than those without air-space consolidation (mean+/-SD 3.08+/-0.39 vs 2.35+/-0.56; p<0.05). The number of CD45(+) cells was positively correlated with the maximal SUV (r=0.632, p<0.01) and the maximal LNR (r=0.453, p<0.05). The number of CD8(+) T lymphocytes also showed positive correlations with the maximal SUV (r=0.540, p<0.01) and the maximal LNR (r=0.547, p<0.01). CONCLUSION: Patients with organising pneumonia have an enhanced FDG accumulation which reflects the degree of disease activity.

Adult↗
PubMed2006

Glut-1 expression and enhanced glucose metabolism are associated with tumour grade in bone and soft tissue sarcomas: a prospective evaluation by [18F]fluorodeoxyglucose positron emission tomography.

PURPOSE: This study was conducted to investigate whether( 18)F-fluorodeoxyglucose (FDG) uptake, quantified by positron emission tomography (PET), correlates with histological variables including tumour grade, cell proliferation, cell cycle control integrity and glucose metabolism in patients with bone and soft tissue sarcomas. METHODS: Eighty-two patients clinically suspected of having a bone or soft tissue sarcoma underwent FDG PET within 1 week prior to operation and 63 patients (mean age 48 years, range 18-74 years) were enrolled in the complete analysis. We excluded 17 patients with pathologically confirmed benign tumours and two patients with uncontrolled diabetes or concomitant malignancy from data analysis. Maximum and average standardised uptake values (SUVs) of the primary lesion were compared with histological variables including tumour differentiation, the presence of necrosis, MIB-1 score, mitotic score, p53 overexpression, MIB-1 grade, mitotic grade and GLUT-1 expression. RESULTS: Significant correlations were found between maximal and mean SUVs and MIB-1 grade, mitotic grade, MIB-1 score, tumour differentiation and mitotic score. The mean and maximal SUVs were significantly higher in tumours with p53 overexpression than in those without p53 overexpression (p<0.0001). GLUT-1-positive tumours had significantly higher mean (6.5+/-4.2 vs 1.1+/-0.2, p=0.006) and maximal SUVs (8.8+/-5.4 vs 1.7+/-0.5, p=0.005) than the GLUT-1-negative tumours. GLUT-1 intensity correlated positively with both mean (r=0.500, p<0.0001) and maximal SUVs (r=0.509, p<0.0001). Mu ltiple linear regression analysis showed a significant correlation between maximal SUV and MIB-1 grade (p<0.0001). CONCLUSION: The enhanced glucose metabolism, as determined by SUV, is a strong index of tumour grade in bone and soft tissue sarcomas.

Adolescent↗
PubMed2006

Cyclooxygenase-2 overexpression associated with a poor prognosis in chondrosarcomas.

Recent studies have shown increased levels of cyclooxygenase (COX)-2 in various human malignancies, including some bone and soft tissue tumors, but little is known about the presence of COX-2 in chondrosarcomas. We performed immunohistochemical staining for COX-2 in 74 chondrosarcomas and compared the staining results with the characteristics and outcome of the patients. Thirty-seven men and 37 women between the ages of 14 and 81 years (median, 50 years) participated in the study. The tumors were located in the axial skeleton in 47 cases and in the long bones in 27 cases. The largest diameters of the tumors ranged from 2.7 to 32 cm (median, 8.0 cm). The immunohistochemistry findings revealed the overexpression of COX-2 in 16 (22%) of the 74 patients. Thirteen (41%) of 32 grade 2 and 2 (67%) of 3 grade 3 chondrosarcomas showed overexpression for COX-2, whereas only 1 (3%) of 39 grade 1 chondrosarcomas showed overexpression. Overexpression of COX-2 was significantly associated with histologic grade (P < .001) and a decreased disease-specific survival (P < .001). These findings suggest that COX-2 overexpression in chondrosarcoma is a negative prognostic factor that may be strongly associated with histologic grade.

Adolescent↗
PubMed2006

CT and MRI findings in KIT-weak or KIT-negative atypical gastrointestinal stromal tumors.

The large majority of gastrointestinal stromal tumors (GIST) can be diagnosed on the basis of KIT immunoreactivity. However, some atypical tumors show weak or negative KIT expression. We studied the imaging characteristics of atypical GIST, reviewing CT and MRI findings in ten patients (eight men, two women; mean age 59 years) with atypical GIST. Radiological studies were evaluated by two radiologists by consensus and included CT and MR imaging in all patients. Pathological diagnoses were made from surgery and confirmed by the polymerase-chain reaction (PCR) to amplify both exons of the c-kit gene and PDGFRA gene. The CT and MR examinations revealed a heterogeneous mass of the stomach containing cystic regions and soft tissue elements in all cases. All lesions were extraluminal masses and had an exophytic epicenter. On T1-weighted MR images soft tissue elements of the tumors were of homogeneously low- (n=3) or iso-signal intensity (n=7) compared with the liver parenchyma. On fast spin-echo T2-weighted MR images soft tissue elements of all tumors showed cystic regions of significantly high signal intensity interspersed with septumlike structures of low signal intensity. All lesions exhibited homogeneously (n=4) or heterogeneously (n=6) mild to moderate enhancement of soft tissue elements. Despite the relatively small number of patients CT and MRI findings of atypical GIST are a submucosal mass with soft tissue elements and cystic regions.

Aged↗
PubMed2006

Proteomic signatures corresponding to histological classification and grading of soft-tissue sarcomas.

We performed a global protein expression study on soft-tissue sarcoma in order to develop novel diagnostic biomarkers and allow molecular classification. 2-D difference gel electrophoresis was used to generate the global protein expression profiles of 80 soft-tissue sarcoma samples with seven different histological backgrounds. We found that 67 protein spots distinguished the subtypes of soft-tissue sarcoma. Hierarchical clustering with these 67 protein spots resulted in the grouping of all 80 sarcoma samples corresponding to the histological classification. We found that the expression pattern of tropomyosin isoforms was different in conventional and pleomorphic leiomyosarcomas. We also identified five proteins, including alpha-1-antitrypsin, alpha-actinin 1, HSP27, and elongation factor 2, that could differentiate between malignant fibrous histiocytomas and leiomyosarcomas in grade III into low-risk and high-risk groups, which differed significantly with respect to survival. These results establish proteomics as a powerful tool to develop novel biomarkers for diagnosis and molecular classification of soft-tissue sarcomas. Identification of proteins associated with survival in grade III sarcoma will allow delineation of a high-risk group that may benefit from adjuvant therapy and the exclusion of low-risk patients in whom additional therapies are unlikely to exhibit clinical benefit.

Biomarkers↗
PubMed2006

A case of ganglioneuroma presenting abnormal FDG uptake.

We report a case of ganglioneuroma with abnormal 18F-fluorodeoxyglucose (FDG) uptake. A 26-year-old woman presented to the hospital with a slowly growing abdominal tumor without symptoms. She was diagnosed with neuroblastoma in childhood and treated by surgery and chemotherapy. Computed tomography (CT) revealed huge retroperitoneal tumors and fused 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT image showed abnormal accumulation of FDG in tumors with maximal standardized uptake value of 2.02. Considering her past history, ganglioneuroma matured from neuroblastoma was considered, the most likely diagnosis. However, a second primary malignant tumor, such as malignant peripheral nerve sheath tumor arising in ganglioneuroma, could not be ruled out. Then, an excisional biopsy was performed and the diagnosis of mature ganglioneuroma was made. Pathological investigation may be needed to differentiate ganglioneuroma from other malignant tumors and, therefore, FDG-PET/CT findings can be helpful for biopsy planning.

Abdominal Neoplasms↗
PubMed2006

Diaphyseal medullary stenosis with pleomorphic malignant fibrous histiocytoma of the bone: 99mTc hydroxymethylenediphosphonate and 201Tl chloride scintigraphy findings.

Diaphyseal medullary stenosis (DMS) is an extremely rare hereditary bone dysplasia, which was first described by Arnold in 1973. DMS has a high incidence of pleomorphic malignant fibrous histiocytoma (MFH). In this paper, we report the imaging findings of DMS with pleomorphic MFH of the bone, mainly describing 99mTc hydroxymethylenediphosphonate (HMDP) and thallium-201 (201Tl) chloride scintigraphy findings. On 99mTc HMDP scintigraphy, focal increased uptake area of the right femur corresponded to the area of bone marrow invasion of the tumor and bone infarction. The mechanism of the uptake of 99mTc HMDP to the extraosseous lesion was not clear. On 201Tl chloride scintigraphy, the increased uptake of the periphery of the mass seemed to reflect the aggressiveness of invasion and the cellularity.

Adult↗
PubMed2006

Large benign rheumatoid nodules of the trunk in an elderly patient: radiologic appearance mimicking a soft-tissue sarcoma.

An 80-year-old woman without any evidence of rheumatoid arthritis presented with two large (maximum diameter: 6 cm and 7 cm), rapidly growing, rubbery nodules on the trunk. Although the clinical and radiological appearance suggested malignancy, the nodules were pathologically identical to rheumatoid nodules in rheumatoid arthritis, and the nodules regressed spontaneously. The final diagnosis was benign rheumatoid nodules. Recognition of this rare clinical entity is important to avoid unnecessary examination and treatment.

Aged, 80 and over↗