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Hiroshi Horie

Publications and source records attributed to Hiroshi Horie.

15 recordsLinked to original sources
PubMed2007

Reciprocal expression of CCAAT/enhancer binding proteins alpha and beta in hepatoblastomas and its prognostic significance.

Hepatoblastoma is one of the common pediatric solid tumors with frequent mutation of the beta-catenin gene which might be an early event of its carcinogenesis. However, the detailed molecular mechanism is still unknown. We studied the expression levels of CCAAT/enhancer binding protein alpha (C/EBPalpha) and C/EBPbeta, which regulate differentiation and growth of embryonic hepatocytes, to establish whether or not they were involved in affecting the clinical behavior of hepatoblastoma. The quantitative real-time reverse transcriptase-PCR revealed that expression of C/EBPalpha mRNA was significantly up-regulated in tumors 223% (p=0.013) as compared with that in adjacent normal livers, while expression of C/EBPbeta was down-regulated to 27% (p=0.002). Of interest, the immunohistochemical analysis showed that expression of C/EBPalpha was higher and that of C/EBPbeta lower in the poorly differentiated tumor cells than in the well-differentiated cells within the same tumor. Furthermore, high expression of C/EBPalpha (p=0.047) as well as low expression of C/EBPbeta (p=0.025) was significantly associated with poor prognosis of the patients. Cox hazard model suggested that expression of C/EBPalpha and that of C/EBPbeta were independent indicators to predict the prognosis from age but not from histology. Thus, expression of C/EBP proteins may play an important role in the genesis and clinical behavior of hepatoblastoma probably by inducing different stages of arrest of differentiation.

CCAAT-Enhancer-Binding Protein-alpha↗
PubMed2006

The perinatal transition of the hepatobiliary cyst size provides information about the condition of bile flow in biliary cystic malformation cases.

PURPOSE: The aim of this study was to understand the level of bile flow by perinatal transitions of the hepatobiliary cyst size in biliary cystic malformation (BCM) cases and to examine the association between the transitions of the cyst size, cholangiographic images of the intrahepatic bile ducts (IHBDs), and histological features of the liver specimens in BCM. METHODS: We measured perinatal size of the hepatobiliary cyst in 7 BCM cases, composed of 1 case with choledochal cyst and 6 cases with biliary atresia (BA). Bile excretion was inferred from the transition of cyst size and the postoperative course. The IHBD cholangiographic images were also examined. In addition, histology of liver specimens obtained at the time of initial surgery was evaluated for IHBD maturity and fibrosis. RESULTS: The size of the small cyst in 2 BA cases remained almost unchanged throughout gestation. These cases required longer postoperative period for the clearance of jaundice. Their IHBD images were indistinct, and histology showed severe fibrosis. The ratio of bile ducts to portal tracts was 0.5 in 1 of the cases. However, in other BCM cases where the cysts grew large perinatally, bile excretion was good postoperatively, and their jaundice cleared in shorter period. Their cholangiographic images demonstrated clearer periphery of the IHBDs, and their histology showed mild or moderate fibrosis, if any. CONCLUSIONS: The perinatal transition of the cyst size in BCM cases can be helpful in assessing the level of bile flow. BCM with a small cyst during gestation can include some BAs with poorer bile flow, vaguer IHBD images, and prominent liver fibrosis. For the treatment of BCM cases, especially patients with a small biliary cyst, prompt response may be required after birth.

Bile↗
PubMed2005

Expression pattern of keratin subclasses in pancreatoblastoma with special emphasis on squamoid corpuscles.

Expression patterns of keratins (K), both simple epithelia-type (K7, K8, K18, K19) and complex/stratified epithelia-type (K1, K4, K5/6, K10, K13, K14, K15, K16, K17), and epithelial membrane antigen (EMA) were immunohistochemically studied in six pancreatoblastomas (PBL). In all six tumors, areas with overt acinar differentiation (AA), solid areas without any specific differentiation (SO), and squamoid corpuscles (SC) were diffusely positive for K8, K18, and K19. The AA and SO in all the tumors were diffusely positive for K7, but the SC were negative or displayed only scattered reactivity for K7. In three tumors, the AA and the SC showed scattered reactivity for K5/6. No reactivity for other complex/stratified epithelia-type K was found in any of the examined tumor. All tumors were reactive for EMA with consistent predominancy in the SC. Ultrastructurally, well-developed desmosome-tonofilament complexes were only partially observed in tumor cells comprising the SC. These results implied that (i) the SC usually lack a character of complete squamous metaplasia; and (ii) the SC have a characteristic phenotype (K8/K18/K19/EMA-positive, K7-negative or scatteredly positive) that can potentially be useful to delineate the SC in PBL.

Child↗
PubMed2004

Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas.

Hepatoblastoma is one of the most common malignant liver tumors in young children. Recent evidences have suggested that the abnormalities in Wnt signaling pathway, as seen in frequent mutation of the beta-catenin gene, may play a role in the genesis of hepatoblastoma. However, the precise mechanism to cause the tumor has been elusive. To identify novel hepatoblastoma-related genes for unveiling the molecular mechanism of the tumorigenesis, a large-scale cloning of cDNAs and differential screening of their expression between hepatoblastomas and the corresponding normal livers were performed. We constructed four full-length-enriched cDNA libraries using an oligo-capping method from the primary tissues which included two hepatoblastomas with high levels of alpha-fetoprotein (AFP), a hepatoblastoma without production of AFP, and a normal liver tissue corresponded to the tumor. Among the 10,431 cDNAs randomly picked up and successfully sequenced, 847 (8.1%) were the genes with unknown function. Of interest, the expression profile among the two subsets of hepatoblastoma and a normal liver was extremely different. A semiquantitative RT-PCR analysis showed that 86 out of 1188 genes tested were differentially expressed between hepatoblastomas and the corresponding normal livers, but that only 11 of those were expressed at high levels in the tumors. Notably, PLK1 oncogene was expressed at very high levels in hepatoblastomas as compared to the normal infant's livers. Quantitative real-time RT-PCR analysis for the PLK1 mRNA levels in 74 primary hepatoblastomas and 29 corresponding nontumorous livers indicated that the patients with hepatoblastoma with high expression of PLK1 represented significantly poorer outcome than those with its low expression (5-year survival rate: 55.9 vs 87.0%, respectively, p=0.042), suggesting that the level of PLK1 expression is a novel marker to predict the prognosis of hepatoblastoma. Thus, the differentially expressed genes we have identified may become a useful tool to develop new diagnostic as well as therapeutic strategies of hepatoblastoma.

Cell Cycle Proteins↗
PubMed2003

Significance of aberrant (cytoplasmic/nuclear) expression of beta-catenin in pancreatoblastoma.

This study concerns the significance of aberrant (nuclear/cytoplasmic) expression of beta-catenin in pancreatoblastoma (PBL). On immunohistochemistry, all seven PBLs examined showed nuclear/cytoplasmic expression of beta-catenin, predominantly in the squamoid corpuscles (SCs). In areas with acinar/ductular differentiation, few tumour cells displayed nuclear/cytoplasmic expression of beta-catenin and more than half of the tumour cells showed membranous expression. Two out of five (40%) tumours examined showed missense mutations in codons 33 and 37 of exon 3 of the beta-catenin gene. No mutation of the adenomatous polyposis coli (APC) gene was detected in two of the remaining three tumours. Amplifiable DNA for APC analysis was not obtained from the one other tumour. Immunoreactivity for cyclin D1, one of the nuclear targets of beta-catenin, was found predominantly in the SCs of the seven tumours. In contrast, the Ki-67 labelling index was 2-4% (median 3%) in the SCs and 8-18% (median 12%) in the other areas, indicating a negative correlation with nuclear cyclin D1 reactivity. These results imply that in PBLs, nuclear/cytoplasmic accumulation of beta-catenin and overexpression of its target gene cyclin D1 are not associated with the induction of tumour cell proliferation. Nuclear/cytoplasmic accumulation of beta-catenin may be related to the morphogenesis of the SCs that are considered most characteristic for PBL.

Child↗
PubMed2003

Nephron-sparing surgery for multilocular cyst of the kidney in a child.

Multilocular cyst of the kidney is an uncommon benign renal neoplasm. Because of its benign nature, this lesion is best managed by nephron-sparing surgery. This report describes a child who underwent a partial nephrectomy for a multilocular cyst of the kidney. After reviewing other cases, we discuss the clinical characteristics of multilocular cyst of the kidney and emphasize the cystic partially differentiated nephroblastoma as a differential diagnosis.

Child↗
PubMed2003

Fatal infectious mononucleosis with evidence suggestive of the development of B cell lymphoma.

A 4-year-old girl presented to a local hospital in August 1999 with fever and cervical lymphadenopathy. A diagnosis of Epstein-Barr virus (EBV) infection was made and the patient was treated with corticosteroids. One month later she developed dyspnea secondary to tonsilar swelling, and underwent tonsillectomy and adenoidectomy. Her dyspnea increased, however, and by mid September she required mechanical ventilation. Six weeks later, she was transferred to Chiba Children's Hospital (Chiba, Japan). Despite vigorous treatment, she died within four weeks of admission. At autopsy, microscopic examination revealed numerous histiocytes with frequent hemophagocytosis in her lungs, liver, spleen, thymus, and lymph nodes. The tentative diagnosis was EBV-associated hemophagocytic syndrome (EBVAHS). A proliferation of atypical lymphocytes was observed in the lymph nodes, the majority of which stained positive with CD79a antibody. A whitish nodule, 8 mm in diameter, was noted in her right ovary. It consisted of a proliferation of pleomorphic lymphoid cells expressing CD79a antigen. In situ hybridization detected EBV RNA within CD79a antigen-positive cells in the lungs, spleen, thymus, bone marrow, lymph nodes, and the right ovary. Polymerase chain reaction analysis of DNA from the ovarian nodule demonstrated a monoclonal rearrangement of the immunoglobulin heavy chain gene indicating that it consisted of a clone of B lymphocytes. We suggest that EBVAHS develops into polyclonal and monoclonal lymphoproliferative disorder in a short period, and that EBVAHS is a preneoplastic condition that may result in B cell lymphoma.

Adenoidectomy↗
PubMed2002

Paraovarian cyst with torsion in children.

Paraovarian cyst is very uncommon in children, and its preoperative diagnosis is difficult. This report describes 2 cases of surgically proven paraovarian cyst with torsion. It is important to be aware of torsion as a complication of paraovarian cyst.

Adolescent↗
PubMed2002

Potter sequence complicated by congenital cystic lesion of the bladder.

We report a case complicated by oligohydramnios, pulmonary hypoplasia, bilateral renal dysplasia, and cystic lesion of the bladder. He was clinically compatible with Potter sequence. Congenital cystic bladder is the rarest form of the bladder. We can find no report of Potter sequence complicated by cystic lesion of the bladder. This lesion was similar to multilocular bladder. The diagnosis was confirmed it by autopsy, magnetic resonance imaging, and urography after his death.

Abnormalities, Multiple↗
PubMed2002

Report of a patient with a high level of parathyroid hormone-related peptide associated with malignant lymphoma involving multiple bony lesions.

Hypercalcemia in malignant lymphoma is not common. Our case of malignant lymphoma with multiple bony lesions showed hypercalcemia (13 mg/dl) at the time of bone marrow relapse. The serum level of parathyroid hormone-related peptide increased to 142 pmol/l, which may be secreted by malignant lymphoma cells. The course of the patient was aggressive and she died from bone marrow relapse after 6 months of treatment including high-dose methotrexate, which caused acute nonoliguric renal failure. At autopsy there was extensive calcium deposition in the lungs, kidneys and pancreas and prominent tubular damage of kidneys.

Antimetabolites, Antineoplastic↗
PubMed2002

[A case of FK 506-induced leukoencephalopathy].

We reported a 15-year-old boy with an acute myelomonocytic leukemia and FK 506-induced leukoencephalopathy. He was received FK 506 for graft versus host disease occurred after peripheral blood stem cell transplantation. He, four weeks later, had generalized seizures and consciousness disturbance. The serum level of FK 506 was high (27.5 ng/ml). His brain MRI showed abnormal high intensity areas in the frontal and parietal white matter lesions on T2-weighted images. Neuropathological studies revealed the destruction of myelin sheeths and axons in the cerebral white matter corresponded with abnormal lesions on MRI. There were calcification and mineralization in the small vessel walls of the cortex and white matter. Osteopontin immunoreactivity was detected in the endothelial cells of small vessels. These findings suggest that the vascular damage was involved in the FK 506-induced leukoencephalopathy.

Adolescent↗
PubMed2002

Correlation between nuclear action of anthracycline anticancer agents and their binding affinity to the proteasome.

4'-O-tetrahydropyranyladriamycin (THP) showed an approximately 10-fold greater inhibitory effect on DNA synthesis in L1210 mouse leukemia cells than adriamycin (ADM). The intracellular transfer rate and nuclear accumulation of THP were approximately 5-fold higher than those of ADM. The intensity of in vitro inhibition of topoisomerase II activity by ADM was almost the same as that by THP. There were no significant differences between the uptake of either of these agents by the isolated nuclei of L1210 cells. The nuclear uptake of both agents in the presence of the cytosolic fraction of L1210 cells consisted of both simple diffusion and carrier-mediated components, and the carrier-mediated component of THP was approximately 2-fold higher than that of ADM. THP showed approximately 5-fold higher affinity to the proteasome than ADM, and interfered with ADM binding in a competitive manner. These results suggest that the binding affinity of these anticancer agents to the proteasome is an important factor in their transport to the nucleus and determines their specificity of action for the nuclear DNA.

Active Transport, Cell Nucleus↗
PubMedDate not supplied

Ocular lesions in Watanabe heritable hyperlipidemic rabbits.

Hyperlipidemic ocular lesions are described for Watanabe heritable hyperlipidemic (WHHL) rabbits. Male WHHL rabbits 8 months old exhibited serum hyperlipidemia and ophthalmoscopically yellowish-white lesions along the corneoscleral junction and in the iris. Histopathologically, foamy macrophages aggregated in the stroma of the cornea, iris, and ciliary body were observed. These findings have been interpreted as lipid keratopathy. In addition, multiple clusters of a large number of foamy macrophages occurred throughout the choroid and sclera in association with the blood vessels. The lesions in the choroid and sclera could not be detected ophthalmoscopy, yet were much more prominent than those in the cornea, iris, and ciliary body, suggesting greater involvement and earlier onset of lipidosis at these sites associated with hyperlipidemia in WHHL rabbits.

Animals↗