研究者詳細 - 時野　隆至

論文 - 時野　隆至

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p53類似遺伝子p73,p51の抗腫瘍効果についての検討

佐々木泰史, 森本一郎, 中谷宇一郎, 石田勢津子, 山下利春, 今井浩三, 鬼原史, 田中敏博, 中村祐輔, 時野隆至

日本癌学会総会記事 ( (一社)日本癌学会 ) 59回 55 - 55 2000年09月

Ewing肉腫特異的なEWS-ETS融合転写因子の標的遺伝子

吉田幸一, 佐々木泰史, 梅沢明弘, 秦順一, 鬼原史, 田中敏博, 中村祐輔, 時野隆至

日本癌学会総会記事 ( (一社)日本癌学会 ) 59回 53 - 53 2000年09月

子宮頸部,内膜細胞診,組織診とヒトパピローマウイルス(HPV)型,K-rasとの関係

梶野由里, 山口昭弘, 新家瑠奈, 清野邦義, 日野順子, 沓澤武, 時野隆至, 佐藤昇志, 小野江和則, 菊地浩吉

日本病理学会会誌 ( (一社)日本病理学会 ) 89 ( 1 ) 238 - 238 2000年03月

Apoptotic signaling cascade is regulated by p53 status in X-ray- irradiated cells

D. Kobayashi, T. Tokino, N. Watanabe

Biotherapy 14 ( 5 ) 482 - 484 2000年

Objectives: In the present study, we investigated the effect of the p53 status on the signal transduction pathway of X-ray-induced apoptosis using temperature sensitive p53-transduced rat embryonic fibroblast (REF 112) cells. Materials and Methods: (1) The cytotoxicity and apoptosis were examined by WST-8 reagent, DNA fragmentation assay and Hoechst 33258 staining. (2) The p53 and p21/WAF-1 expression was determined using indirect fluorescein-labeled antibody method and analyzed with Spectrafluor (SLT Labinstruments). (3) Caspase-3 activity was assayed by fluorometric real-time assay using Spectrafluor. Results: (1) There was 50% cell death by 5 Gy of X- ray irradiation in cells at mt p53 status, and this cytotoxicity was abrogated almost completely with specific caspase-3 inhibitor Ac-DMQD-CHO. In addition, caspase-3 activity increased approximately 5 times at 24 h after treatment, and this increased activity was almost completely inhibited by the administration of antioxidant N-acetyl-L-cysteine (NAC). This NAC treatment also abrogated X-ray induced cytotoxicity. However, there was no induction of p53 and p21/WAF-1. (2) In contrast, the cells in wt p53 status were more resistant to X-ray compared to cells in mt p53 status. X-ray induced cytotoxicity was not inhibited by Ac-DMQD-CHO, and caspase-3 activity was not elevated, though there was an apparent induction of p53 and p21/WAF-1. Conclusion: These findings suggest that caspase-3 activation downstream of reactive oxygen species occurs during radiation-induced apoptosis in the cells carrying mutant p53, while p21/WAF-1 induction by p53 has a crucial role at wild p53 status.

Nineteenth International Symposium on Cancer, Sapporo, 7-9 July 1999: Cancer genomics and molecular diagnosis - The Nineteenth International Symposium of Sapporo Cancer Seminar

M. Perucho, T. Tokino, Y. Nakamura

Japanese Journal of Cancer Research 90 ( 11 ) 1273 - 1276 1999年 [査読有り]

PubMed

著しい骨髄の線維化と全身性の骨転移を伴った節外性非Hodgkinリンパ腫

笠原薫, 高橋徹, 岡俊州, 山本元久, 白田智洋, 井戸川雅史, 苗代康可, 林敏昭, 安達正晃, 日野田祐治, 今井浩三

臨床血液 39 ( 12 ) 1180 - 1184 1998年12月

A 68-year-old woman was admitted in March 1997 because of lumbago, fever, vomiting, and general malaise. Laboratory data disclosed anemia and severe hypercalcemia (7.7 mEq/l). Multiple osteolytic lesions were detected in the patient's vertebra, pelvis, and bilateral tibia by x-ray films and 99mTc bone scintigrams. Bone marrow aspiration sample was not obtained due to dry tap. Marked myelofibrosis and proliferation of lymphoid cells were revealed by a bone marrow biopsy specimen. Immunohistochemical analysis showed that cells in the biopsy specimen were positive for L-26 and LCA, but not for UCHL-1. Gastrointestinal endoscopic examination found multiple polypoid lesions in the stomach; biopsy specimens of the lesion tissue disclosed invasion by B lymphoid cells. A diagnosis of diffuse large B cell lymphoma was thus made. THP-COP chemotherapy was performed, but only minimal response was obtained. Lymphoma cells subsequently invaded the brain stem, and the patient eventually died of respiratory failure.

DOI PubMed CiNii

GML遺伝子導入によってもたらされる細胞増殖抑制機構の解析

上田和毅, 三好康雄, 木村康利, 時野隆至, 綿谷正弘, 安富正幸, 中村祐輔

日本癌学会総会記事 ( 日本癌学会 ) 57回 160 - 160 1998年08月 [査読有り]

p53により発現が誘導される新規遺伝子の単離

井阪茂之, 三好康雄, 時野隆至, 東千尋, 村田雄二, 中村祐輔

日本癌学会総会記事 ( (一社)日本癌学会 ) 57回 440 - 440 1998年08月

Cloning and characterization of BAI2 and BAI3, novel genes homologous to brain-specific angiogenesis inhibitor 1 (BAI1)

T. Shiratsuchi, H. Nishimori, H. Ichise, Y. Nakamura, T. Tokino

Cytogenetic and Genome Research 79 ( 1-2 ) 103 - 108 1997年01月 [査読有り]

We have identified two novel human genes homologous to BAH (brain-specific angiogenesis inhibitor 1), an angiogenesis inhibitor that is a candidate for involvement in development of glioblastoma. Like BAH, these two genes, designated BAI2 and BAD, were specifically expressed in brain, and are likely to be expressed in the same type of cells. However, in spite of similar tissue specificity among the three BAI genes, only BAH is transcriptionally regulated by p53. BAD expression was absent in two of nine glioblastoma cell lines examined and was significantly reduced in three of the remaining seven. These data suggest that members of this novel gene family may play important roles in suppression of glioblastoma. BAH, BAI2 and BAI3 were mapped to 8q24, 1p35 and 6q12, respectively. © 1997 S. Karger AG, Basel.

DOI

Cloning, expression and mapping of a novel human zinc-finger gene TCF17 homologous to rodent Kid1

Y. Omori, H. Kyushiki, S. Takeda, M. Suzuki, A. Kawai, T. Fujiwara, E. Takahashi, Y. Nakamura

Cytogenetic and Genome Research 78 ( 3-4 ) 285 - 288 1997年01月

We isolated a novel human zinc-finger gene TCF17 homologous to rat Kid1, a zinc-finger gene of the Kr�ppel type expressed predominantly in kidney. In the rat this gene seems to be a transcription factor expressed in response to renal injury and ischemia. The 2435-bp human cDNA contained an open reading frame encoding 605 amino acids. The deduced amino acid sequence showed 86.0% and 87.2% identity (91.6% and 92.8% similarity) with the rat Kid1 and mouse Tcf17 respectively. In contrast with rat Kid1, human TCF17 was expressed in all human tissues examined, including kidney. This gene was mapped by FISH to chromosome 5q35.3, where cytogenetic and molecular abnormalities have been reported often in renal cell carcinomas. © 1997 S. Karger AG, Basel.

DOI PubMed

Cloning, expression and chromosome mapping of adducin-like 70 (ADDL), a human cDNA highly homologous to human erythrocyte adducin

T. Katagiri, K. Ozaki, T. Fujiwara, F. Shimizu, A. Kawai, S. Okuno, M. Suzuki, Y. Nakamura, E. Takahashi, Y. Hirai

Cytogenetic and Genome Research 74 ( 1-2 ) 90 - 95 1996年01月 [査読有り]

From a human fetal-brain cDNA library we isolated a novel human cDNA, termed human adducin-like 70 (gene symbol ADDL), whose predicted amino acid sequence showed a high degree of homology to adducins. This cDNA clone (ADDL), which contained an open reading frame of 2,022 nucleotides encoding 674 amino acids, revealed 54%, 53%, and 59% identity in predicted amino acid sequence with alpha and beta components of human adducin and rat adducin 63, respectively. Human adducin-like 70 is likely to play an important role in the skeletal organization of the cell membrane. Northern blot analysis indicated ubiquitous expression of this gene in adult human tissues. We localized the gene to chromosome bands 10q24.2→q24.3 by fluorescence in situ hybridization (FISH). © 1996 S. Karger AG, Basel.

DOI PubMed

Isolation, characterization and chromosomal assignment of the human WNT7A gene

S. Ikegawa, Y. Kumano, K. Okui, T. Fujiwara, E. Takahashi, Y. Nakamura

Cytogenetic and Genome Research ( S. Karger AG ) 74 ( 1-2 ) 149 - 152 1996年

DOI

Fifty novel sequence-tagged sites (STSs) on human chromosome 11q13.4→q25 identified from microclones generated by microdissection

H. Soejima, K. Yoshiura, T. Tamura, T. Tokino, Y. Nakamura, N. Niikawa, Y. Jinno

Cytogenetic and Genome Research 70 ( 1-2 ) 108 - 111 1995年 [査読有り]

Fifty sequence-tagged sites (STSs) from human chromosome region, 11q13.4→q25 were identified in micro-dissection-generated microclones. From a total of 124 single-copy microclones obtained from regions 11q14→q22 and 11q23→q25, 59 were sequenced, and a PCR primer pair was designed for each of them. Fifty of the 59 clones were mapped to regions ranging from 11q1 3.4 to 1 1q25 by means of PCR on a somatic hybrid cell panel with various deletions of the long arm of human chromosome 11. These STSs will contribute to the construction of physical cosmid/YAC maps representing the chromosome regions. They are also useful for analysis of chromosome aberrations, such as translocations, inversions or marker chromosomes. © 1995 S. Karger AG, Basel.

DOI PubMed

Identification and characterization of a cdna, which is highly homologous to the ribonucleoprotein gene, from a locus (D10s102) closely linked to men2 (multiple endocrine neoplasia type 2)

S. Takiguchi, T. Tokino, T. Imai, A. Tanigami, K. Koyama, Y. Nakamura

Cytogenetic and Genome Research 64 ( 2 ) 128 - 130 1993年 [査読有り]

We previously reported a nearly 1-Mb contig of cosmid and YAC clones at D10S102, a locus that is tightly linked to the gene responsible for multiple endocrine neoplasia type 2 (MEN2A). Subclones of 159 genomic EcoRI fragments in the contig were tested on “zoo blot” to detect DNA sequences conserved in various species. Nine fragments found to contain conserved sequences were used as probes for screen ing cDNA libraries. One of these probes, y300-pL50, recognized a cDNA from a human fetal brain library. The cDNA encoded a protein consisting of 270 amino acids, whose predicted sequence has a high degree of homology to heterogeneous nuclear ribonuclear protein. This expressed sequence may be a candidate for the gene responsible for MEN2A. © 1993 S. Karger AG, Basel.

DOI PubMed

A 14-MB PHYSICAL MAP OF THE REGION AT CHROMOSOME-11Q13 HARBORING THE MEN1 LOCUS AND THE TUMOR AMPLICON REGION

A TANIGAMI, T TOKINO, K TAKITA, S TAKIGUCHI, Y NAKAMURA

GENOMICS ( ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS ) 13 ( 1 ) 16 - 20 1992年05月 [査読有り]

Different type of hepatitis B virus (HBV) DNA integrants that may reflect the integration process

Kousaku Okubo, Takaaki Nakamura, Takashi Tokino, Kenichi Matsubara

Gastroenterologia Japonica ( Springer-Verlag ) 25 ( 2 ) 23 - 30 1990年09月 [査読有り]

Through analyses of HBV DNA integratns in human cellular DNA, we identified three different integrant types, each of which may reflect the process of primary integrant formation by the viral DNA. The first type, which we call "simple type" consists of integrants found in some hepatocellular carcinomas (HCC's). The structure of the viral genome is simple, and part of it is deleted. The viral cohesive end sequence appears at one of the viral-cellular DNA junctions, and integration has elicited a microdeletion in the target cellular DNA sequence. This structure suggests viral DNA replication intermediates as substrates for integration. Judging from its frequency in HCC, this type may represent the most preferred one, if not all, among the primary integration products. The second type, which we call "complex type" is essentially the same as the first type, except tht the viral genome structure is complex. We considered the possibility that they may have been produced via the same process, using preformed complex viral genomes such as "novel form DNA's" (Rogler and Summers, 1982) as substrates. In cultured fetal hepatocytes, integration of HBV DNA can occur only a few days after infection. Among such integrants, we found a third type integrant, having a simple viral genome, but having a larger cellular DNA deletion. We propose that different forms of viral DNA may be used a ssubstrates in the integration process, and the process is characterized by its eliciting of deletions of different size in the target cellular DNA. The most preferred substrate may be the one producing the simple type integrants, and the most frequently occurring deletion in the target DNA may be the microdeletion. The structure of one of the early integrants is different from any of the above, and its formation seems to have a deleterious effect on the chromosome in which the integration occurs, and hence to the host cell. © 1990 The Japanese Society of Gastroenlerology.

DOI PubMed

Regional localization of the LCA oncogene to human chromosome region 2q14→q21

T. Tokino, H. Satoh, M. C. Yoshida, T. Ochiya, K. Matsubara

Cytogenetic and Genome Research 48 ( 1 ) 63 - 64 1988年 [査読有り]

DOI PubMed

CARRIER DETECTION IN JAPANESE HEMOPHILIA A FAMILIES USING FACTOR-VIII GENE PROBE (F8A) AND THE GENE-LINKED ST 14-1 PROBE

M NISHINO, T NISHIMURA, H NAKA, S MIKAMI, T TOKINO, T MUROTSU

JAPANESE JOURNAL OF HUMAN GENETICS ( TOKYO MEDICAL DENTAL UNIV ) 32 ( 3 ) 237 - 245 1987年09月 [査読有り]

Carrier detection in Japanese haemophilia a families using factor VIII gene probe (F8A) and the gene-linked ST 14-1 probe

Masato Nishino, Takuya Nishimura, Hiroyuki Naka, Sadaaki Mikami, Takashi Tokino, Tomoaki Murotsu

The Japanese Journal of Human Genetics ( Springer-Verlag ) 32 ( 3 ) 237 - 245 1987年09月 [査読有り]

Carriers of haemophilia A were detected in 20 Japanese families with using the factor VIII gene probe (F8A) and the gene-linked ST 14-1 probe. Polymorphism by the use of the BclI and F8A probe detected the smaller allele (0.9 kb) in 86% and the larger allele (1.2 kb) in 14% of the 65 normal X chromosomes. The frequency of BclI polymorphism was 30% in 30 normal fameles. In six out of 20 haemophilia A families, the haemophilia gene was identified by BclI allele polymorphism. The use of TaqI and the ST 14-1 probe detected 11 carriers in 20 haemophilia A families. In 14 families (70%), either the BclI polymorphism in the factor VIII locus or TaqI polymorphisms in the ST 14 locus was useful for carrier detection. © 1987 The Japan Society of Human Genetics.

DOI PubMed

Replication of mini-F plasmid in vitro promoted by purified E protein

Kanae Muraiso, Takashi Tokino, Tomoaki Murotsu, Kenichi Matsubara

MGG Molecular & General Genetics ( Springer-Verlag ) 206 ( 3 ) 519 - 521 1987年03月 [査読有り]

An in vitro system for replication of mini-F plasmid DNA was constructed. This system consists of an ammonium sulfate fraction II (Fuller et al. 1981) from Escherichia coli extract, exogeneously added purified E protein encoded by mini-F plasmid, and mini-F DNA in a closed circular form. Experiments with this system showed that the 217 bp DNA region which contains the A+T rich cluster and the four 19 bp direct repeats responsible for incB incompatibility is essential for mini-F DNA replication. © 1987 Springer-Verlag.

DOI PubMed

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