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Biomedical subjects

Katsuyuki Kusuzaki

Publications and source records attributed to Katsuyuki Kusuzaki.

At least 19 recordsLinked to original sources
PubMed2006

Expression of hypoxia-inducible factor (HIF)-1alpha as a biomarker of outcome in soft-tissue sarcomas.

Hypoxia-inducible factor (HIF)-1alpha is a transcription factor that supports the adaptation of human cancer cells to hypoxia and tumor growth and progression. The overexpression of HIF-1alpha protein has been reported to be associated with a worse prognosis in various cancers. However, the expression of HIF-1alpha in soft-tissue sarcomas has not yet been characterized. The expression of HIF-1alpha protein was immunohistochemically determined in 49 specimens of soft-tissue sarcomas including malignant fibrous histiocytoma (29 patients), synovial sarcoma (12 patients), leiomyosarcoma (four patients), and malignant peripheral nerve sheath tumors (four patients). The 49 samples consisted of 40 primary lesions and nine local recurrences. An immunohistochemical analysis showed the nuclear accumulation of HIF-1alpha protein in 35 (71.4%) samples. The expression of HIF-1alpha was negative in 14 (28.6%) cases, weak in nine (18.4%), moderate in 17 (35.4%), and strong in nine (18.4%). The patients with a strong or moderate expression of HIF-1alpha had a significantly shorter overall survival rate in comparison with those with a weak or negative expression in a univariate analysis (P = 0.029; log-rank test) and multivariate analysis (P = 0.018). This is the first report that demonstrated an overexpression of HIF-1alpha protein to be an independent prognostic factor for soft-tissue sarcomas.

Adult↗
PubMed2006

Calcium phosphate cement in musculoskeletal tumor surgery.

BACKGROUND AND OBJECTIVES: Calcium phosphate cement (CPC) is an injectable biocompatible bone substitute that has been used for various applications in orthopedic surgery. However, no extensive clinical studies of the use of CPC to fill bone cavities after curettage of musculoskeletal tumors have been reported. The present study reviewed the results for 56 musculoskeletal tumors treated by curettage and CPC implantation. METHODS: Assessment was based on clinical examination and radiographic findings. Variables for clinical assessment included pain, limb function, and complications. Median follow-up was 18.5 months (range 6-47 months). RESULTS: One patient experienced post-operative fractures. Three patients displayed local recurrence. One patient developed post-operative superficial wound infection, and two patients with large bony defect exhibited non-infectious serous discharge. No serious adverse effects such as deep venous thrombosis, pulmonary embolism were encountered. In all cases, CPC was radiographically well adapted to the surrounding host bone as of final follow-up. CONCLUSIONS: CPC appears to offer a useful bone substitute for the treatment of musculoskeletal tumors. As the follow-up period for this study was short, further long-term follow-up studies are needed.

Adolescent↗
PubMed2006

Low-dose methotrexate inhibits lung metastasis and lengthens survival in rat osteosarcoma.

Lung metastasis is the most crucial event affecting the treatment of osteosarcoma and is dependent on tumor angiogenesis. To improve the prognosis for patients with osteosarcoma, prevention of lung metastasis is essential. Low-dose methotrexate is a useful drug for treating a variety of diseases. Low-dose methotrexate reportedly plays a role in antiangiogenesis for the synovial blood vessels in rheumatoid arthritis. However, whether low-dose methotrexate is correlated with tumor angiogenesis and metastasis is unclear. We investigated the inhibitory effect of methotrexate on lung metastasis in a rat osteosarcoma cell line with high metastatic potential, S-SLM. Two weeks after inoculation of S-SLM cells into male Fischer 344 rats, low-dose methotrexate (1.2 mg/kg once or twice a week) or saline was intraperitonealy injected for 4 weeks and the antimetastatic effect was evaluated. Low-dose methotrexate significantly reduced the number of lung metastatic nodules and the wet weight of the lungs. Immunohistochemical staining showed a decrease in microvessel density in the metastatic nodules. We also evaluated the effect of methotrexate on the proliferation of endothelial cells and S-SLM osteosarcoma cells in vitro. Methotrexate significantly inhibited the proliferation of endothelial cells at a lower concentration than that of S-SLM osteosarcoma cells. These data suggest that low-dose methotrexate inhibited lung metastasis of osteosarcoma through its antiangiogenic activity. Our results indicate that low-dose methotrexate is a promising drug for tumor dormancy therapy in patients with osteosarcoma and lung metastasis.

Animals↗
PubMed2006

Extraskeletal myxoid chondrosarcoma arising from the clavicle.

This report presents an extremely rare case of extraskeletal myxoid chondrosarcoma (EMC) arising from the clavicular periosteum. To the best of our knowledge, this may be the first detailed report of its clinicopathological findings. The patient was a 48-year-old man. Plain radiography and CT did not demonstrate any osteolytic lesion or periosteal reaction in the right clavicle. However, MRI showed an isosignal-intensity mass on T1-weighted images and a homogeneous high signal intensity lesion on T2-weighted images. The histological findings of the widely resected tumor were consistent with the diagnosis of extraskeletal myxoid chondrosarcoma. Preoperative diagnosis of extraskeletal myxoid chondrosarcoma at an unusual location, as in this case, is difficult not only with imaging examinations alone, but sometimes even after histological examination of biopsy specimens.

Bone Neoplasms↗
PubMed2005

Periosteal Ewing's sarcoma treated by photodynamic therapy with acridine orange.

We recently encountered a very rare case of periosteal Ewing's sarcoma (PES), which was treated by surgery followed by photodynamic therapy using acridine orange with radiodynamic therapy. No more than 15 cases of PES have been reported previously in literature. In our case, MRI revealed the tumor to be localized on the cortical surface of the proximal humerus. Histopathological examination of biopsy specimens revealed a small round cell sarcoma suggestive of Ewing's sarcoma or PNET, and immunohistochemistry showed positive staining for MIC2. Although fusion genes EWS-FLI1 and EWS-ERG were undetectable, PES was still considered to be the most likely diagnosis. Therefore, we administered preoperative chemotherapy, as a result of which the tumor shrank to 48% of its original volume. With a view to preserve excellent shoulder and upper limb function, we attempted intralesional tumor resection supported by photodynamic therapy using acridine orange with radiodynamic therapy. After surgery followed by postoperative chemotherapy, the patient has, until the time of writing, had no local tumor recurrence and no evidence of metastatic disease, and can move his shoulder fully and throw a ball well. Since it has been reported that PES has a better prognosis and responsiveness to chemotherapy than intramedullary Ewing's sarcoma, we believe that such reduction surgery with photodynamic therapy might be the strategy of choice to obtain satisfactory limb function in cases of PES.

Acridine Orange↗
PubMed2005

Metastasis of malignant peripheral nerve sheath tumor to free vascularized myocutaneous flap.

The vascularized free myocutaneous flap graft, a recent advance in microsurgery, is a very useful reconstruction technique for covering massive soft tissue defects or muscular dysfunction caused by wide resection for malignant soft tissue tumors. We have used this technique to treat many patients after resection for malignant soft tissue tumors. Recently we encountered a case in which a malignant peripheral nerve sheath tumor (MPNST) metastasized to a vascularized free myocutaneous flap used for limb reconstruction surgery after wide resection of a primary lesion. To our knowledge, there have been no previous reports of metastasis of a malignant soft tissue tumor (or any other cancer) to a grafted cutaneous or myocutaneous flap.

Aged↗
PubMed2004

Metastatic bone disease: pathogenesis and new strategies for treatment.

Bone is the third leading site of metastatic disease, after the lung and liver. Pain, pathological fractures, neurological deficits, and forced immobilization significantly decrease the quality of life of patients with bone metastasis. The development of metastasis, from the migration of malignant cells from the primary tumor to their proliferation at a distant site, involves a series of sequential steps: angiogenesis, matrix degradation, cell motility, cell attachment, and cellular proliferation. A better understanding of the pathogenesis of metastasis may be expected to lead to the development of new treatment modalities for bone metastasis. Currently, antiangiogenic agents, matrix metalloproteinase (MMP) inhibitors, and hyperthermia are some of the newer therapeutic modalities that seem to hold promise for the treatment of metastatic bone disease.

Angiogenesis Inhibitors↗
PubMed2004

Thrombin inhibitor, argatroban, prevents tumor cell migration and bone metastasis.

It is well known that malignant cells show procoagulant activity, which is associated with their metastatic potential. Thrombin, the key enzyme of the blood coagulation system, is generated around tumor cells, promoting the migration and metastasis of tumor cells. In this study, we evaluated the effect of argatroban, a specific thrombin inhibitor, on the migration and metastasis of B16BL6 melanoma cells. In vitro argatroban dose-dependently inhibited cell migration, the maximum inhibition being observed in the presence of 10 microM argatroban (p < 0.0001). In order to investigate the antimetastatic effect of the thrombin inhibitor, we used an animal model that we have reported previously. C57BL6 mice which had received a bone (femur or tibia) transplanted into the dorsal subcutis were injected with B16 melanoma cells into the left heart ventricle. Intraperitoneal injection of argatroban (9 mg/kg/day for 4 weeks) significantly reduced the number of limbs with metastatic lesions as compared to a placebo (p < 0.05). These results suggest that argatroban was associated with reduced melanoma metastases by inhibiting cell migration. Our results showed that argatroban is effective for treatment of bone metastasis.

Animals↗
PubMed2004

Surrounding muscle edema detected by MRI is valuable for diagnosis of intramuscular myxoma.

We recently experienced 4 cases of intramuscular myxoma and analyzed MRI findings, comparing them with histological ones. Results showed that all tumors were depicted with a homogeneous low signal intensity on T1-weighted images and a markedly high signal intensity on T2-weighted images, findings which are similar to those of cystic lesions like intramuscular ganglions. However, tumors were diffusely and finely enhanced on T1-weighted images with intravenous gadolinium administration. Three cases showed the characteristic fat rim and fat cap. A diffuse edematous lesion demonstrating intermediate signal intensity on T1-weighted images and high signal intensity on T2-weighted images was also found in the adjacent muscle surrounding the tumor in 3 of 4 cases. In this lesion, tumor invasion, diffuse and severe muscle degeneration, blood and lymphatic congestion with exudates, and reactive adipose tissue formation were observed. The present results suggested that for the clinical diagnosis of intramuscular myxoma with MRI examination, the combination of three MRI signs such as homogeneous low signal intensity on T1-weighted mages, markedly high signal intensity on T2-weighted images, and an enhancement effect with contrast medium are important, but the fat rim or fat cap, and the surrounding muscle edema as detected by MRI are also characteristic and allow for a more firm diagnosis. We presume that the diffuse and severe muscle fiber degeneration induced by tumors may cause such specific surrounding muscle edema.

Aged↗
PubMed2003

Successful treatment with Erwinia L-asparaginase for recurrent natural killer/T cell lymphoma.

We describe a patient with natural killer (NK)/T cell lymphoma who relapsed after autologous peripheral blood stem cell transplantation (auto-PBSCT) and was successfully treated with Escherichia coli (E. coli) and Erwinia L-asparaginase. A 38-year-old male patient with ulcerated tumor at the left thigh was diagnosed as having nasal type NK/T cell lymphoma on the basis of histopathological and flowcytometric findings of tumor, revealing diffuse infiltration of atypical lymphoid cells into blood vessels and expression of CD7 and CD56 antigens, but not CD3. He had tumor infiltration in the bone marrow and at the right lower lung field. After five cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) therapy, the patient achieved complete remission and received high-dose chemotherapy with auto-PBSCT, although the tumor recurred in the right leg 10 months later. Despite salvage chemotherapy, followed by local irradiation and surgical amputation, a tumor recurred at the left upper gingiva 10 days after. Using E. coli L-asparaginase (6000 U/m2/day), the tumor regressed, fever was alleviated and the serum lactate dehydrogenase decreased to normal range after several days. The asparagine synthetase expression in tumor cells was immunohistochemically negative on paraffin-embedded tissues. Because of the anaphylactoid reaction developing after E. coli L-asparaginase, alternative Erwinia L-asparaginase (6000 U/m2/day) was administered, resulting in regression of tumor and fever lysis. L-asparaginase is a promising agent for the treatment of NK/T cell lymphoma.

Adult↗
PubMed2002

Genome-wide analysis of gene expression in synovial sarcomas using a cDNA microarray.

Among a histologically heterogeneous group of soft tissue sarcomas, synovial sarcoma (SS) is regarded as a "miscellaneous" entity of uncertain origin. Although recent molecular analysis has disclosed involvement of a specific chromosomal translocation in the pathogenesis of SS, its genetic features remain largely unclear. In the work reported here we examined genome-wide gene expression profiles of 13 SS cases and 34 other spindle-cell sarcoma cases by cDNA microarray consisting of 23,040 genes. A hierarchical clustering analysis grouped SS and malignant peripheral nerve sheath tumor into the same category, and these two types of tumor shared expression patterns of numerous genes relating to neural differentiation. Several genes were up-regulated in almost all SS cases, and the presumed functions of known genes among them were related to migration or differentiation of neural crest cells, suggesting the possibility of neuroectodermal origin of SS. Moreover, we identified a set of genes that divided SS cases into two putative subclasses, a feature that may shed light on novel biological aspects of SS in addition to those having to do with epithelial differentiation. These data have provided clues for understanding the origin and tumorigenesis of SS.

Cluster Analysis↗
PubMed2002

The characterization of the human Siah-1 promoter(1).

Siah-1, the human homologue of Drosophila seven in absentia, is related to apoptosis and tumor suppression. Although it was reported that the expression of Siah-1 is induced by p53 and p21/WAF1, little is known about the transcriptional regulation of the Siah-1 gene. To investigate the transcriptional regulation, we isolated and sequenced the genomic fragment of the Siah-1 promoter region. The Siah-1 promoter has no typical TATA box or CCAAT box. Transient transfection assays using reporter plasmids in which the promoter region of the Siah-1 gene was deleted or mutated showed that one Sp1 site was responsible for the basal promoter activity. In Northern blotting analysis, the expression of the Siah-1 gene was upregulated by p53, but activation of the reporter plasmid by the p53 co-transfection assay was not shown, suggesting that a p53 responsive element does not exist in the promoter region we examined in this study but might be present in another region.

5' Flanking Region↗
PubMed2002

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

Fusion genes consisting of TLS/FUS and CHOP or EWS and CHOP are characteristic markers for myxoid/round cell liposarcomas (MLS/RCLS). Several different structures of the fusion genes were reported in the case of the TLS/FUS-CHOP form, whereas only one type of structure has so far been found for the EWS-CHOP form, which consisted of exons 1 to 7 of the EWS and exons 2 to 4 of the CHOP gene. Here we describe a novel type of EWS-CHOP fusion gene in two cases of MLS/RCLS, which were found in a consecutive analysis of 21 cases. This fusion gene consisted of exons 1 to 10 of the EWS and exons 2 to 4 of the CHOP gene. The two cases with this fusion gene shared several clinical features, such as a large tumor mass, rapid and invasive growth, and local recurrence within 12 months after surgical resection. Histopathological findings also showed common features characterized by the diffuse proliferation of small spindle cells with a primitive mesenchymal appearance. The association of these clinical and histopathological features suggests a distinct biological property for this rare type of fusion product.

Adolescent↗
PubMed2002

Acridine orange excited by low-dose radiation has a strong cytocidal effect on mouse osteosarcoma.

The study was conducted to clarify the cytocidal effect of combination therapy consisting of administration of acridine orange (AO), which is a photosensitizer, and radiation therapy using in vitro and in vivo mouse osteosarcoma models. The results revealed that AO combined with low-dose X-ray irradiation of about 1-5 Gy had a strong cytocidal effect on the cultured mouse osteosarcoma cells regardless of their chemosensitivity, and that this combination therapy inhibited growth of the in vivo mouse osteosarcoma by induction of tumor necrosis. This effect was inhibited by L-histidine, but not by mannitol. These findings suggested that AO might be excited by X-rays and kill osteosarcoma cells through the release of singlet oxygen, which is toxic to living cells. This mechanism is similar to that of photodynamic therapy with AO.

Acridine Orange↗
PubMedDate not supplied

Clinical outcome of a novel photodynamic therapy technique using acridine orange for synovial sarcomas.

Synovial sarcoma (SS) is one of common malignant soft-tissue tumors and is encountered most commonly in children and young adults. It frequently involves or invades major neurovascular structures and bones, and its local recurrence rate after simple resection has been reported to be as high as up to 80%. Because major nerves and vessels, as well as an adequate amount of bone, must be preserved to restore excellent limb function in cases of SS, a surgical technique entailing a low risk of local recurrence is needed. Based on the findings of recent experimental studies conducted by us using a mouse osteosarcoma model, we developed a novel therapeutic technique for SS, consisting of reduction surgery followed by photodynamic therapy using acridine orange (AO-PDT), with or without X-ray irradiation at 5 Gy. A preliminary study revealed that low-dose X-rays also excite AO like photons. After an initial study on cell cultures, this novel technique was applied to six cases of SS. A follow-up of the subjects to determine the clinical outcome revealed that none of the cases treated by AO-PDT, including the four cases treated by additional 5 Gy irradiation and the two cases not receiving any radiation, showed any evidence of recurrence or local/systemic complications during the follow-up period of 19-51 months after the surgery. Therefore, we believe that AO-PDT with 5 Gy irradiation may be an excellent novel therapeutic modality with reduction surgery to salvage excellent limb function in SS involving major nerves and vessels or bones.

Acridine Orange↗
PubMedDate not supplied

Case report: recurrence of soft tissue MFH in bone due to minute intravenous tumor emboli detected by MRI.

We recently encountered a case with local recurrence of malignant fibrous histiocytoma (MFH) in the bone after wide resection, caused by minute intravenous tumor emboli which were retrospectively detected in MR imaging. The patient was a 69-year-old woman who initially noticed a mass in her left thigh. The tumor was diagnosed to be MFH, therefore a wide resection was performed; although the tumor was closely attached to the periosteum, it was not difficult to dissect the tumor subperiosteally from the cortex of the femur. The patient received postoperative brachytherapy, but no chemotherapy. Two years later, the tumor recurred with bony destruction of the femur. We reviewed the pre-operative films obtained by various imaging modalities, as well as the histology of the primary tumor, and found minute intravenous tumor emboli in the MR imaging obtained before surgery. Tumor emboli were also observed histologically in the small vessels of the surgically resected tumor. Such intravenous tumor emboli have recently been implicated in the development of regional bone metastasis near the site of the primary lesion in cases of malignant soft tissue tumors. Therefore, we concluded that the tumor recurrence in our case was caused by small tumor emboli invading the perforating veins of the femur. It is therefore emphasized that MR images should be carefully reviewed for the presence of such intravenous tumor emboli before surgery in cases of high-grade malignant sarcomas. As at the time of writing, our patient remains alive and disease-free, with no evidence of any local recurrence or distant metastasis after wide tumor resection for the recurrent tumor.

Aged↗
PubMedDate not supplied

Rapid recurrence of calcifying fibrous pseudotumor (a case report).

Calcifying fibrous pseudotumor is a benign tumor-like lesion characterized by the presence of a whorl bundle of collagen fiber with deposit calcification and infiltration of inflammatory cells. This lesion is reportedly rare and involves subcutaneous or deep soft tissue in the extremities, trunk, neck and so on. This tumor has low recurrence even if only simple excision or enucleation is performed. We report a case of calcifying fibrous pseudotumor arising in the nuchal lesion of an 8-year-old boy who had a local recurrence 18 months after a simple excision had been performed. The patient had no evidence of recurrence or metastasis 10 months after the second operation.

Calcinosis↗