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Yasuaki Nakashima

Publications and source records attributed to Yasuaki Nakashima.

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

A case of multifocal fibrosclerosis with intracardiac solid masses.

We report an extremely rare case of multifocal fibrosclerosis (MFS) with intracardiac solid masses. A 70-year-old woman with Hashimoto's disease had pericardial thickening and intracardiac masses. Histology of pericardiectomy showed only fibrosis. The clinical diagnosis was constrictive pericarditis. She died of postoperative infectious mediastinitis and cerebral infarction. Postmortem examination revealed intracardiac solid masses contiguous to thickened pericardium. Multifocal areas of fibrosis were also seen in the pericardium, mediastinum, abdominal cavity, and the retroperitoneum. The intracardiac masses and the areas of fibrosis were composed of collagenous fibers with various intensities of inflammatory infiltrates and sclerotic changes. Neoplastic changes were not observed. These histological features were similar to that of MFS. The intracardiac masses are interpreted as one of the manifestations of MFS. This is the first case of MFS accompanied with intracardiac solid masses.

Aged↗
PubMed2006

Evaluation of primary brain tumors with FLT-PET: usefulness and limitations.

PURPOSE OF THE REPORT: The purpose of this report was to investigate the potential of positron emission tomography using F-18 fluorodeoxythymidine (FLT-PET) in evaluating primary brain tumors. MATERIALS AND METHODS: FLT-PET was performed in 25 patients with primary brain tumors. FLT uptake in the lesion was semiquantitatively evaluated by measuring the maximal standardized uptake value (SUVmax) and the tumor-to-normal tissue ratio (TNR). SUVmax and TNR were compared with the histologic grade and the expression of the proliferation marker (Ki-67). RESULTS: FLT uptake in normal brain parenchyma was very low, resulting in the visualization of brain tumors with high contrast. Both SUVmax and TNR significantly correlated with the malignant grade of brain gliomas, in which high SUVmax/TNR was obtained for high-grade gliomas. Patients with primary lymphoma also showed SUVmax/TNR equivalent to glioblastoma. There was a positive correlation between SUVmax/TNR and the Ki-67 index. In contrast, spuriously high SUVmax and TNR were obtained in 3 of 6 patients with suspected recurrent tumors (2 patients with recurrent grade 2 glioma and one patient with postoperative granuloma), all of which showed lesion enhancement on MRI after Gd administration. CONCLUSIONS: FLT-PET can be used to evaluate the malignant grade and proliferation activity of primary brain tumors, especially malignant brain tumors. However, the presence of benign lesions showing blood-brain barrier disruption cannot be distinguished from malignant tumors and needs to be carefully evaluated.

Adolescent↗
PubMed2006

Phase II study of nimustine, carboplatin, vincristine, and interferon-beta with radiotherapy for glioblastoma multiforme: experience of the Kyoto Neuro-Oncology Group.

OBJECT: This Phase II study was performed to determine the safety, tolerability, and efficacy of combining nimustine (ACNU)-carboplatin-vincristine-Interferon-beta (IFNbeta) chemotherapy. METHODS: Ninety-seven patients with Karnofsky Performance Scale scores of 50 or greater were enrolled in the study. Nimustine (60 mg/m2), carboplatin (110 mg/m2), vincristine (0.6 mg/m2), and IFNbeta (10 microg) were administered on Day 1 concomitant with radiotherapy (63 Gy); vincristine (0.6 mg/m2) and IFNbeta (10 microg) on Days 8 and 15; and IFNbeta alone (10 microg) three times per week throughout the course of radiotherapy. Fifty-six days after radiotherapy ended, the time schedule for chemotherapy was reset and ACNU, carboplatin, vincristine, and IFNbeta were again administered on the new Day 1 and vincristine and IFNbeta on the new Days 8 and 15. This course was repeated every 56 days. Instances of nonhematological toxicity were rare and mild. During the course of radiotherapy, the percentages of patients who experienced Grade 3 toxicity were 14% with neurocytopenia and 7% with thrombocytopenia. Seven percent of all adjuvant chemotherapy cycles following radiotherapy were associated with Grade 3 toxicity, as manifested in neurocytopenia or thrombocytopenia. No instance of Grade 4 toxicity was observed. The median duration of progression-free survival was 10 months (95% confidence interval [CI] 8-12 months) and the median duration of overall survival was 16 months (95% CI 13-20 months). CONCLUSIONS: The combination of ACNU-carboplatin-vincristine-IFNbeta chemotherapy and radiotherapy is safe and well tolerated, and may prolong survival in patients with glioblastoma multiforme.

Adult↗
PubMed2005

A case of autoimmune pancreatitis associated with sclerosing cholangitis, retroperitoneal fibrosis and Sjögren's syndrome.

We report a very rare case of autoimmune pancreatitis (AIP) associated with sclerosing cholangitis, retroperitoneal fibrosis and Sjögren's syndrome. The patient had an enlarged pancreas, and autoantibodies were detected in the serum. Serum IgG and IgG4 concentrations were also elevated. Endoscopic retrograde cholangiopancreatography revealed an irregular narrowing of the main pancreatic duct from the head to the body and sclerotic change in the intrapancreatic common bile duct, which later extended to the intrahepatic bile ducts. In addition, histological examination of the liver revealed lymphocytic sclerosis around the bile ducts, similar to the histology in the pancreas of AIP. Retroperitoneal tumors were diagnosed as retroperitoneal fibrosis by histological examination. Serological and functional abnormalities suggestive of Sjögren's syndrome were detected, and histological findings of the lip were compatible with Sjögren's syndrome. Immunohistochemistry of each lesion disclosed that most of the infiltrating lymphocytes were T cells with similar levels of both CD4+ and CD8+ cells. Moreover, some of the infiltrating plasma cells were positive for anti-IgG4 monoclonal antibody. These diseases were dramatically improved by steroid therapy. Although the pathophysiology of AIP is still unclear, the present case suggests a common pathophysiological mechanism for AIP, sclerosing cholangitis, retroperitoneal fibrosis and Sjögren's syndrome.

Aged↗
PubMed2005

Pulmonary sclerosing hemangioma with metastasis to the mediastinal lymph node.

During a routine health care evaluation, an abnormal shadow was detected in the chest roentgenogram of a 35-year-old man. Chest computed tomography scanning showed a nodule, approximately 3 cm in diameter, in the left S6 pulmonary segment with surrounding infiltration. Bronchoscopy revealed obstruction of the left B6c bronchus by a tumor, for which biopsy was done but no definitive histologic diagnosis could be made. Then, left lower lobectomy was performed, and the tumor was diagnosed as a pulmonary sclerosing hemangioma. A mediastinal lymph node (no. 7) showed some metastatic tumor cells. As lymph node metastasis from pulmonary sclerosing hemangioma is very rare, we herein report the details of our case.

Adult↗
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

The combination of mitotic and Ki-67 indices as a useful method for predicting short-term recurrence of meningiomas.

BACKGROUND: The most relevant factor in the progression-free survival (PFS) of patients with meningiomas is the malignant grade. However, using only the current World Health Organization (WHO) definition that does not consider precise quantitative indicators, an unequivocal diagnosis of the malignant grade is difficult. In our retrospective study of the PFS of meningioma patients, we focused on mitoses and the Ki-67 staining index of tumor specimens obtained at the initial surgery. METHODS AND RESULTS: A total of 349 patients with intracranial meningioma, operated between 1978 and 2000, were followed for a mean of 7 years. According to the mitotic index (MI), we classified them into 3 groups. In Group A (n = 326), slide-mounted tumor samples exhibited no mitoses; in Group B (n = 15) there were fewer than 4 mitoses, and in Group C (n = 8) 4 or more mitoses were seen per 10 high-power fields (HPF). The estimated 5-year PFS rates in Groups A, B, and C were 93%, 10%, and 13% respectively. The mean PFS for Group A was 148 months; in Groups B and C the median PFS was 43 and 16 months, respectively. A Ki-67 staining index (SI) of less than 1% corresponded with no mitosis, while an SI exceeding 5% was indicative of the presence of mitoses. CONCLUSION: In meningioma patients, no mitoses and/or a Ki-67 SI <1% signals a favorable outcome. An SI >5% or the presence of mitoses, even fewer than 4 in 10 HPF, is suggestive of a short PFS irrespective of other pathologic features. We suggest that in combination, assay of the Ki-67 SI and the MI represents a reliable, quantitative tool for predicting PFS in meningioma patients.

Adolescent↗
PubMed2003

Irritated seborrheic keratosis of the external ear canal.

Although a seborrheic keratosis is not rare on the skin of the trunk, extremities, head and neck of an elderly person, it is uncommon to originate in the external ear canal. Even rarer, an irritated subtype may arise in this location. We report the case of a 63-year-old man with an irritated seborrheic keratosis arising in the right external ear canal, who first presented with a bloody discharge from his right ear canal 3 years and 10 months before the subsequent operation. Macroscopically, a dome-like, black elevation was found at the anterior wall of the right external ear canal. A biopsy showed an exophytic papillomatous, hyperkeratotic growth of basaloid cells which revealed some nuclear atypism and mitosis. Squamous eddies and moderate inflammatory infiltrate were noted. Some cellular atypism made us suspect an irritated seborrheic keratosis. Because the patient hated the extirpation, he remained untreated for 3 years and 3 months following his first presentation. The biopsy and a surgical resection of his second presentation confirmed the diagnosis of irritated seborrheic keratosis. Immunohistochemical analysis of Ki-67, p53 and papillomavirus was performed to elucidate its character. We emphasize that irritated seborrheic keratosis does occur in the external ear canal and may cause some diagnostic difficulty. Pathologists should be aware of this fact and avoid overdiagnosis.

Ear Canal↗
PubMed2003

Immunohistochemical analysis of retroperitoneal Müllerian cyst.

Retroperitoneal cysts are uncommon diseases, and benign nonneoplastic Müllerian cysts are extremely rare among the known cases. We report a case of a 35-year-old woman with a retroperitoneal Müllerian cyst with the tubal type of epithelium. The patient presented with a large (20 cm in diameter), palpable abdominal mass. This multilocular cystic mass was resected from the retroperitoneum between the descending colon and the left renal fascia. Histologically, it was lined by monolayered low-cuboidal to columnar cells without atypia that resembled tubal epithelium, including cilia. Loose fibrous tissue and incomplete smooth muscle bundles were identified beneath the epithelium of the lining. Immunohistochemical tests showed that the lining cells were strongly positive for cytokeratins (CKs) (polyclonal, 7, 18, CAM 5.2, AE1/AE3), epithelial membrane antigen, cancer antigen 125, progesterone receptor, and estrogen receptor. The lining cells were also occasionally weakly positive for CK5/6. They tested negative for CK20, carcinoembryonic antigen, calretinin, and CD 10.

Adult↗
PubMed2003

Clear cell carcinoid tumor of the gallbladder. A case without von Hippel-Lindau disease.

A golden yellow polyp was detected in the gallbladder of a 64-year-old man who presented with epigastric pain. The lesion was composed of clear polygonal cells arranged in a trabecular and glandular pattern. The tumor invaded through the wall into the perimuscular subserosal layer. Immunohistochemical stains showed that neoplastic cells were positive for chromogranin A, synaptophysin, somatostatin, gastrin, and pancreatic polypeptide and negative for glucagon, serotonin, insulin, S100 protein, and inhibin. This tumor resembles the recently described clear cell endocrine tumors of the gallbladder and pancreas that are associated with von Hippel-Lindau disease. Our patient, however, had neither personal nor family history indicative of von Hippel-Lindau disease. Furthermore, published accounts of clear cell endocrine tumors in von Hippel-Lindau disease describe immunoreactivity for inhibin; the current case was negative for the disease. There may be a subtype of clear cell carcinoid tumor not associated with von Hippel-Lindau disease, which is characterized by its lack of immunoreactivity against inhibin.

Carcinoid Tumor↗