[Show abstract][Hide abstract] ABSTRACT: Multinucleated cells are frequently seen in association with a malignant neoplasm. Some of these multinucleated cells are considered to be neoplastic. The mechanism of neoplastic multinucleation remains unknown, but is considered to be induced by either cell-cell fusion or acytokinetic cell division. Myxofibrosarcoma consists of spindled and pleomorphic tumor cells and bizarre multinucleated giant cells. Some of these multinucleated cells are considered to be neoplastic.
We studied the mitotic activity of the multinucleated cells by Ki-67 immunohistochemistry, and the dynamics and differentiation by live-cell video microscopy in the two myxofibrosarcoma cell lines to determine whether the mechanism of multinucleation is cell-cell fusion or acytokinetic cell division
A Ki-67 immunohistochemical analysis revealed a high positive rate of multinucleated cells, as well as mononuclear cells, and mitotic ability was shown in the multinucleated cells. In live-cell video microscopy, most of the multinucleated cells were induced via the process of acytokinetic cell division.
The current study indicates that a vulnerability of the cytoskeleton components, such as the contractile ring, causes multinucleation to occur from the telophase to the cytokinesis of the cell cycle.
Journal of Experimental & Clinical Cancer Research 04/2009; 28(1):44. DOI:10.1186/1756-9966-28-44 · 4.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite accumulating knowledge of chimeric genes derived from fusion of the HMGA2 gene with multiple partners in lipomas, the different clinicopathological features of lipomas depending on different gene aberrations have not been well documented. The purpose of this study was to examine the clinical significance of the expression of fusion genes in lipomas.
The expressions of three previously reported gene fusion transcripts, including HMGA2/LPP, HMGA2/RDC1 and HMGA2/NFIB, were analyzed in 102 tumors from patients with lipomas.
There were 23 cases (22.5%) expressing HMGA2/LPP, 2 cases (1.9%) expressing HMGA2/RDC1 and no cases of HMGA2/NFIB expression (0%). There were no significant intergroup differences in age, gender, body mass index, tumor size or location. The magnetic resonance images and pathological features were also not different in regard to the status of fusion gene expression.
There were no significant differences of clinicopathological features in patients with lipoma with or without these fusion gene transcripts.
Anticancer research 01/2008; 28(1B):535-8. · 1.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report a case of cystic teratoma of the diaphragm that was considered to be a soft tissue lipoma by the preoperative examination. A magnetic resonance imaging revealed an 8 x 8 cm well-demarcated, homogeneous mass. On T1- and T2-weighted imaging, the mass was isointense to fat. On the fat-suppressed imaging, the signal from the mass was reduced to the same degree as subcutaneous fat. We performed marginal excision. The tumor contained a large number of hairs and oily liquid; and it was connected to the diaphragm.
[Show abstract][Hide abstract] ABSTRACT: Dedifferentiated chondrosarcoma is a rare, highly malignant variant of chondrosarcoma in which a high-grade sarcoma coexists with a low-grade chondroid tumor. We herein review a case of dedifferentiated chondrosarcoma with an osteosarcoma omit component that occurred in the distal femur of a 38-year-old man. We established the cell line (NDCS-1) from a pleural effusion of the metastatic lung tumor. The cell line was characterized by a the G-banded karyotype, polymerase chain reaction (PCR) single-strand conformation polymorphism analysis, spectral karyotyping, and reverse transcriptase PCR (RT-PCR). The tumor exhibited complex karyotypes and a high frequency of chromosomal amplication with p53 mutation. This tumor revealed an osteoblastic and chondroblastic character in vitro and in severe combined immunodeficiency mice. The expression and phosphorylation of platelet-derived growth factor receptor-beta, which seemed to play a major role in the malignant phenotype of chondrosarcoma, was confirmed by RT-PCR and Western blotting. To our knowledge, this is the first report of the establishment of a human dedifferentiated chondrosarcoma.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 10/2007; 451(3):691-9. DOI:10.1007/s00428-007-0426-3 · 2.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report on a case of a solitary fibrous tumor that developed in the thigh of an 82-year-old woman. The tumor was composed of areas of high-grade sarcoma and typical solitary fibrous tumor. Its karyotype was: 70,XXX,+X,+1,add(1)(p36),add(1),+2,-3,+6,add(6)(p11)x2,+7,+9,-11,-12,-13,add(13)(p11)x2,-14,+15,-16,-17,-19,+20,,+21,+22,+mar1x2[cp4].
Cancer Genetics and Cytogenetics 09/2007; 177(1):55-8. DOI:10.1016/j.cancergencyto.2007.04.016 · 1.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ossifying fibromyxoid tumor (OFMT) is a rare but morphologically distinctive soft-tissue tumor. The histologic origin of this tumor is not clearly known, but its various features suggest a schwannian, neuronal, or chondroid origin. We herein report a case of a typical OFMT that occurred in the shoulder of a 65-year-old man. The karyotype exhibited the following complex numeric and structural aberrations: 42 approximately 46,XY,-Y,add(1)(q42),add(6)(p21),t(10;18)(q26;q11),der(11)t(11;15)(q23;q15),add(12)(q13),ins(14;?)(q13;?),-15,+mar. Combined with several previously reported studies, these aberrations could not identify a common cytogenetic abnormality in OFMT.
Cancer genetics and cytogenetics 08/2007; 176(2):156-60. DOI:10.1016/j.cancergencyto.2007.04.009 · 1.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Malignant peripheral nerve sheath tumor (MPNST) is a relatively rare soft tissue tumor, and its clinical relevance of pathological grades remains obscure.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: Description of surgical technique and retrospective review of 13 cases.
To describe the surgical technique of margin-free spondylectomy and the outcome of 13 cases and to discuss the advantages and limitations of the procedure.
Recently, spondylectomy became a standard procedure by several pioneers. For extended malignant spine tumors involving pedicles or epidural space, however, performing an "en bloc" resection with a tumor-free margin remains a challenge.
Our procedure consists of a combined anterior and posterior procedure with one or two stages. In the anterior procedure, tumor vertebrae are covered by the pleura or psoas muscles as a barrier. The posterior procedure includes decompression through the intact posterior elements, coverage of the tumor with all possible soft tissue barriers, and en bloc extirpation by rotating the tumor vertebrae around the spinal cord. We performed this procedure in 13 cases: 3 chondrosarcoma, 3 giant cell tumor, 1 osteosarcoma, 1 chordoma, and 5 metastases.
Neurologic status and pain improved in all cases except asymptomatic cases. There was no local recurrence, except in 2 cases (chondrosarcoma with extirpation of 5 vertebrae, chordoma with multiple previous surgeries). Two cases of chondrosarcoma were disease-free 14 years and 13 years after surgery, respectively.
Although the best chance for a cure in extended malignant tumors of the spine is realized through wide resection, the procedure is not yet standardized. Margin-free spondylectomy is technically demanding, but the procedure can be used with a confidence as a more radical surgery for tumors extending to the epidural space and the unilateral pedicle. A key to success is the surgical technique, including a 360 degree dissection around the tumor vertebrae, instrumentation, and removal of the lesion with all possible soft tissues maintained intact to function as a barrier, like the dura mater.
[Show abstract][Hide abstract] ABSTRACT: Despite its benign nature, a ganglion can be problematic. We successfully treated a patient with large painful ganglion in his ankle by OK-432 (lyophilized incubation mixture of group A Streptococcus pyogenes of human origin) injection. OK-432 injection seems to be a safe, convenient, and effective alternative to surgical treatment for either symptomatic or recurrent ganglia.
Modern Rheumatology 02/2007; 17(4):341-3. DOI:10.1007/s10165-007-0597-4 · 2.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Prominent osteoconductive activity and the biodegradable nature of commercially available beta-tricalcium phosphate (beta-TCP, OSferion) have been documented in animal experiments. We analyzed four cases of involving grafted OSferion in human bone with respect to histological features by routine hematoxylin and eosin staining, silver impregnation, immunohistochemistry and in situ hybridization. OSferion affords early bioresorption by osteoclasts, vascular invasion of macropores and osteoblastic cell attachment on the surface on the ceramic surface 14 days after grafting. Prominent bone formation and direct bone connection between preexisting bone and OSferion were evident 28 days after grafting. Nearly the entire TCP surface was covered by lamellar bone; additionally, active osteoblastic lining and attachment of the osteoclast-like giant cells were not observed 72 weeks after grafting. Silver impregnation revealed the presence of collagen fibrils within probable micropores of OSferion.
[Show abstract][Hide abstract] ABSTRACT: Activating Gs a mutations have been identified in most instances of fibrous dysplasia (FD). This mutation leads to consistently elevated intracellular cyclic adenosine monophosphate (cAMP) levels, with various biological consequences. The development of secondary sarcoma in FD is a rare but well-established phenomenon. This finding raised the possibility that a common gene mutation exists in these tumors.
The expression of the Gs a mutation was examined in 16 cell lines and 173 musculoskeletal tumor tissues, including 13 cases of FD, via RT-PCR and sequence analysis.
No expression of a Gs a mutation was detected in any cell line or clinical tissue sample, excluding FD tissues. Direct sequence analysis demonstrated results identical to those of RT-PCR.
Activating Gs a mutation rarely occurs in musculoskeletal tumors other than FD. The occurrence of most sarcomas displays no correlation with Gs a mutations.
Anticancer research 03/2006; 26(2B):1611-4. · 1.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The present investigation examined the effect of bisphosphonates on six mesenchymal tumor cell lines and the mechanisms of inhibition of tumor cell proliferation. HT-1080, a fibrosarcoma cell line that exhibits increased Ras activity due to a mutation of the Ras gene, demonstrated significantly reduced tumor cell proliferation upon treatment with incadronate. The other cell lines, however, which lack mutation of the Ras gene, showed no influence upon treatment with incadronate. Autoradiography demonstrated no difference in the uptake of 3H-labelled incadronate between susceptible and unaffected cells. The anti-proliferation of HT-1080 was reversed by the addition of geranylgeranyl pyrophosphate. Etidronate exhibited no influence on all tested cell lines. On the basis of these data, we hypothesized that incadronate inhibits the mevalonate pathway and blocks oncogenic Ras signaling. In an effort to confirm this hypothesis, the influence of incadronate on an oncogenic Ras transfected BALB/3T3 cell line (Bhas 42) and a parental BALB/3T3 cell line were compared. The parental BALB/3T3 cells showed slight inhibition upon treatment with incadronate, however, the proliferation of Bhas 42 cells was significantly reduced. These results suggest that incadronate suppresses oncogenic Ras-activated mesenchymal tumors through the inhibition of Ras signaling pathways.
Journal of experimental & clinical cancer research: CR 12/2005; 24(4):617-24. · 4.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report a case of successful control of the infection of megaprosthesis in the distal femur. Deep infection occurred 5 years after the resection of the osteosarcoma and reconstruction with cementless megaprosthesis. Multiple debridement and intravenous administration of antibiotics did not eradicate the infection. He developed aortitis syndrome (Takayasu's arteritis) and needed to undergo steroid therapy. Total removal of the prosthesis achieved good control of the infection, and the patient had started prednisolone therapy. The patient can walk alone with an ischial weight-bearing brace. Removal of the endoprosthesis and application of ischial weight-bearing brace may be a possible option for the treatment of infected megaprosthesis.
The Journal of Arthroplasty 11/2005; 20(7):954-6. DOI:10.1016/j.arth.2005.07.004 · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This report describes a case of congenital dermatofibrosarcoma protuberans (DFSP) with fibrosarcomatous (FS) and myxoid areas. Immunohistochemical results showed that tumour cells in ordinary DFSP areas were diffusely positive for CD34, whereas in the FS and myxoid areas, few tumour cells were positive for this antigen. Ki-67 positive tumour cell numbers were greater in the FS (11.8%) and myxoid areas (19.8%) relative to ordinary DFSP areas (2.2%). Reverse transcription polymerase chain reaction and sequence analysis showed the presence of an identical COL1A1-PDGFB fusion transcript in ordinary DFSP (plaque-like area), FS, and myxoid areas of DFSP. These results indicate that the three components of DFSP have a common histogenesis. This study documents the first application of gene analysis involving the myxoid area of DFSP.
[Show abstract][Hide abstract] ABSTRACT: We established a novel human myxofibrosarcoma cell line NMFH-1 and analyzed it with spectral karyotyping and comparative genomic hybridization (CGH). NMFH-1 cells are composed of two different types of cells, small, spindle-shaped mononuclear cells and bizarre multinucleated giant cells, which were maintained in vitro over 200 passages. Xenografted tumor showed typical features of myxofibrosarcoma, which included bizarre multinucleated giant cells. Cytogenetic analyses revealed complex abnormalities, including a t(17;22)(q2?2;q13), which has been found in dermatofibrosarcoma protuberans. Subsequent reverse-transcription polymerase chain reaction revealed that the cell line did not have the COL1A1-PDGFB gene fusion. Significant gains of the 1q12 approximately q23 and 8q13 approximately qter regions and loss of the 9p21 approximately pter and 13q12 regions often found in MFH were observed by CGH analysis. We investigated the origin of multinucleated giant cells in xenografted tumor through DNA in situ hybridization. In this system, the human-specific Alu sequence and the mouse L1 sequence were used as specific cell markers of identity. In situ hybridization revealed neoplastic proliferation of the multinucleated giant cells of human origin.
Cancer Genetics and Cytogenetics 09/2005; 161(1):28-35. DOI:10.1016/j.cancergencyto.2005.02.003 · 1.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We examined osteochondral autografts, obtained at a mean of 19.5 months (3 to 48) following extracorporeal irradiation and re-implantation to replace bone defects after removal of tumours. The specimens were obtained from six patients (mean age 13.3 years (10 to 18)) and consisted of articular cartilage (five), subchondral bone (five), external callus (one) and tendon (one). The tumour cells in the grafts were eradicated by a single radiation dose of 60 Gy. In three cartilage specimens, viable chondrocytes were detected. The survival of chondrocytes was confirmed with S-100 protein staining. Three specimens from the subchondral region and a tendon displayed features of regeneration. Callus was seen at the junction between host and irradiated bone.
The Bone & Joint Journal 08/2005; 87(7):1006-11. DOI:10.1302/0301-620X.87B7.14822 · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Germline mutation and functional loss of EXT1 or EXT2 are commonly found in multiple osteochondromas and predispose to the development of chondrosarcoma. Mutations of EXT1 and EXT2 have rarely been detected in sporadic secondary chondrosarcomas from osteochondroma; these frequently display loss of heterozygosity at the EXT1 and EXT2 loci, but primary chondrosarcomas typically do not. To evaluate promoter methylation (which is an epigenetic gene silencing mechanism) of EXT1 and EXT2, we performed methylation-specific polymerase chain reaction (PCR) for 20 chondrosarcoma cases (12 primary, 3 secondary to osteochondroma, 2 secondary to enchondromatosis, 2 extraskeletal ordinary, and 1 clear cell) and in five cell lines. In addition, mutation analysis of the EXT1 and EXT2 coding regions was performed using PCR-single-strand conformation polymorphism and sequencing analysis for 12 of the 20 chondrosarcoma cases (8 primary, 1 secondary to enchondromatosis, 1 secondary to osteochondroma, and 2 extraskeletal ordinary) and five cell lines. Promoter methylation of EXT1 and EXT2 was not detected in any of the cases, and both EXT1 and EXT2 were expressed in all cell lines. Two missense mutations in EXT2 (D227E and R299H) were detected among the chondrosarcoma cases. When considering tumor development in primary chondrosarcoma, we should include mutations in EXT2, along with the status of other members of the EXT gene family.
Cancer Genetics and Cytogenetics 05/2005; 158(2):148-55. DOI:10.1016/j.cancergencyto.2004.08.031 · 1.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We describe two patients with a diffuse haemangioma of the lower limb complicated by pathological fracture of the femoral shaft, one of whom was treated by a bone graft and immobilisation in a cast, and the other by external fixation and injection of bone marrow. A review of the literature identified difficulty in control of bleeding and obtaining bony union.
The Bone & Joint Journal 04/2005; 87(3):412-4. · 2.80 Impact Factor