Biomedical subjects

Satoshi Nagayama

Publications and source records attributed to Satoshi Nagayama.

At least 19 recordsLinked to original sources

PubMed2006

Expression of claudin7 is tightly associated with epithelial structures in synovial sarcomas and regulated by an Ets family transcription factor, ELF3.

Synovial sarcoma, a soft tissue sarcoma that develops in adults, is pathologically subclassified into monophasic spindle synovial sarcoma and biphasic synovial sarcoma with epithelial components. The molecular mechanism building the epithelial components in biphasic synovial sarcoma is totally unknown. Here we investigated claudins, critical molecules in the tight junction, in biphasic synovial sarcoma. Expression profiles of 21 claudins in 17 synovial sarcoma tumor samples, including 9 biphasic tumors, identified claudin4, claudin7, and claudin10 as biphasic tumor-related claudins, and immunohistochemical analyses demonstrated the localization of these claudins in the epithelial component in biphasic tumors, with claudin7 the most closely associated with the epithelial component. The mRNA expression and protein localization of claudin7 coincided with those of the ELF3, an epithelia-specific member of the Ets family of transcription factors. Luciferase reporter assays demonstrated that the presence of the Ets-binding site at -150 in the promoter region of the claudin7 gene was critical for the transcriptional activity, and gel shift and chromatin immunoprecipitation assays confirmed the binding of ELF3 to the Ets site at -150. Inhibition of ELF3 expression by small interfering RNA simultaneously down-regulated the mRNA expression of the claudin7 gene, and the introduction of ELF3 expression in claudin7-negative cell lines induced mRNA expression of the claudin7 gene. Therefore, the induction of claudin7 expression by ELF3 appears critical to the formation of the epithelial structures in biphasic synovial sarcoma.

Base Sequence↗

PubMed2006

Retrospective analysis of 45 consecutive patients with advanced gastric cancer treated with neoadjuvant chemotherapy using an S-1/CDDP combination.

BACKGROUND: Standard treatment for highly advanced gastric cancer (AGC) has not been established yet. Neoadjuvant chemotherapy (NAC) represents a promising approach, which may improve the prognosis of AGC. In this study, we analyzed the feasibility and efficacy of NAC with S-1 (TS-1)/cisplatin CDDP in order to design appropriate clinical trials for AGC. METHODS: Results for a series of 45 consecutive patients with AGC treated with S-1/CDDP induction chemotherapy since January 2002 were analyzed retrospectively. RESULTS: The primary tumor was resected in 36 of the 45 patients (resectability, 80.0%). Progression of the disease during chemotherapy was observed in 1 patient only (2.2%). No treatment-related deaths occurred, and serious adverse effects (grade 3-4) were noted in only 2.2% of the patients. The overall median survival time was 1.82 years. Especially noteworthy is that, in patients with highly advanced disease (pretreatment [c]-stage IV; n = 27), resectability was 66.7% and curative (R0) resection was possible in 10 patients. The median survival times for c-stage IV patients who had total, curative, and noncurative resections were 20.8, 22.3 and 12.6 months, respectively. R0 resection was possible for all c-stage III patients (n = 17), with a 2-year overall survival of 90.9%. The downstaging rate was 55.6% (20/36), resulting in a significantly improved prognosis for the downstaged patients (P = 0.012). CONCLUSION: Induction chemotherapy using S-1/CDDP for AGC appears to be a safe and promising treatment. We have therefore started two independent multiinstitutional clinical trials to evaluate the efficacy of this treatment.

Aged↗

PubMed2005

Increased intratumor Valpha24-positive natural killer T cells: a prognostic factor for primary colorectal carcinomas.

PURPOSE: Human invariant natural killer T (NKT) cells are novel, distinct lymphocyte populations with a restricted T-cell receptor repertoire (Valpha24-Vbeta11). They play a pivotal role in immunoregulation and in antitumor activities. This study focused on Valpha24+ NKT cells in colorectal carcinomas and their clinicopathologic significance. EXPERIMENTAL DESIGN: Valpha24+ NKT-cell infiltration immunohistochemistry was studied in a total of 103 colorectal carcinoma cases. The degree of NKT-cell infiltration in tumors was evaluated as low (<7 NKT cells/5 HPF) or high (> or =7 NKT cells/5 HPF). The correlation between the degree of infiltrated Valpha24+ NKT cells and clinicopathologic variables was studied statistically. RESULTS: A small number of Valpha24+ NKT cells were found in the normal colorectal mucosa (2.6 +/- 3.7 cells/5 HPF); however, their number increased remarkably in colorectal carcinomas (15.2 +/- 16.3 cells/5 HPF; P = 0.0003) and a majority showed phenotype of activation. Higher NKT-cell infiltration was more frequent in women than in men (P = 0.034) and correlated with fewer lymph node metastases (P = 0.042). Patients with high NKT-cell infiltration showed higher overall (P = 0.018) as well as disease-free (P = 0.0006) survival rates. Intratumor NKT-cell infiltration was an independent prognostic factor for the overall (P = 0.033) and disease-free (P = 0.0064) survival rates. CONCLUSIONS: Increased infiltration of Valpha24+ NKT cells was observed in colorectal carcinomas. Higher Valpha24+ NKT-cell infiltration in colorectal carcinomas was an independent prognostic factor for favorable prognosis.

Aged↗

PubMed2005

Therapeutic potential of antibodies against FZD 10, a cell-surface protein, for synovial sarcomas.

Genome-wide expression profiling revealed overexpression of the gene encoding frizzled homologue 10 (FZD 10), a cell-surface receptor for molecules in the Wnt pathway, as a potential contributor to synovial sarcomas (SS). Northern blotting and immunohistochemical staining confirmed that expression levels of FZD 10 were very high in nearly all SS tumors and cell lines examined but absent in most normal organs or in some cancers arising in other tissues. Treatment of human SS cells with small-interfering RNA (siRNA) to FZD 10 decreased the amount of its product and suppressed growth of SS cells. Moreover, a polyclonal antibody specifically recognizing the extracellular domain (ECD) of FZD 10 was markedly effective in mediating ADCC against FZD 10-overexpressing synovial sarcoma cells in vitro. Injection of the antibody into SS xenografts in nude mice attenuated tumor growth, and TUNEL assays revealed clusters of apoptotic cells in antibody-treated xenografts. Taken together, these findings suggest that a humanized antibody against FZD 10 might be a promising treatment for patients with tumors that overexpress FZD 10; minimal or no adverse reactions would be expected because FZD 10 protein is not abundant in vital organs.

Amino Acid Sequence↗

PubMed2005

Fas/CD95 signaling rather than angiogenesis or proliferative activity is a useful prognostic factor in patients with resected liver metastases from colorectal cancer.

BACKGROUND: The selection of resective therapy for colorectal hepatic metastases remains controversial. The aim of this study is to investigate the prognostic factors for patients with resected liver metastases from colorectal cancer by analyzing not only clinicopathological factors but also recent immunohistological markers. METHODS: Eighty-five patients underwent hepatic resection for metastatic colorectal cancer over the past 20 years. Fas/CD95 expression, microvessel density, and proliferating cell nuclear antigen (PCNA) proliferative activity were assessed with immunohistochemical methods in addition to the clinicopathological factors. Survival analysis was performed using the Kaplan-Meier method and Cox proportional hazards model, both univariately and multivariately. RESULTS: Univariate and multivariate analyses revealed that the number of metastases, Fas/CD95 expression, and postoperative carcinoembryonic antigen doubling time (CEADT) were significant prognostic indicators, whereas the mode of hepatic resection, chemotherapy, and other clinicopathological factors had no influence on survival. Fas/CD95 index correlated with postoperative CEADT (p=0.039), number of metastases (p=0.018), and survival (p=0.023). CONCLUSIONS: Our study confirmed the number of metastases and CEADT as prominent prognostic factors after hepatic resection for metastatic colorectal cancer. These two factors reflect the degree of Fas/CD95 signaling rather than angiogenesis or cancer growth rate.

Adult↗

PubMed2005

Disruption of fibroblast growth factor signal pathway inhibits the growth of synovial sarcomas: potential application of signal inhibitors to molecular target therapy.

PURPOSE: Synovial sarcoma is a soft tissue sarcoma, the growth regulatory mechanisms of which are unknown. We investigated the involvement of fibroblast growth factor (FGF) signals in synovial sarcoma and evaluated the therapeutic effect of inhibiting the FGF signal. EXPERIMENTAL DESIGN: The expression of 22 FGF and 4 FGF receptor (FGFR) genes in 18 primary tumors and five cell lines of synovial sarcoma were analyzed by reverse transcription-PCR. Effects of recombinant FGF2, FGF8, and FGF18 for the activation of mitogen-activated protein kinase (MAPK) and the growth of synovial sarcoma cell lines were analyzed. Growth inhibitory effects of FGFR inhibitors on synovial sarcoma cell lines were investigated in vitro and in vivo. RESULTS: Synovial sarcoma cell lines expressed multiple FGF genes especially those expressed in neural tissues, among which FGF8 showed growth stimulatory effects in all synovial sarcoma cell lines. FGF signals in synovial sarcoma induced the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and p38MAPK but not c-Jun NH2-terminal kinase. Disruption of the FGF signaling pathway in synovial sarcoma by specific inhibitors of FGFR caused cell cycle arrest leading to significant growth inhibition both in vitro and in vivo. Growth inhibition by the FGFR inhibitor was associated with a down-regulation of phosphorylated ERK1/2 but not p38MAPK, and an ERK kinase inhibitor also showed growth inhibitory effects for synovial sarcoma, indicating that the growth stimulatory effect of FGF was transmitted through the ERK1/2. CONCLUSIONS: FGF signals have an important role in the growth of synovial sarcoma, and inhibitory molecules will be of potential use for molecular target therapy in synovial sarcoma.

Animals↗

PubMed2005

Reappraisal of surgical treatment for radiation enteritis.

Although radiation enteritis is a well-recognized sequel of therapeutic irradiation, the standard surgical method is not universally agreed upon. Not only the short-term effect but also the long-term effect after a surgical intervention has been fairly well reported. To reassess the surgical therapy for radiation enteritis, we retrospectively analyzed 48 patients (5 males and 43 females, mean age 58.6 years) who had been operated on in our department. These patients were divided into two types according to the time of surgery or the clinical manifestation, and operative methods were analyzed. Patient's status such as bowel movement, body weight, and serum albumin value after surgery were analyzed, together with the patients survival. Our surgical methods were small intestinal resection for the intestinal obstruction, and pull-through reconstruction for proctitis. Two patients died of multiple organ failure caused by perforated peritonitis irrespective of emergent operation. Although the overall morbidity was 21.7%, there was no leakage when bowels were anastomosed. Overall survival after radiation-related complication in patients without previous neoplastic disease recurrence was 89%, 79%, and 69%, at 1, 3, and 5 years after surgery, respectively. Bowel motility, serum albumin level, and body weight recovered gradually soon after the operation and reached satisfactory levels within 6 months. Our analysis showed that small bowel injury should be treated by generous resection of the affected bowel followed by careful anastomosis of the disease-free ends, while rectal resection is best dealt with by restorative proctectomy. This may provide a good quality of life and minimize major postoperative complications such as leakage.

Adult↗

PubMed2004

A library of spirooxindoles based on a stereoselective three-component coupling reaction.

A collection of structurally complex and chemically diverse small molecules is a useful tool to explore cell circuitry. In this article, we report the split-pool synthesis of more than 3000 spirooxindoles on high capacity macrobeads. The key reaction to assemble the spirooxindole core stereoselectively is a Lewis acid variant of the Williams' three-component coupling. After formation, the skeleton was elaborated using Sonogashira couplings, amide forming reactions, and N-acylations of gamma-lactams. The final library was analyzed by sampling individual macrobeads and by using binomial confidence limits. It was determined that at least 82% of the library compounds should have better than 80% purity. To demonstrate the utility of our discovery process, a high-throughput chemical genetic modifier screen was performed using stock solutions of the resultant products. A number of positives were identified as enhancers of the cellular actions of latrunculin B, an actin polymerization inhibitor. Through resynthesis, we confirmed one of the positives and demonstrated that, in yeast cells, it has an EC50 in the sub-micromolar range.

Aldehydes↗

PubMed2004

PGE2 signal through EP2 promotes the growth of articular chondrocytes.

UNLABELLED: EP2 was identified as the major PGE2 receptor expressed in articular cartilage. An EP2 agonist increased intracellular cAMP in articular chondrocytes, stimulating DNA synthesis in both monolayer and 3D cultures. Hence, the EP2 agonist may be a potent therapeutic agent for degenerative cartilage diseases. INTRODUCTION: Prostaglandin E2 (PGE2) exhibits pleiotropic effects in various types of tissue through four types of receptors, EP1-4. We examined the expression of EPs and effects of agonists for each EP on articular chondrocytes. MATERIALS AND METHODS: The expression of each EP in articular chondrocytes was examined by immunohistochemistry and RT-PCR. A chondrocyte cell line, MMA2, was established from articular cartilage of p53(-/-) mice and used to analyze the effects of agonists for each EP. A search for molecules downstream of the PGE2 signal through the EP2 agonist was made by cDNA microarray analysis. The growth-promoting effect of the EP2 agonist on chondrocytes surrounded by cartilage matrix was examined in an organ culture of rat femora. RESULTS AND CONCLUSION: EP2 was identified as the major EP expressed in articular cartilage. Treatment of MMA2 cells with specific agonists for each EP showed that only the EP2 agonist significantly increased intracellular cAMP levels in a dose-dependent manner. Gene expression profiling of MMA2 revealed a set of genes upregulated by the EP2 agonist, including several growth-promoting and apoptosis-protecting genes such as the cyclin D1, fibronectin, integrin alpha5, AP2alpha, and 14-3-3gamma genes. The upregulation of these genes by the EP2 agonist was confirmed in human articular chondrocytes by quantitative mRNA analysis. On treatment with the EP2 agonist, human articular chondrocytes showed an increase in the incorporation of 5-bromo-2-deoxyuracil (BrdU), and the organ culture of rat femora showed an increase of proliferating cell nuclear antigen (PCNA) staining in articular chondrocytes surrounded by cartilage matrix, suggesting growth-promoting effects of the PGE2 signal through EP2 in articular cartilage. These results suggested that the PGE2 signal through EP2 enhances the growth of articular chondrocytes, and the EP2 agonist is a candidate for a new therapeutic compound for the treatment of degenerative cartilage diseases.

Adult↗

PubMed2004

Brain metastasis from colorectal cancer.

PURPOSE: The mechanism of brain metastasis is not well understood, but the affinity between cancer cells and neural tissues may be involved in the process. The aim of our study is to elucidate the involvement of neural cell adhesion molecule (NCAM) and therapeutic parameters in patients with brain metastasis from colorectal cancer. METHODS: We retrospectively identified 17 patients with brain metastasis from colorectal cancer. Data were collected with regard to patients' characteristics, location, and stage of primary tumor, and extent and location of metastatic disease. NCAM histochemical staining was undertaken using a paraffin block, and compared with 56 Dukes C patients and 13 Dukes D patients. RESULTS: Neural cell adhesion molecule expression was significantly higher in the primary tumors of the brain metastasis patients than in the lesions of the Dukes C and Dukes D control groups (p = 0.0004). Patients whose tumor was managed by radiosurgery survived longer than patients who had had whole brain radiation or those who had been left untreated. CONCLUSION: The fact that NCAM expression was high in the primary tumors of brain metastasis patients suggests that the affinity of cancer cells to a particular organ is important for circulation-mediated metastasis. Controlling local tumors using radiosurgery is certainly going to play an important role in extending survival and improving the patient's quality of life (QOL).

Adult↗

PubMed2004

Identification of PDZK4, a novel human gene with PDZ domains, that is upregulated in synovial sarcomas.

In an earlier study designed to investigate molecular mechanisms of carcinogenesis in synovial sarcomas (SSs), we applied a cDNA microarray to detect human genes with significantly increased expression in SS cells. Among the genes selected in this way, we identified a novel transcript, subsequently designated PDZK4 (PDZ domain-containing 4), that was specifically upregulated in all of the 13 SS cases we examined. On Northern blots of normal human tissues, the PDZK4 transcript was expressed only in fetal brain. Immunocytochemical staining of transfected COS7 cells showed that the PDZK4 gene product localized mainly under the plasma membrane. Treatment of human SS cells with small interfering RNA (siRNA) inhibited the expression of PDZK4 and resulted in the suppression of tumor-cell growth. Induction of exogenous PDZK4 expression promoted growth of T98G and COS7 cells in which no endogenous expression of PDZK4 was observed. Taken together, these findings strongly suggest that inappropriate expression of PDZK4 might play an important role in the proliferation of SS cells and that the gene might be a suitable molecular target for designing of novel drugs to treat SS patients.

Base Sequence↗

PubMed2004

Weakness of anastomotic site in diabetic rats is caused by changes in the integrity of newly formed collagen.

AIMS: Diabetes mellitus often causes anastomotic leakage leading to severe complications after surgery. The purpose of this study was to determine whether collagen synthesis is correlated with the anastomotic strength in diabetic animals in special reference to collagen type differences. METHODS: Thirty Lewis rats weighing approximately 250 g were made diabetic by tail vein injection of streptozotocin (STZ). Laparotomy was performed through a midline incision under ether anesthesia. A colonic segment 5 cm distal to the ileocecal junction was transected then anastomosed with absorbable suture. Anastomotic strength was measured on days 3, 5, 7 and 14 postoperatively, and compared with normal rats. Collagen type I and type III mRNA together with the total collagen concentration were measured in anastomotic sites. RESULTS: Anastomotic strength in diabetic rats was significantly lower on day 7, but gradually recovered up to day 14. There was no statistical significance between the two groups in hydroxyproline concentrations. Although the expressions of mRNA of collagen type III in both groups were statistically not different, that of collagen type I in the diabetes group merely increased and was clearly less than that of the control group. CONCLUSIONS: Anastomotic integrity in diabetic rats was significantly damaged on day 7 after surgery but recovered by day 14. This is caused not by the total contents of collagen accumulation but by the decrease of newly formed collagen type I contents.

Anastomosis, Surgical↗

PubMed2004

Methylation in the core-promoter region of the chondromodulin-I gene determines the cell-specific expression by regulating the binding of transcriptional activator Sp3.

Transcriptional regulation of cell- and stage-specific genes is a crucial process in the development of mesenchymal tissues. Here we have investigated the regulatory mechanism of the expression of the chondromodulin-I (ChM-I) gene, one of the chondrocyte-specific genes, in osteogenic cells using osteosarcoma (OS) cells as a model. Methylation-specific sequence analyses revealed that the extent of methylation in the core-promoter region of the ChM-I gene was correlated inversely with the expression of the ChM-I gene in OS primary tumors and cell lines. 5-Aza-deoxycytidine treatment induced the expression of the ChM-I gene in ChM-I-negative OS cell lines, and the induction of expression was associated tightly with the demethylation of cytosine at -52 (C(-52)) in the middle of an Sp1/3 binding site to which the Sp3, but not Sp1, bound. The replacement of C(-52) with methyl-cytosine or thymine abrogated Sp3 binding and also the transcription activity of the genomic fragment including C(-52). The inhibition of Sp3 expression by small interfering RNA reduced the expression of the ChM-I gene in ChM-I-positive normal chondrocytes, indicating Sp3 as a physiological transcriptional activator of the ChM-I gene. These results suggest that the methylation status of the core-promoter region is one of the mechanisms to determine the cell-specific expression of the ChM-I gene through the regulation of the binding of Sp3.

5-Methylcytosine↗

PubMed2004

Expression of the chondromodulin-I gene in chondrosarcomas.

We investigated the expression of the Chondromodulin-I (ChM-I) gene, a putative tumor suppressor gene in cartilaginous tumors, by quantitative RT-PCR in 15 chondrosarcomas (CSs). Eight CSs expressed the ChM-I gene at the level higher than those in articular cartilage (positive cases), whereas the expression of the ChM-I gene in the remaining seven CSs was lower than those in articular cartilage (negative cases). All of five peripheral CS were positive, and the ChM-I positive tumors shared expression profiles of cartilage-related genes with articular cartilage cells. On the other hand, all of four central CSs without extramedullary lesions were negative, and the ChM-I negative tumors expressed the parathyroid hormone-related peptide gene at the lower level and the COL10A1 genes at the higher level than articular cartilage cells. Neither the histological grade nor the rate of recurrence showed clear association with the level of ChM-I gene expression. These results suggested that the expression of ChM-I gene in CS has no direct role in tumorigenesis but rather reflects the site of tumor development and therefore precursor of tumor cells.

Aggrecans↗

PubMed2004

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

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

Adolescent↗

PubMed2003

Catalytic asymmetric aldol reactions in aqueous media using chiral bis-pyridino-18-crown-6-rare earth metal triflate complexes.

Catalytic asymmetric aldol reactions in aqueous media have been developed using Pr(OTf)(3) and chiral bis-pyridino-18-crown-6 1. In the asymmetric aldol reaction using rare earth metal triflates (RE(OTf)(3)) and 1, slight changes in the ionic diameters of the metal cations greatly affected the diastereo- and enantioselectivities of the products. The substituents (MeO, Br) at the 4-position of the pyridine rings of the crown ether did not significantly affect the selectivities in the asymmetric aldol reaction, although they affected the binding ability of the crown ether with RE cations and the catalytic activity of Pr(OTf)(3)-crown ether complexes. From X-ray structures of RE(NO(3))(3)-crown ether complexes, it was found that they had similar structures regardless of the RE cations and the crown ethers used. Accordingly, the binding ability of the crown ether with the RE cation and the catalytic activity of the complex are important for attaining high selectivity in the asymmetric aldol reaction. Various aromatic and alpha,beta-unsaturated aldehydes and silyl enol ethers derived from ketones and a thioester can be employed in the catalytic asymmetric aldol reactions using Pr(OTf)(3) and 1, to provide the aldol adducts in good to high yields and stereoselectivities. In the case using the silyl enol ether derived from the thioester, 2,6-di-tert-butylpyridine significantly improved the yields of the aldol adducts.

Journal Article↗

PubMed2002

Mutation analyses of the NFAT1 gene in chondrosarcomas and enchondromas.

Mice lacking nuclear factor of activated T cell 1 (NFAT1) showed an abnormal proliferation of chondrocytes in articular cartilage and formed an extraosseous cartilaginous mass resembling a neoplastic lesion, suggesting that the NFAT1 gene is a tumor suppressor gene in cartilaginous neoplasms. Here we performed mutation analyses of the NFAT1 gene in human cartilaginous tumors including 30 chondrosarcomas and 15 enchondromas. Reverse transcription-polymerase chain reaction (PCR) analysis revealed the expression of the NFAT1 gene in 15/15 chondrosarcomas and 12/13 enchondromas. To find subtle alterations, the genomic structure of the NFAT1 gene was determined using human genome draft sequences, and a mutation analysis was performed using the exon-by-exon PCR-single-strand conformation polymorphism method. Two heterozygous missense mutations, A1557T (His446Leu) and C2859T (Pro880Leu), were found in eight tumor samples, but the same mutation was also present in the constitutional cells of corresponding patients. The incidence of the mutant alleles in the patient and control groups showed no significant difference, suggesting that these mutations are rare single nucleotide polymorphisms unrelated with tumorigenesis. These results suggest that the NFAT1 gene is not likely to be a tumor suppressor gene in human cartilaginous tumors.

Adolescent↗

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↗