Biomedical subjects

Shuichi Matsuda

Publications and source records attributed to Shuichi Matsuda.

At least 37 records · Page 2Linked to original sources

PubMed2004

E-cadherin mutation and Snail overexpression as alternative mechanisms of E-cadherin inactivation in synovial sarcoma.

We have recently reported frequent E-cadherin gene mutations in synovial sarcoma (SS), suggesting mutational inactivation of E-cadherin as a potential mechanism of spindle cell morphology in SS, a spindle cell sarcoma that shows areas of glandular epithelial differentiaton in some cases (biphasic SS) and only pure spindle cell morphology in most cases (monophasic SS). However, the mechanism of downregulation of E-cadherin in SS remains unknown. To further address this issue, we analysed the mechanisms of E-cadherin silencing in 40 SS. Genetic and epigenetic changes in the E-cadherin gene, and the expression level of its transcriptional repressor Snail were examined by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP), methylation-specific PCR, and real-time quantitative PCR, respectively. Expression of E-cadherin was examined by RT-PCR and immunohistochemistry. We also examined ELF3, a transcription factor associated with epithelial differentiation in SS in a previous cDNA microarray, by RT-PCR. E-cadherin and ELF3 transcripts were detected, respectively, in 27/40 (67.5%) and in 25/40 (62.5%) of SS, and these epithelial-related genes were almost always coexpressed. Hypermethylation of the promoter of the E-cadherin gene was detected in five cases (12.5%) in SS; however, E-cadherin was silenced at mRNA level in only one of the five cases. E-cadherin missense mutations were observed in five cases (12.5%) of SS. In SS, all five cases with E-cadherin missense mutations had the SYT-SSX1 fusion and were monophasic tumors, suggesting a relationship between the SYT-SSX fusion type and E-cadherin missense mutation (P=0.07). E-cadherin mRNA expression in SS was associated with reduced Snail expression level (P=0.03). E-cadherin membranous expression was observed in 14/40 (35.0%) of SS, and was also correlated with SYT-SSX1 fusion type and biphasic histology. ELF3 was confirmed to be more highly expressed in biphasic than monophasic SS by real-time quantitative PCR. These results suggest that in SS the loss of E-cadherin expression occurs either by Snail trans-repression or by inactivating mutations. Thus, E-cadherin downregulation is associated with the loss or absence of glandular epithelial differentiation in certain SS.

Cadherins↗

PubMed2004

Anatomical analysis of the femoral condyle in normal and osteoarthritic knees.

It is important to understand anatomical feature of the distal femoral condyle for treatment of osteoarthritic knees. Detailed measurement of the femoral condyle geometry, however, has not been available in osteoarthritic knees including valgus deformity. This study evaluated femoral condyle geometry in 30 normal knees, 30 osteoarthritic knees with varus deformity, and 30 osteoarthritic knees with valgus deformity using radiographs and magnetic resonance imaging (MRI). In radiographic analysis in the coronal plane, the femoral joint angle (lateral angle between the femoral anatomic axis and a tangent to femoral condyles) was 83.3 degrees in the normal knees, 83.8 degrees in the varus knees, and 80.7 degrees in the valgus knees. In MRI analysis in the axial plane, the posterior condylar tangent showed 6.4 degrees of internal rotation relative to the transepicondylar axis in the normal knees, 6.1 degrees in the varus knees, and 11.5 degrees in the valgus knees. These results suggested that there was no hypoplasia of the medial condyle in the varus knees, but the lateral condyle in the valgus knees was severely distorted. Surgeons should take this deformity of the lateral femoral condyle into account when total knee arthroplasty is performed for a valgus knee.

Aged↗

PubMed2004

The oblique posterior femoral condylar radiographic view following total knee arthroplasty.

BACKGROUND: It is often difficult to evaluate the posterior aspects of the femoral condyles after total knee arthroplasty. We have developed an imaging technique involving the use of the oblique posterior condylar view for the evaluation of the posterior aspects of the femoral condyles. The purpose of the present study was to compare the efficacy of this view with that of the true-lateral view. METHODS: Three orthopaedic surgeons analyzed fifty-five sets of radiographs (consisting of oblique posterior condylar and true-lateral views) for patients who had undergone total knee arthroplasty. The accuracy and reproducibility of the oblique posterior condylar view for the detection of radiolucencies were compared with those of the true-lateral view. RESULTS: The oblique posterior condylar view was significantly better than the true-lateral view for the detection of radiolucencies of the posterior aspects of the femoral condyles (p < 0.0005). CONCLUSIONS: Radiographic analysis with use of the oblique posterior condylar view is technically easy and is accurate for the evaluation of radiolucencies of the posterior aspects of the femoral condyles after total knee arthroplasty.

Aged↗

PubMed2004

PTEN and other tumor suppressor gene mutations as secondary genetic alterations in synovial sarcoma.

Synovial sarcomas (SS) consistently show a characteristic chromosomal translocation, t(X;18)(p11;q11), which usually leads to the formation of 2 chimeric fusion transcripts, SYT-SSX1 and -SSX2. A recent multi-institutional retrospective study revealed that the SYT-SSX fusion type emerged as the only independent significant factor for overall survival in cases of SS. The aims of this study were; i). to investigate the frequency of PTEN gene alteration, ii). to evaluate whether the mutation status in various tumor suppressor genes (TSG) is responsible for the clinical and histologic heterogeneity in SS. Forty-nine cases of SS were examined for the presence of PTEN gene mutation by polymerase chain reaction - single-strand conformation polymorphism followed by DNA direct sequencing. The obtained data was combined with those of previously reported TSG mutations such as p53, adenomatous polyposis coli, and E-cadherin genes. Follow-up was available for 44 patients, and survival analysis was performed according to the mutation status of these TSG. PTEN mutations were detected in 7 cases (14.3%), and all of these were monophasic tumors. More than half of the mutations detected were located in exon 9, which has been shown to play a less important role in PTEN functioning, and the PTEN mutation was not associated with patients' prognosis. Mutations in these TSG other than silent mutations were detected in 20 out of 49 cases (40.8%), although the mutation status in TSG was not associated with overall survival rate in patients with SS. Secondary genetic alterations in these TSG seem to have a less important prognostic impact on patients with SS.

Adult↗

PubMed2003

Primitive neuroectodermal tumor and extraskeletal Ewing sarcoma arising primarily around the spinal column: report of four cases and a review of the literature.

STUDY DESIGN: Report of four cases and a review of the literature. OBJECTIVES: To study the clinical features and prognosis of primitive neuroectodermal tumor or extraskeletal Ewing sarcoma arising around the spinal column. SUMMARY OF BACKGROUND DATA: Primitive neuroectodermal tumor or extraskeletal Ewing sarcoma that originates around the spinal column is very rare, and its prognosis is very poor. METHODS: Four patients were diagnosed and underwent treatment. RESULTS: Although all the patients received high-dose chemotherapy with or without radiotherapy after surgery, three patients died of the disease. Only one patient who received en bloc resection of the tumor combined with multiagent chemotherapy followed by high-dose chemotherapy with peripheral blood stem cell transplantation remains alive and continues to be disease free. CONCLUSION: The prognosis of the patients with primitive neuroectodermal tumor or extraskeletal Ewing sarcoma around the spinal column is very poor. Multiagent chemotherapy combined with en bloc resection and radiation therapy is the preferred treatment for patients with primitive neuroectodermal tumor or extraskeletal Ewing sarcoma around the spinal column.

Adolescent↗

PubMed2003

PTEN/MMAC1 gene mutation is a rare event in soft tissue sarcomas without specific balanced translocations.

The tumor suppressor gene PTEN/MMAC1 was identified on chromosome 10q23.3, which is homozygously deleted in many human malignancies. The loss of chromosome 10q was also frequently reported in some types of soft tissue sarcomas. Our study was designed to investigate the frequency of PTEN/MMAC1 gene mutation and to evaluate the role of the PTEN/MMAC1 gene in the tumorigenesis of soft tissue sarcomas without specific balanced translocations. We analyzed 51 cases of soft tissue sarcomas without specific balanced translocations for PTEN/MMAC1 mutations by polymerase chain reaction-single strand conformation polymorphism and direct sequencing. Mutations in the PTEN/MMAC1 gene were found in only 2 cases (3.9%). Both tumors with PTEN/MMAC1 mutation were leiomyosarcomas arising from the retroperitoneum and inferior vena cava, respectively. Two of 3 leiomyosarcomas arising from the intra-abdominal cavity examined harbored mutations of this tumor suppressor gene. This result suggests that leiomyosarcomas derived from the intra-abdominal cavity might have different tumorigenesis from those of an extremity or the trunk, from the viewpoint of PTEN/MMAC1 mutation, although PTEN/MMAC1 gene mutations are rare event in these soft tissue sarcomas.

Base Sequence↗

PubMed2003

Changes in anteroposterior stability following total knee arthroplasty.

This study evaluated the changes in anteroposterior stability at flexion and extension following posterior cruciate ligament (PCL)-retaining and PCL-substituting total knee arthroplasty (TKA), in comparison with normal knees. Altogether, 29 knees of 24 patients underwent either PCL-retaining ( n = 19) or PCL-substituting ( n = 10) TKA. Anteroposterior displacement was measured with a KT-2000 arthrometer preoperatively, 1 month after surgery, and again an average of 3 years after surgery. Anteroposterior stability at flexion and extension did not change following PCL-retaining TKA and was not significantly different from that of normal subjects, whereas anteroposterior stability increased following PCL-substituting TKA and was significantly greater than that of normal subjects an average of 3 years after surgery.

Adult↗

PubMed2003

Low-grade fibrosarcoma of the proximal humerus.

We present the clinical, radiographical and pathological features of low-grade fibrosarcoma of the left proximal humerus in a 23-year-old man in whom it was necessary to distinguish the tumor from desmoplastic fibroma, malignant fibrous histiocytoma and intramedullary well-differentiated osteosarcoma. The patient presented with a 10-day history of pain in his left upper arm sustained when trying to break his fall with his left hand when slipping in the street. Plain radiography revealed an expanding multilobular osteolytic lesion from the proximal metaphysis to the diaphysis of his left humerus, accompanied by a pathological fracture at the distal portion of the lesion. Open biopsy of the lesion was performed twice; however, a conclusive diagnosis could not be obtained. The patient underwent wide excision and prosthetic replacement of the left proximal humerus. Histologically, the resected tumor was composed of both cellular areas and hypocellular areas. Cellular areas revealed a proliferation of bundles of uniform fibroblastic spindle-shaped cells with minimal cellular atypia, mixed with abundant intercellular collagenization. Mitotic figures were occasionally seen. Hypocellular areas showed myxoid features with loose bundles of collagen fibers. The patient demonstrates no evidence of disease 42 months after surgery. It is important to detect the scant atypical cells for the differential diagnosis of low-grade fibrosarcoma and desmoplastic fibroma of bone.

Adult↗

PubMed2003

Altered expression of cell cycle regulators in myxofibrosarcoma, with special emphasis on their prognostic implications.

Myxofibrosarcoma/myxoid malignant fibrous histiocytoma (MFH) has continued to be considered a distinct entity even after recently published reassessments of pleomorphic sarcomas and MFH. Several cell cycle-regulated proteins have already been screened by immunohistochemistry with the aim of finding the reliable prognostic indicator of soft tissue sarcomas; however, it is still unknown whether their altered expression affects patient survival in myxofibrosarcoma. In this study, we evaluated the expression of p53, MDM2, MIB-1 (Ki-67), p21, p27, p16, cyclin A, cyclin D1, and cyclin E by immunohistochemistry in 45 cases of myxofibrosarcoma. First, we searched for possible clinicopathologic prognostic factors in 61 cases of myxofibrosarcoma for which follow-up data were available. In univariate analysis, large tumor size (> or =5 cm), deeply situated tumor, and high histological grade (grade 2 or 3) significantly decreased survival (log-rank test, P <0.05). Among 43 cases of myxofibrosarcoma for which immunohistochemical findings were available, high MIB-1 labeling index (LI) (cutoffs of 10 and 22.5 on average), high cyclin A LI (cutoffs 10% and 13.8% on average), low p21 LI (cutoffs 10 and 20.7 on average), and reduced abnormal expression of p16 were adverse prognostic factors. In multivariate analysis (Cox proportional hazards model), high mitotic rate (>15/10 high-power fields), p53 immunoreactivity (cutoff 10%), high MIB-1 LI (>22.5), low p21 LI (<20.7), and low p27 LI (<47.8 on average) were independent poor prognostic factors. Our results suggest that reduced expression of p21 could be considered a new parameter to be evaluated, along with classical clinicopathologic prognostic factors, for identifying those at high risk for myxofibrosarcoma.

Adult↗

PubMed2003

Tibial shaft axis does not always serve as a correct coronal landmark in total knee arthroplasty for varus knees.

Predicted postoperative knee alignment was calculated when total knee arthroplasty was performed after 1 of 3 different methods of tibia preparation in 30 osteoarthritic knees with varus deformity. In Method 1, the tibia was cut perpendicular to the tibial shaft. In Method 2, the tibia was cut perpendicular to a line connecting the center of the tibial plateau and the center of the talar dome. In method 3, tibial resection was determined with an original template so that tibial resection would be perpendicular to a line connecting the center of the resected tibial plateau and the center of the talar dome. Methods 1 and 2 caused significantly more valgus alignment than Method 3 (P<.0001). The postoperative weight-bearing ratio was in Method 1, 57.7%, in Method 2, 53.6% and 50.0% in Method 3. These results suggest that cutting the tibia perpendicular to the tibial shaft can cause valgus alignment in total knee arthroplasty for varus knees.

Analysis of Variance↗

PubMed2003

Medial torsion of the tibia in Japanese patients with osteoarthritis of the knee.

To assess the reliability of the landmarks for the rotationally neutral alignment of the tibial component in total knee arthroplasty for Japanese patients, the rotational position of the medial (1/3) of the tibial tuberosity relative to the femoral epicondylar line (Angle TT) and that relative to the center of the ankle (Angle TT-AA) were measured in 24 knees with medial femorotibial osteoarthritis and in 28 normal knees by computed tomography. Angle TT-AA shows the degree of medial torsion of the tibia. The range of Angle TT and that of Angle TT-AA each was greater than 40 degrees. The position of the tibial tuberosity and degree of medial torsion of the tibia varied by individual. In patients with severe medial torsion, the internal rotation of the foot is extreme if the medial (1/3) of the tibial tuberosity is used for the rotationally neutral alignment of the partially constrained tibial component. In the treatment specifically of patients from East Asian countries, medial torsion of the tibia should be taken into account in total knee arthroplasty to ensure proper patellar tracking and proper rotation of the foot in knees with medial femorotibial osteoarthritis.

Adult↗

PubMed2003

A comparison of rotational landmarks in the distal femur and the tibial shaft.

The relationship among three anatomic landmarks and the mechanical axis of the tibia was evaluated using magnetic resonance imaging in 30 normal knees in 15 healthy volunteers. These three relationships are calculated for flexion and extension. The angles between the tibial mechanical axis and a line perpendicular to the surgical epicondylar axis, a line perpendicular to the clinical epicondylar axis, and the anteroposterior axis were 3.9 degrees varus, 0.6 degrees varus, and 0.2 degrees valgus, respectively. The mechanical axis of the femur was 3.0 degrees varus relative to the mechanical axis of the tibia. The results of the current study suggest that the surgical epicondylar axis rather than the clinical epicondylar axis or the anteroposterior axis can maintain a more predictable orientation with respect to the mechanical axis of the tibia when moving from flexion into extension.

Adult↗

PubMed2003

Comparison between the shape of resected femoral sections and femoral prostheses used in total knee arthroplasty in Japanese patients: simulation using three-dimensional computed tomography.

Simulation of the femoral cut for total knee arthroplasty was performed in 44 knees using three-dimensional computed tomography. The three-dimensional images were measured, and the shape of the femur was compared to the provided femoral prosthesis. The ratio between the medial-lateral and anteroposterior dimensions of the three-dimensional images did not always match the prosthesis. The widths of the medial condyles of the three-dimensional images tended to be larger than those of the prosthesis. The lengths of the lateral posterior condyles of the three-dimensional images tended to be shorter than those of the prosthesis. These results suggest that a new prosthesis should be designed to achieve a better anatomical fit.

Aged↗

PubMed2003

Alignment in total knee arthroplasty following failed high tibial osteotomy.

In total knee arthroplasty (TKA) following failed high tibial osteotomy, the mechanical axis does not intersect the center of the tibial component if the tibia has been resected perpendicular to the anatomical axis. Therefore, tibial resection referencing the predicted postoperative mechanical axis instead of the tibial shaft axis is advocated. To obtain the optimal tibial resection, characteristics of the tibial proximal deformity were measured radiographically and predicted postoperative lower limb alignment was calculated using full-length, weight-bearing, lower limb anteroposterior radiographs. Two finite element analysis models also were examined. The proximal tibia was resected perpendicular to the tibial shaft axis in model 1, and perpendicular to the predicted postoperative tibial mechanical axis in model 2. When the proximal tibia was resected perpendicular to the tibial shaft axis, the predicted lower limb mechanical axis was significantly shifted medially to the center of the tibial joint surface. The results of the finite element analysis reflected the medial shift of the lower limb mechanical axis in model 1, where stresses were increased in the medial tibial compartment. Tibial resection referencing the predicted postoperative tibial mechanical axis, instead of the tibial shaft axis, should be performed, especially in cases with a deformed tibia.

Aged↗

PubMed2002

Possible involvement of the vascular endothelial growth factor-Flt-1-focal adhesion kinase pathway in chemotaxis and the cell proliferation of osteoclast precursor cells in arthritic joints.

Vascular endothelial growth factor (VEGF) plays a crucial role in the pathogenesis of inflammatory joint disease, including angiogenesis and synovitis. Rheumatoid arthritis is a chronic inflammatory disease characterized by progressive synovitis and subsequent bone destruction mediated by osteoclasts (OCs). In this study, we investigate the effects of VEGF on OC precursor cells (pOCs) using Raw cells and adjuvant-induced arthritis in rats. OCs and pOCs in the arthritic joints express VEGF and VEGF receptor type I (Flt-1). Raw cells also express Flt-1, and VEGF treatment stimulated chemotaxis, cell proliferation, the association of Flt-1 with focal adhesion kinase (FAK), and the tyrosine phosphorylation of FAK in Raw cells. The tyrosine phosphorylation of FAK was also observed in pOCs in the arthritic joints of adjuvant-induced arthritis. Adenovirus-mediated expression of FAK-related nonkinase in Raw cells inhibited the effects of VEGF in a dominant negative manner. Furthermore, intra-articular injection of the FAK-related nonkinase virus suppressed the recruitment of pOCs and bone destruction. Our results suggest the possible involvement of the VEGF-Flt-1-FAK pathway in inflammatory disease-induced joint destruction.

Animals↗

PubMed2002

APC mutations in synovial sarcoma.

It has previously been demonstrated that accumulated beta-catenin serves as an oncoprotein in synovial sarcoma and results in a poor overall survival rate, but the frequency of beta-catenin mutation was quite low (8.2%). The present study, using essentially the same study group of cases, screened for genetic alterations in the mutation cluster region (MCR) of the APC gene in 49 cases of synovial sarcoma. SSCP analysis followed by DNA direct sequencing revealed five missense APC mutations in four cases of synovial sarcoma (8.2%). The mutational sites comprised one case each at codons 1299 (GCT to ACT, Ala to Thr), 1412 (GGA to AGA, Gly to Arg), and 1414 (GTA to ATA, Val to Ile), in addition to one case with double point mutations at codon 1398 (AGT to AAT, Ser to Asn) and at codon 1413 (ATG to ATA, Met to Ile), together with beta-catenin mutation at codon 32 (GAC to TAC, Asp to Tyr). All four cases with APC mutations were histologically of the monophasic fibrous type and showed beta-catenin accumulation. All three cases with APC mutations available for follow-up data were long survivors. This study provides the first evidence that APC mutations also occur in the field of sarcoma, especially in synovial sarcoma.

Adult↗

PubMed2002

Vascular compression caused by solitary osteochondroma: useful diagnostic methods of magnetic resonance angiography and Doppler ultrasonography.

Osteochondroma is a common benign bone tumor that sometimes causes vascular complications when the lesion is situated near the knee. Venous complications are seen less frequently. We report two cases of solitary osteochondroma that arose in the distal femur. The patients were an 11-year-old boy and a 16-year-old boy, both of whom were suffering from bone protuberance and lower leg swelling due to congestion. In both patients, magnetic resonance imaging (MRI) revealed dilated popliteal veins at a site distal from the tumors or superficial veins. MR angiography (MRA) showed compressed popliteal arteries, and Doppler ultrasonography revealed weaker blood flow in the dorsalis pedis arteries in the lower leg with the tumor than in the other lower leg. The former patient complained of pain due to swelling in the lower leg, and for this reason the patient underwent resection of the tumor. After resection, both the swelling and the pain were decreased, and Doppler ultrasonography also revealed normal blood flow in the artery. The latter patient had swelling, but no pain, in the lower leg, and accordingly this patient has been followed carefully without resection, since there is always the possibility of irreversible vascular damage caused by osteochondroma, such as arterial or venous occlusion. We present two patients with osteochondroma, both of whom suffered from swelling of the lower leg due to venous compression by the tumor. In both cases, MRI and MRA were useful to show the presence of vascular compression. Doppler ultrasonography could also reveal the blood flow disturbance objectively, even in current osteochondroma cases in which there were no arterial symptoms.

Adolescent↗

PubMed2002

High-dose chemotherapy and autologous peripheral blood stem-cell transfusion after conventional chemotherapy for patients with high-risk Ewing's tumors.

Although the overall results of treatment of Ewing's tumors have improved, patients with high-risk factors, including metastatic disease at diagnosis, bulky primary tumors, axial sites, and age >15 years, continue to have poor prognoses. The effects of high-dose chemotherapy and autologous peripheral blood stem-cell transplantation on high-risk Ewing's tumor patients have been reported. In most of these studies, conditioning and high-dose regimens varied among patients. Here we report the feasibility and effects of a high-dose chemotherapy regimen conducted in our institution. Seven patients with high-risk Ewing's tumors were treated by high-dose chemotherapy. The patients received four cycles of remission induction chemotherapy, and then peripheral blood stem cells were mobilized by high-dose etoposide and harvested. Myeloablative chemotherapy consisted of carboplatin, ifosfamide, and etoposide. The patients have 5-year overall and relapse-free survival probabilities of 0.86 and 0.81, respectively. The results were significantly better than those for patients treated with conventional chemotherapy alone. None of the patients had severe side effects. The high-dose regimen and transplantation were feasible and well tolerated. The poor prognoses of high-risk Ewing's tumor patients may be improved by high-dose chemotherapy with peripheral blood stem cell transplantation. However, the real impact of the therapy on the clinical outcome of patients with high-risk Ewing's tumors should be evaluated in a prospective, randomized study.

Adolescent↗