研究者詳細 - 一宮　慎吾

Misc - 一宮　慎吾

分割表示 112 件中 81 - 100 件目／全件表示 >>

臨床報告眼窩内に発生したsolitary fibrous tumorの1例

中村靖, 大塚賢二, 橋本雅人, 一宮慎吾, 佐藤昌明

臨床眼科 ( 株式会社医学書院 ) 53 ( 6 ) 1381 - 1384 1999年06月

Mutational analysis of the p73 gene in human breast cancers

T Shishikura, S Ichimiya, T Ozaki, Y Nimura, H Kageyama, Y Nakamura, S Sakiyama, M Miyauchi, N Yamamoto, M Suzuki, N Nakajima, A Nakagawara

INTERNATIONAL JOURNAL OF CANCER ( WILEY-LISS ) 84 ( 3 ) 321 - 325 1999年06月

In primary breast cancer, mutations of the p53 tumor suppressor gene lead to loss of growth-suppressive properties and poor outcome. Recently, a p53-related gene, termed p73, has been cloned and its gene product possesses a function similar to p53. p73 has been mapped at chromosome 1p36.3, a region frequently deleted in breast cancer, neuroblastoma and other malignancies. To elucidate the functional significance of p73 in the oncogenesis of breast cancer, we have studied genetic alterations of p73 in tissue specimens obtained from 87 patients with primary breast cancer. Thirteen percent of informative cases showed loss of heterozygosity (LOH) at the p73 gene. However, there was no correlation between the p73 LOH and clinical features such as histopathological types, metastatic behavior or expression of estrogen or progesterone receptor. The levels of p73 transcript in primary breast cancer were not significantly different from those in normal breast tissue. Moreover, PCR-SSCP analysis failed to detect any missense or frameshift mutations in the p73 gene. Our observations suggest that allelic loss, expression levels and mutations of the p73 gene may not contribute to oncogenesis of primary breast cancers. Int. J. Cancer (Pred. Oncol.) 84:321-325, 1999. (C) 1999 Wiley-Liss, Inc.

DOI PubMed CiNii

Identification of a transactivation activity in the COOH-terminal region of p73 which is impaired in the naturally occurring mutants found in human neuroblastomas

N Takada, T Ozaki, S Ichimiya, S Todo, A Nakagawara

CANCER RESEARCH ( AMER ASSOC CANCER RESEARCH ) 59 ( 12 ) 2810 - 2814 1999年06月

p73 is a recently cloned tumor suppressor gene that is highly homologous to p53, and the products of both possess similar functions in inhibiting cell growth and inducing apoptosis. Interestingly, the COOH-terminal region of p53 displays no significant homology with that of p73, Moreover, p73 has an additional segment at its COOII terminus. Recently, we have found two mutations of p73 with amino acid substitution (P405R and P425L) in primary neuroblastomas, Because the region (amino acid residues 382-491) contains a glutamine- and proline-rich domain, we hypothesized that it has a transactivation function, and the mutations found in tumors result in loss of function. To test it, we used the yeast GAL4 DNA-binding fusion system. Yeast transformants expressing a GAL4-p73(1-112) or a GAL4-p73 alpha(380-513) fusion protein were grown in SD medium lacking histidine and tryptophan and exhibited a significant induction of P-galactosidase activity, Transient transfection experiments revealed that both of fusion proteins could induce the chloramphenicol acetyltransferase activity in mammalian cells, indicating that the COOH-terminaI as well as NH2-terminal regions of p73 had significantly high levels of transactivation activity. Furthermore, the former activity was severely impaired in two naturally occurring mutant forms found in neuroblastomas. These suggest that, unlike p53, p73 has two domains with transactivation function, one in the NH2-terminal region and the other in the COOH-terminal region. Loss of function mutation in the latter might he involved in tumorigenesis and/or tumor progression.

神経線維腫症を伴わない多発性眼窩部神経線維腫の1例

中村靖, 大塚賢二, 橋本雅人, 一宮慎吾, 佐藤昌明

あたらしい眼科 = Journal of the eye 16 ( 2 ) 283 - 285 1999年02月

CiNii

O-334 p53 co-activator, p33^<ING1>の神経芽腫発生における役割 : 発現および変異とp53, mdm2との関連について

高橋將人, 一宮慎吾, 藤堂省

日本外科学会雑誌 ( 一般社団法人日本外科学会 ) 100 ( 0 ) 191 - 191 1999年02月

CiNii

P-804 肺癌における、p53関連遺伝子p73の変異および欠失と、その臨床的意義

山本直敬, 飯島崇利, 一宮慎吾, 影山肇, 木村秀樹, 中川原章

日本外科学会雑誌 ( 一般社団法人日本外科学会 ) 100 ( 0 ) 512 - 512 1999年02月

CiNii

Absence of mutation of the p73 gene localized at chromosome 1p36.3 in hepatocellular carcinoma

M Mihara, Y Nimura, S Ichimiya, S Sakiyama, S Kajikawa, W Adachi, J Amano, A Nakagawara

BRITISH JOURNAL OF CANCER ( CHURCHILL LIVINGSTONE ) 79 ( 1 ) 164 - 167 1999年01月

Accumulating evidence has demonstrated that aberration of the p53 tumour-suppressor gene is one of the pivotal genetic events in hepatocellular carcinogenesis. Recent reports suggest that the product of hepatitis B virus (HBV) interacts with p53 and that the hepatitis C virus (HCV) core protein reduces p53 expression. A novel p73 gene, which is related to p53, has recently been identified and mapped to chromosome 1 p36.3, which is a locus of multiple tumour-suppressor genes for many cancers, including hepatocellular carcinoma (HCC) and neuroblastoma. Here, we investigated mRNA expression, allelotype and mutation of p73 in 48 HCCs obtained from untreated patients. Reverse transcriptase polymerase chain reaction (RT-PCR) revealed that p73 mRNA was expressed ubiquitously at low levels in all the tumour tissues, as well as in the adjacent normal liver tissues. The frequency of p73 loss of heterozygosity was observed in 20% of HCCs, but PCR-single strand conformation polymorphism (SSCP) analysis showed no mutations in the 48 tumours except for three types of polymorphisms. These results suggest that p73 may play a role in hepatocellular carcinogenesis in a different manner from a Knudson two-hit model. The regulatory mechanism of interaction between p73 and hepatitis viruses remains to be determined.

DOI PubMed CiNii

p73 at chromosome 1p36.3 is lost in advanced stage neuroblastoma but its mutation is infrequent

S Ichimiya, Y Nimura, H Kageyama, N Takada, M Sunahara, T Shishikura, Y Nakamura, S Sakiyama, N Seki, M Ohira, Y Kaneko, F McKeon, D Caput, A Nakagawara

ONCOGENE ( STOCKTON PRESS ) 18 ( 4 ) 1061 - 1066 1999年01月

p73, a novel p53 family member, is a recently identified candidate neuroblastoma (NBL) suppressor gene mapped at chromosome 1p36.33 and was found to inhibit growth and induce apoptosis in cell lines. To test the hypothesis that p73 is a NBL suppressor gene, we analysed the p73 gene in primary human NBLs, Loss of heterozygosity (LOH) for p73 was observed in 19% (28/151) of informative cases which included 92 mass-screening (MS) tumors. The high frequency of p73 LOH was significantly associated with sporadic NBLs (9% vs 34%, P < 0.001), N-myc amplification (10% vs 71%, P < 0.001), and advanced stage (14% vs 28%, P < 0.05), Both p73 alpha and p73 beta transcripts were detectable in only 46 of 134 (34%) NBLs at low levels by RT-PCR methods, while they were easily detectable in most breast cancers and colorectal cancers under the same conditions. They found no correlation between p73 LOH and its expression levels (P > 0.1), We found two mutations out of 140 NBLs, one somatic and one germline, which result in amino acid substitutions in the C-terminal region of p73 which may affect transactivation functions, though, in the same tumor samples, no mutation of the p53 gene was observed as reported previously. These results suggest that allelic loss of the p73 gene may be a later event in NBL tumorigenesis. However, p73 is infrequently mutated in primary NBLs and may hardly function as a tumor suppressor in a classic Knudson's manner.

DOI PubMed CiNii

p73, a gene related to p53, is not mutated in esophageal carcinomas

Y Nimura, M Mihara, S Ichimiya, S Sakiyama, N Seki, M Ohira, N Nomura, M Fujimori, W Adachi, J Amano, M He, YM Ping, A Nakagawara

INTERNATIONAL JOURNAL OF CANCER ( WILEY-LISS ) 78 ( 4 ) 437 - 440 1998年11月

A novel gene, termed p73, encodes a protein with a significant homology to p53 and has been mapped at chromosome 1p36.3, which is a locus of multiple suppressor genes for tumors including neuroblastoma and other cancers. Since the 1p36 locus is reported to be deleted and p53 is frequently mutated in esophageal carcinomas, we examined loss of heterozygosity (LOH) and mutation of the p73 gene in 48 untreated esophageal tumors, as well as mRNA expression in 8 tumors. We screened the pi genomic library to obtain a pi clone containing the p73 gene and found a polymorphic short tandem CT repeat site at intron 9, Intragenic sequences for 14 PCR primer sets and a primer pair flanking the repeat were also determined for the analysis of PCR single-strand conformation polymorphism (SSCP) and LOH studies, respectively, Expression of p73 mRNA was detectable but at low levels in all 8 tumor tissues by reverse transcriptase PCR, We did not find any type of mutation other than polymorphisms in the 48 esophageal carcinomas, though aberration of the p53 gene on the PCR-SSCP gels was observed in 15 of 38 (39%) tumors of the same set. In addition, LOH for p73 was found in only 2 of 25 (8%) tumors. These results suggest that, at least in esophageal carcinomas, allelic loss or mutation of p73 may not be a main genetic event for the tumorigenesis as it is with P53. (C) 1998 Wiley-Liss, Inc.

DOI PubMed CiNii

Mutational analysis of the p73 gene localized at chromosome 1p36.3 in colorectal carcinomas

M Sunahara, S Ichimiya, Y Nimura, N Takada, S Sakiyama, Y Sato, S Todo, W Adachi, J Amano, A Nakagawara

INTERNATIONAL JOURNAL OF ONCOLOGY ( SPANDIDOS PUBL LTD ) 13 ( 2 ) 319 - 323 1998年08月

Genetic alteration of p53, which monitors DNA damage and operates cellular checkpoints, is a major factor in the development of human colorectal carcinoma (CRC). Recently, p73, a novel family member of p53, has been identified and found, like p53, to activate p21(Wafl/Cipl) and to induce apoptosis. The p73 gene was mapped at chromosome 1p36.3 which is a region frequently deleted in CRCs and other cancers including neuroblastoma. To assess whether or not p73 is a tumor suppressor gene of CRC, we performed mutational analysis of p73 in 82 colorectal tumor tissues paired with constitutional DNA. Using a microsatellite marker for p73, the loss of heterozygosity (LOH) study was performed and allelic loss of p73 was found in 17% of the CRCs. RT-PCR single strand conformation polymorphism analysis showed no mutation except three polymorphisms in the p73 coding region. In addition, p73 was expressed at higher levels in the CRC tissues than in the normal mucosa or neuroblastoma tissues, though the transcripts were detectable only by the RT-PCR method. Our results suggest that, in CRCs, p73 may not play a role as a tumor suppressor, at least not in a classic Knudson manner.

骨軟部腫瘍に対するp73遺伝子異常の検索

花岡英二, 井上雅俊, 一宮慎吾, 高田尚幸, 二村好憲, 舘崎慎一郎, 梅田透, 櫛田和義, 守屋秀繁, 中川原章

日本整形外科學會雜誌 = The Journal of the Japanese Orthopaedic Association 72 ( 6 ) S1022 1998年06月

CiNii

Mutation, allelotyping, and transcription analyses of the p73 gene in prostatic carcinoma

H Takahashi, S Ichimiya, Y Nimura, M Watanabe, M Furusato, S Wakui, R Yatani, S Aizawa, A Nakagawara

CANCER RESEARCH ( AMER ASSOC CANCER RESEARCH ) 58 ( 10 ) 2076 - 2077 1998年05月

A novel gene,p73, encoding a protein with significant homology to p53, was recently identified at 1p36, To investigate penetrance of p73 in prostatic carcinogenesis, mutation, allelotyping, and transcription analyses of p73 were performed in prostatic carcinoma. No types of mutation causing amino acid substitutions or frameshifts were found in 106 cases examined. Loss of heterozygosity in the gene was found in 2 of 38 cases (5.3%), Various expression levels of p73 alpha variant were observed in tumor compared with those in normal tissue. These data suggest that the p73 gene is not playing an essential role, but expression of p73 may associate with tumor growth in prostatic carcinogenesis.

Glial cell line-derived neurotrophic factor neurturin-induced differentiation and its enhancement by retinoic acid in primary human neuroblastomas expressing c-Ret, GFR alpha-1, and GFR alpha-2

T Hishiki, Y Nimura, E Isogai, K Kondo, S Ichimiya, Y Nakamura, T Ozaki, S Sakiyama, M Hirose, N Seki, H Takahashi, N Ohnuma, M Tanabe, A Nakagawara

CANCER RESEARCH ( AMER ASSOC CANCER RESEARCH ) 58 ( 10 ) 2158 - 2165 1998年05月

Neuroblastomas often undergo spontaneous differentiation and/or regression in vivo, which is at least partly regulated by the signals through neurotrophins and their receptors, Recently, glial cell line-derived neurotrophic factor (GDNF) and a second family member, neurturin (NTN), have been found to mediate their signals by binding to a heterotetrameric complex of c-Ret tyrosine kinase receptors and glycosylphosphatidylinusitol-linked proteins, GFR alpha-1 (GDNFR-alpha) or GFR alpha-2 (TrnR2/GDNFR-beta/ NTNR-alpha/RETL2). Here, we studied the effect of GDNF and NTN on human neuroblastomas in the short-term primary culture system, as well as the expression of c-Ret, GFR alpha-1, GFR alpha-2, GDNF, and NTN. GDNF (1-100 ng/ml) induced morphological differentiation in 34 of 38 primary neuroblastomas and an accompanying increase in c-Fos induction. These effects were markedly enhanced by treatment with 5 mu M all-bans-retinoic acid. Although GDNF alone induced a rather weak differentiation independent of the disease stages, the enhancement of neurite outgrowth induced by treatment with both GDNF and all-trans-retinoic acid was significantly correlated with younger age (less than 1 year; P = 0.0039), non-stage 4 diseases (P = 0.0023), a single copy of N-myc (P = 0.027), and high levels of TRK-A expression (P = 0.0062). To examine the expression levels of GFR alpha-1, we cloned a short form of the human GFR alpha-1 gene with a 15-bp deletion by screening a human adult substantia nigra cDNA library. Many primary neuroblastomas expressed c-Ret, GFR alpha-1, and GFR alpha-2 as well as their ligands, GDNF and NTN, suggesting the presence of a paracrine or autocrine signaling system within the tumor tissue. The effect of NTN on primary culture cells of neuroblastoma was similar to that of GDNF, These imply that the GDNF(NTN)/c-Ret/GFR alpha-1(GFR alpha-2) signaling may have an important role in regulating the growth, differentiation, and cell death of neuroblastomas.

食道癌における新規癌抑制遺伝子p73の検討

二村好憲, 一宮慎吾, 砂原正男, 穴倉朋胤, 崎山樹, 関直彦, 大平美紀, 藤森実, 安達亙, 天野純, 中川原章

日本外科学会雑誌 ( 一般社団法人日本外科学会 ) 99 ( 0 ) 378 - 378 1998年03月

CiNii

大腸癌におけるp73(p53ホモログ)の遺伝子変異

砂原正男, 一宮慎吾, 宍倉朋胤, 二村好憲, 高田尚幸, 安達亙, 佐藤裕二, 天野純, 藤堂省, 崎山樹, 中川原章

日本外科学会雑誌 ( 一般社団法人日本外科学会 ) 99 ( 0 ) 498 - 498 1998年03月

CiNii

乳癌における新規p53関連遺伝子p73の検討

穴倉朋嵐, 一宮慎吾, 砂原正男, 二村好憲, 宮内充, 山本尚人, 鈴木正人, 中嶋伸之, 崎山樹, 中川原章

日本外科学会雑誌 ( 一般社団法人日本外科学会 ) 99 ( 0 ) 339 - 339 1998年03月

CiNii

Ectopic expression of DAN enhances the retinoic acid-induced neuronal differentiation in human neuroblastoma cell lines

Y Nakamura, T Ozaki, S Ichimiya, A Nakagawara, S Sakiyama

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS ( ACADEMIC PRESS INC ) 243 ( 3 ) 722 - 726 1998年02月

Retinoic acid (RA) plays a major role in neuronal cell differentiation. Neuroblastoma cells differentiate in vitro by extending neurites and forming ganglion-like aggregates in response to Rk In the present study, we have examined a biological role(s) of-DAN in the regulation of RA-mediated cellular differentiation in neuroblastoma cells. RTBM1 and SH-SY5Y cells undergo marked morphological changes associated with a remarkable induction of DAN gene expression when exposed to Rk By transfecting an expression vector harboring a rat DAN cDNA into SH-SY5Y sells, we have obtained two independent transfectants which express a large amount of DAN. The forced expression of DAN gene enhanced the neurite extension in the presence of RA, suggesting that DAN gene product might contain some regulatory role(s) in the RA-induced cellular differentiation in neuroblastoma cells. (C) 1998 Academic Press.

DOI PubMed CiNii

RT1.P, rat class Ib genes related to mouse TL: evidence that CD1 molecules but not authentic TL antigens are expressed by rat thymus

A Matsuura, S Takayama, M Kinebuchi, Y Hashimoto, K Kasai, D Kozutsumi, S Ichimiya, R Honda, T Natori, K Kikuchi

IMMUNOGENETICS ( SPRINGER VERLAG ) 46 ( 4 ) 293 - 306 1997年08月

CD1 and TL were once thought to be genetic homologues because of their thymus-specific expression. We investigated their equivalents in the rat to clarify whether their structure and pattern of expression are conserved in rodents. Two rat class Ib genes, containing 3' sequences very similar to mouse TL, were identified and designated RT1.P. Neither of them, however, can encode ordinary class I molecules due to the accumulation of harmful mutations in the 5' regions that are unique to RT1.P, while the 3' TL-like regions still retain protein-coding capacity. Comparison of the structural organization of three types of TL family genes, which include mouse T3/T18-encoding TL antigens, mouse T1/T16, and rat RT1.P1/P2 pseudogenes, revealed the presence of a clear demarcation between the type-specific and TL-specific sequences at intron 3. This finding suggests that recombination plays an important role in creating the TL family genes in rodents. Characteristic features of TL, such as a low level of polymorphism and linkage to the major histocompatibility complex, were also observed in the rat. On the other hand, rat CD1 molecules were expressed at a high level on the surface of thymocytes. Absence of authentic TL antigens and thymic expression of CD id molecules in the rat suggest the plasticity and conservation of class Ib genes in rodent evolution. Functions of TL may be substituted with CD1 or other class Ib molecules expressed by rat thymus.

DOI PubMed

Localization of rat CD1 transcripts and protein in rat tissues - An analysis of rat CD1 expression by in situ hybridization and immunohistochemistry

K Kasai, A Matsuura, K Kikuchi, Y Hashimoto, S Ichimiya

CLINICAL AND EXPERIMENTAL IMMUNOLOGY ( BLACKWELL SCIENCE LTD ) 109 ( 2 ) 317 - 322 1997年08月

CD1 molecules are cell surface glycoproteins non-covalently associated with Pz-microglobulin. Recently, functional features of the CD1 family such as a target ligand and an antigen-presenting structure for T cells have been reported. In the current study, tissue distribution of rat CD1 was analysed by in situ hybridization (ISH) in conjunction with immunohistochemistry to clarify the precise localization of both transcripts and proteins. CD1 transcripts were detected by ISH in a variety of organs: spleen, thymus, liver, lung, heart, kidney, small intestine and skin. In most organs, CD1 immunoreactivity paralleled the amount of CD1 mRNA expression and was localized in the same regions as its gene transcripts. However, there was a clear difference between the level of rat CD1 transcription and protein expression in the small intestine. CD1 mRNA was detected in the enterocytes of crypts of Lieberkuhn, but not in those of the intestinal villi, while immunoreactivity of CD1 protein was observed in the cells of the intestinal villi but not in those of crypts of Lieberkuhn. This suggests that CD1 gene transcription occurs in the enterocytes of intestinal crypts, and that as the cells of intestinal crypts migrate from the crypts to the intestinal villi, CD1 proteins are synthesized and accumulated in the intestinal villi. Such CD1 expression in the enterocytes appears to be consistent with migration-associated differentiation, and suggests that rat CD1 may take part in mucosal immunity as a first line of defence. In addition, clear cell membrane CD1 immunoreactivity on lymphoid cells raises the possibility that intercellular interaction via rat CD1 and T cell receptors may be involved in both lymphoid cell differentiation and immunoregulation.

Rat CD1 antigen: Structure, expression and function

A Matsuura, Y Hashimoto, M Kinebuchi, K Kasai, S Ichimiya, S Katabami, H Chen, T Shimizu, K Kikuchi

TRANSPLANTATION PROCEEDINGS ( ELSEVIER SCIENCE INC ) 29 ( 3 ) 1705 - 1706 1997年05月

DOI

　前のページ - 次のページ　

<一宮 慎吾>

Misc - 一宮 慎吾

<一宮　慎吾>

Misc - 一宮　慎吾