研究者詳細 - 時野　隆至

論文 - 時野　隆至

分割表示 360 件中 321 - 340 件目／全件表示 >>

Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer.

Hiromu Suzuki, D Neil Watkins, Kam-Wing Jair, Kornel E Schuebel, Sanford D Markowitz, Wei Dong Chen, Theresa P Pretlow, Bin Yang, Yoshimitsu Akiyama, Manon Van Engeland, Minoru Toyota, Takashi Tokino, Yuji Hinoda, Kohzoh Imai, James G Herman, Stephen B Baylin

Nature genetics 36 ( 4 ) 417 - 22 2004年04月 [査読有り] [国際誌]

Aberrant WNT pathway signaling is an early progression event in 90% of colorectal cancers. It occurs through mutations mainly of APC and less often of CTNNB1 (encoding beta-catenin) or AXIN2 (encoding axin-2, also known as conductin). These mutations allow ligand-independent WNT signaling that culminates in abnormal accumulation of free beta-catenin in the nucleus. We previously identified frequent promoter hypermethylation and gene silencing of the genes encoding secreted frizzled-related proteins (SFRPs) in colorectal cancer. SFRPs possess a domain similar to one in the WNT-receptor frizzled proteins and can inhibit WNT receptor binding to downregulate pathway signaling during development. Here we show that restoration of SFRP function in colorectal cancer cells attenuates WNT signaling even in the presence of downstream mutations. We also show that the epigenetic loss of SFRP function occurs early in colorectal cancer progression and may thus provide constitutive WNT signaling that is required to complement downstream mutations in the evolution of colorectal cancer.

DOI PubMed CiNii

Epigenetic inactivation of TMS1/ASC in ovarian cancer.

Katsuhiko Terasawa, Satoru Sagae, Minoru Toyota, Kuniko Tsukada, Kazuhiro Ogi, Ayumi Satoh, Hiroaki Mita, Kohzoh Imai, Takashi Tokino, Ryuichi Kudo

Clinical cancer research : an official journal of the American Association for Cancer Research 10 ( 6 ) 2000 - 6 2004年03月 [査読有り] [国際誌]

PURPOSE: The purpose of this work was to explore the role of epigenetic inactivation of apoptotic pathways in ovarian cancer by examining the DNA methylation and expression status of four proapoptotic genes in primary ovarian cancers and cancer cell lines and to correlate those findings with the clinicopathological features of ovarian cancer patients. EXPERIMENTAL DESIGN: Genomic DNA was isolated from 15 ovarian cancer cell lines, 80 primary ovarian cancer specimens, and 4 normal ovary specimens using phenol-chloroform extraction. The methylation status of the DNA was evaluated using combined bisulfite restriction analysis, gene expression was evaluated using reverse transcription-PCR, and histone acetylation was evaluated using chromatin immunoprecipitation. RESULTS: Of the four proapoptotic genes studied, expression of TMS1/ASC was absent in six ovarian cancer cell lines. Dense methylation of the 5' region of TMS1/ASC was detected in cells not expressing TMS1/ASC. Treating methylated cells with 5-aza-deoxycytidine restored gene expression, confirming the role of methylation in silencing the gene. Chromatin immunoprecipitation revealed histone to be deacetylated in cells not expressing TMS1/ASC, indicating that histone deacetylation is also involved in silencing TMS1/ASC. Aberrant methylation of TMS1/ASC was detected in 15 of 80 ovarian cancer tissues (19%) but in none of the normal ovary specimens. Aberrant methylation of TMS1/ASC was observed significantly more often in clear cell-type ovarian cancers than in other tumor types (P < 0.0001). CONCLUSIONS: Methylation-mediated silencing of TMS1/ASC confers a survival advantage to tumor cells by enabling them to escape apoptosis. The role for aberrant methylation in human ovarian tumorigenesis may be particularly important for ovarian cancers with the clear cell phenotype.

DOI PubMed

Regulation of MHC class II expression in glioma cells by class II transactivator (CIITA).

Yukio Takamura, Hideyuki Ikeda, Takayuki Kanaseki, Minoru Toyota, Takashi Tokino, Kohzoh Imai, Kiyohiro Houkin, Noriyuki Sato

Glia 45 ( 4 ) 392 - 405 2004年03月 [査読有り] [国際誌]

We first classified 12 malignant glioma cell lines into three different groups (types 1-3) with respect to major histocompatibility complex (MHC) class II expression and analyzed each group based on the different expression status of the class II transactivator (CIITA) gene. Glioma type 1 (2 of 12) showed constitutive expression of all class II molecules that might be mediated by activation of B cell-specific CIITA promoter III. Glioma type 2 represented the major phenotype (66.7 %) of malignant glioma cell lines, and MHC class II expression was induced by interferon-gamma (IFN-gamma) in this phenotype. Analysis of glioma tissue samples revealed that CIITA promoter IV was detected in 9 of 11 patients (81.8%); however, promoter III was only in two (18.2%). Moreover, cultured glioma cells obtained from a fresh tumor sample upregulated expression of CIITA and class II molecules in the presence of IFN-gamma, strongly suggesting that glioma type 2 might be predominant in glioma tissues. Glioma type 3 (2 of 12) showed CIITA transcripts but loss of MHC class II expression even in the presence of IFN-gamma. In addition, we determined that the constitutive MHC class II expression in the glioma cell lines (type 1) was the result of transcriptional activation of the CIITA gene. This phenomenon was mediated by global histone acetylation over 6 kb upstream from the transcriptional start site of CIITA promoter III. Moreover, stable transfection of CIITA promoter IV as well as promoter III into MHC class II inducible cell lines restored the constitutive expression of all class II molecules. These studies lay the foundation to understand the molecular basis for the expression of class II molecules in gliomas.

DOI PubMed

Inactivation of class II transactivator by DNA methylation and histone deacetylation associated with absence of HLA-DR induction by interferon-gamma in haematopoietic tumour cells

Y Morimoto, M Toyota, A Satoh, M Murai, H Mita, H Suzuki, Y Takamura, H Ikeda, T Ishida, N Sato, T Tokino, K Imai

BRITISH JOURNAL OF CANCER ( NATURE PUBLISHING GROUP ) 90 ( 4 ) 844 - 852 2004年02月

By presenting immunogenic peptides at the cell surface, major histocompatibility complex (MHC) class II molecules play a key role in the control of adaptive immune responses. Whether expressed constitutively or induced by interferon-gamma, expression of MHC class II molecules is regulated via coactivator class II transactivator (CIITA); moreover, suppression of their expression is one mechanism by which cancer cells escape host immunity. In this study, we surveyed the relationship between the expression of one MHC class II antigen, HLA-DR, and its coactivators in a group of haematopoietic cell lines, and explored the role of the aberrant DNA methylation in silencing HLA-DR expression. Among 26 cell lines studied, HLA-DR expression was lost from eight T-cell and two myeloid leukaemia cell lines, and this loss was closely associated with suppression of CIITA-PIV expression. Notably, nine of the 10 cell lines that lost CIITA-PIV expression showed methylation of the gene's 5' CpG island. Thus, DNA methylation is believed to inhibit the expression of MHC class II molecules in haematopoietic tumour cells by silencing its coactivator, CIITA-PIV. Furthermore, methylation of CIITA-PIV was detected in seven of 32 primary acute myeloid leukaemia specimens, indicating that epigenetic alteration is not a cell line-specific phenomenon. Collectively, these data suggest that, by suppressing expression of MHC class II molecules, epigenetic inactivation of CIITA provides a survival advantage to a subset of haematopoietic tumours.

DOI

Aberrant methylation and histone deacetylation associated with silencing of SLC5A8 in gastric cancer

M Ueno, M Toyota, K Akino, H Suzuki, M Kusano, A Satoh, H Mita, Y Sasaki, M Nojima, K Yanagihara, Y Hinoda, T Tokino, K Imai

TUMOR BIOLOGY ( KARGER ) 25 ( 3 ) 134 - 140 2004年

Aberrant methylation of a sodium co-transporter, solute carrier family 5 member 8 gene (SLC5A8), has been detected in a subset of colorectal cancers, suggesting SLC5A8 may also serve as a tumor suppressor. To further investigate the role of epigenetic inactivation of SLC5A8 expression in gastric cancer, we determined the methylation status of the SLC5A8 5' CpG island (CGI) in a panel of gastric cancer cell lines and primary gastric cancers. We detected methylation of the 5' CGI in ten of twelve gastric cancer cell lines, and five of those showed dense methylation, which correlated with the absence of SLC5A8 transcription. Aberrant methylation of SLC5A8 was also detected in 23 of 71 (30%) primary gastric cancers, indicating that epigenetic inactivation of SLC5A8 is not a cell-line-specific phenomenon. SLC5A8 expression was restored in methylated cell lines by treatment with 5-aza-2'-deoxycytidine, a methyltransferase inhibitor. In addition, chromatin immunoprecipitation assays showed that acetylation of histone H3 in the 5' region of the gene correlated directly with SLC5A8 expression and inversely with DNA methylation. It thus appears that aberrant methylation of its 5' CGI and histone deacetylation play key roles in silencing SLC5A8 expression in gastric cancers. Copyright (C) 2004 S. Karger AG, Basel.

DOI

Epigenetic inactivation of CHFR and sensitivity to microtubule inhibitors in gastric cancer.

Ayumi Satoh, Minoru Toyota, Fumio Itoh, Yasushi Sasaki, Hiromu Suzuki, Kazuhiro Ogi, Takefumi Kikuchi, Hiroaki Mita, Toshiharu Yamashita, Takashi Kojima, Masanobu Kusano, Masahiro Fujita, Masao Hosokawa, Takao Endo, Takashi Tokino, Kohzoh Imai

Cancer research 63 ( 24 ) 8606 - 13 2003年12月 [査読有り] [国際誌]

Mitotic checkpoints prevent errors in chromosome segregation that can lead to neoplasia. Therefore, it is notable that gastric cancers often show impaired checkpoint function. In the present study, we examined the functional consequences of epigenetic inactivation of the mitotic checkpoint gene CHFR in gastric cancers. CHFR expression was silenced by DNA methylation of the 5' region of the gene in 20% of the gastric cancer cell lines tested and in 39% of primary gastric cancers; expression could be restored by treatment with 5-aza-2'-deoxycytidine, a methyltransferase inhibitor. In addition, histones H3 and H4 were found to be deacetylated in cell lines showing aberrant methylation, indicating a role for histone deacetylation in the methylation-dependent gene silencing. Cells not expressing CHFR showed impaired checkpoint function, which led to nuclear localization of cyclin B1 after treatment with docetaxel or paclitaxel, two microtubule inhibitors. Apparently, the absence of CHFR is associated with sensitivity of cells to mitotic stress caused by microtubule inhibition, and restoration of CHFR expression by 5-aza-2'-deoxycytidine or adenoviral gene transfer restored the checkpoint. By affecting mitotic checkpoint function, CHFR inactivation likely plays a key role in tumorigenesis in gastric cancer. Moreover, the aberrant methylation of CHFR appears to be a good molecular marker with which to predict the sensitivity of gastric cancers to microtubule inhibitors.

PubMed

Identification of HRK as a target of epigenetic inactivation in colorectal and gastric cancer.

Toshiro Obata, Minoru Toyota, Ayumi Satoh, Yasushi Sasaki, Kazuhiro Ogi, Kimishige Akino, Hiromu Suzuki, Masafumi Murai, Takefumi Kikuchi, Hiroaki Mita, Fumio Itoh, Jean-Pierre J Issa, Takashi Tokino, Kohzoh Imai

Clinical cancer research : an official journal of the American Association for Cancer Research 9 ( 17 ) 6410 - 8 2003年12月 [査読有り] [国際誌]

PURPOSE: Aberrant methylation of CpG islands can be a good molecular marker for identifying genes inactivated in cancer. We found the proapoptotic gene HRK to be a target for hypermethylation in human cancers and examined the role of such methylation in silencing the gene's expression. EXPERIMENTAL DESIGN: Methylation of HRK was evaluated by bisulfite-PCR and bisulfite sequencing in a group of colorectal and gastric cancer cell lines and primary cancers. Gene expression and histone acetylation were examined by reverse transcription-PCR and chromatin immunoprecipitation analyses, respectively. Apoptosis of cancer cells after treatment with a DNA methyltransferase inhibitor and/or histone deacetylase inhibitor was examined with fluorescence-activated cell-sorting analysis. RESULTS: The region around the HRK transcription start site was methylated in 36% of colorectal and 32% of gastric cancer cell lines and was closely associated with loss of expression in those cell types. HRK expression was restored by treatment with a methyltransferase inhibitor, 5-aza-deoxycytidine, and enhanced further by addition of histone deacetylase inhibitor trichostatin A or depsipeptide. Such restoration of HRK expression was well correlated with induction of apoptosis and enhancement of Adriamycin-induced apoptosis. Expression of other proapoptotic genes, including BAX, BAD, BID, and PUMA, was unaffected by treatment with 5-aza-deoxycytidine. Aberrant methylation of HRK was also frequently detected in primary colorectal cancers that showed methylation of multiple genes, including p16INK4A and hMLH1, and was associated with wild-type p53. CONCLUSION: HRK methylation can be a useful molecular target for cancer therapy in a subset of colorectal and gastric cancers.

PubMed

Identification of the interleukin 4 receptor alpha gene as a direct target for p73.

Yasushi Sasaki, Hiroaki Mita, Minoru Toyota, Setsuko Ishida, Ichiro Morimoto, Toshiharu Yamashita, Toshihiro Tanaka, Kohzoh Imai, Yusuke Nakamura, Takashi Tokino

Cancer research 63 ( 23 ) 8145 - 52 2003年12月 [査読有り] [国際誌]

p73 has a high degree of structural homology to p53 and can activate transcription of p53-responsive genes. However, analysis of p73-deficient mice revealed a marked divergence in the physiological activities of p53 family genes and distinguishes p73 from p53. Mice deficient for p73 exhibit profound defects, including hippocampal dysgenesis, chronic infection, and inflammation, as well as abnormalities in pheromone sensory pathways. p73 plays important roles in neurogenesis, sensory pathways, and homeostatic regulation. Here, we found that the interleukin 4 receptor alpha (IL-4Ralpha) gene is up-regulated by p73 but not significantly by p53 in several human cancer cell lines. IL-4Ralphatranscription is also activated in response to cisplatin, a DNA-damaging agent known to induce p73. By using small interference RNA designed to target p73, we demonstrated that silencing endogenous p73 abrogates the induction of the IL-4Ralpha gene after cisplatin treatment. Furthermore, we identified a p73-binding site in the first intron of the IL-4Ralpha gene that can directly interact with the p73 protein in vivo. This p73-binding site consists of eight copies of a 10-bp consensus p53-binding motif and is a functional response element that is relatively specific for p73 among the p53 family. p73beta promoted localized nucleosomal acetylation through recruitment of coactivator p300, indicating that p73 regulates transcription of IL-4Ralpha through the unique p73-binding site. We also found that p73beta-transfected tumor cells are sensitive to IL-4-mediated apoptosis. Our data suggest that IL-4Ralpha could mediate, in part, certain immune responses and p73-dependent cell death.

PubMed

口腔扁平上皮癌におけるM期チェックポイント遺伝子の発現異常とmicrotubule inhibitor感受性

荻和弘, 豊田実, 田中信幸, 野口誠, 佐藤亜由美, 佐々木泰史, 見田裕章, 鈴木拓, 今井浩三, 時野隆至

日本癌学会総会記事 ( (一社)日本癌学会 ) 62回 222 - 222 2003年08月

MCA-RDA法を用いた消化器癌における新規メチル化標的遺伝子の同定

秋野公臣, 豊田実, 荻和弘, 小畑俊郎, 石井卓, 佐藤亜由美, 村井政史, 丸山玲緒, 見田裕章, 佐々木泰史, 遠藤高夫, 今井浩三, 時野隆至

日本癌学会総会記事 ( (一社)日本癌学会 ) 62回 286 - 286 2003年08月

Epigenetic inactivation of CHFR in human tumors.

Minoru Toyota, Yasushi Sasaki, Ayumi Satoh, Kazuhiro Ogi, Takefumi Kikuchi, Hiromu Suzuki, Hiroaki Mita, Nobuyuki Tanaka, Fumio Itoh, Jean-Pierre J Issa, Kam-Wing Jair, Kornel E Schuebel, Kohzoh Imai, Takashi Tokino

Proceedings of the National Academy of Sciences of the United States of America 100 ( 13 ) 7818 - 23 2003年06月 [査読有り] [国際誌]

Cell-cycle checkpoints controlling the orderly progression through mitosis are frequently disrupted in human cancers. One such checkpoint, entry into metaphase, is regulated by the CHFR gene encoding a protein possessing forkhead-associated and RING finger domains as well as ubiquitin-ligase activity. Although defects in this checkpoint have been described, the molecular basis and prevalence of CHFR inactivation in human tumors are still not fully understood. To address this question, we analyzed the pattern of CHFR expression in a number of human cancer cell lines and primary tumors. We found CpG methylation-dependent silencing of CHFR expression in 45% of cancer cell lines, 40% of primary colorectal cancers, 53% of colorectal adenomas, and 30% of primary head and neck cancers. Expression of CHFR was precisely correlated with both CpG methylation and deacetylation of histones H3 and H4 in the CpG-rich regulatory region. Moreover, CpG methylation and thus silencing of CHFR depended on the activities of two DNA methyltransferases, DNMT1 and DNMT3b, as their genetic inactivation restored CHFR expression. Finally, cells with CHFR methylation had an intrinsically high mitotic index when treated with microtubule inhibitor. This means that cells in which CHFR was epigenetically inactivated constitute loss-of-function alleles for mitotic checkpoint control. Taken together, these findings shed light on a pathway by which mitotic checkpoint is bypassed in cancer cells and suggest that inactivation of checkpoint genes is much more widespread than previously suspected.

DOI PubMed CiNii

deltaNp63alpha functions as both a positive and a negative transcriptional regulator and blocks in vitro differentiation of murine keratinocytes.

King KE, Ponnamperuma RM, Yamashita T, Tokino T, Lee LA, Young MF, Weinberg WC

Oncogene 22 ( 23 ) 3635 - 44 2003年06月 [査読有り] [国際誌]

deltaNp63 is overexpressed in squamous carcinomas where it is associated with proliferation and is believed to enhance cell growth by blocking p53-mediated transactivation. In normal epithelium, deltaNp63alpha protein expression is abundant in basal cells and decreases with differentiation. To explore the biological consequences of deltaNp63alpha overexpression in relation to squamous carcinogenesis, we evaluated its effect on normal squamous differentiation and p53 transactivation function in keratinocytes. Forced overexpression of deltaNp63alpha in primary murine keratinocytes in vitro inhibits morphological differentiation induced by elevated extracellular [Ca(2+)], abrogates Ca(2)(+)-induced growth arrest, and blocks expression of maturation-specific proteins keratin 10 and filaggrin. This suggests that deltaNp63 overexpression in squamous carcinomas may serve to maintain the basal cell phenotype and promote cell survival. deltaNp63alpha blocks transactivation of p53 responsive reporter constructs mediated by endogenous or exogenous p53 at 17 h postinfection, as expected. However, at 41 h, when p53-mediated transactivation is diminished, deltaNp63alpha enhances transactivation of these reporter constructs by 2.2-12-fold over control. Maximal deltaNp63alpha-induced transactivation requires intact p53 responsive elements, but is independent of cellular p53 status. This positive transcriptional function of deltaNp63alpha appears to be cell-type specific, as it is not observed in primary dermal fibroblasts or Saos-2 cells. These findings support deltaNp63alpha as a master regulator of keratinocyte differentiation, and suggest a novel function of this protein in the maintenance of epithelial homeostasis.

DOI PubMed

ヒト腫瘍におけるM期チェックポイント遺伝子CHFRの異常メチル化と発現抑制

佐藤亜由美, 豊田実, 佐々木泰史, 荻和弘, 小畑俊郎, 菊地剛, 鈴木拓, 伊東文生, 時野隆至, 今井浩三

日本癌学会総会記事 ( (一社)日本癌学会 ) 61回 88 - 88 2002年10月

紫外線(UVB)によって転写誘導又は抑制されるヒトメラノサイト遺伝子の解析

金海英, 山下利春, 佐々木泰史, 時野隆至, 神保孝一

日本研究皮膚科学会年次学術大会・総会プログラム ( (一社)日本研究皮膚科学会 ) 27回 189 - 189 2002年08月

p53ファミリー遺伝子の機能解析ー遺伝子治療をめざしてー

佐々木泰史, 時野隆至

札幌医学雑誌 ( 札幌医科大学 ) 71 ( 1〜2 ) 1 - 6 2002年04月 [査読有り]

p53 gene therapy is being tested clinically for the treatment of human cancer, however some cancer models (in vivo and in vitro) are resistant to p53. To explore the potential use of two p53 homologues, p73 and p51/p63, in cancer gene therapy, we introduced p53, p73 and p51/p63 into colorectal cancer cell lines via adenoviral vectors, and compared their effects on cell growth. Among ten cell lines tested, six cell lines displayed a similar response following transduction of p53, p73 beta or p51A/p63 gamma, two lines underwent cell-cycle arrest, three lines exhibited apoptosis and one line showed no-effect following transduction. The effect on cell-cycle progression was variable in the other four cell lines. Interestingly, three cell lines were resistant to p53-mediated apoptosis, including two lines having endogenous wildtype p53 alleles, but underwent apoptosis after transduction of p73 beta or p51A/p63 gamma. Similar to p53, transduction of p51A/p63 gamma induced extensive apoptosis when combined with adriamycin or X-radiation in SW480 cells, which are normally resistant to apoptosis. Transduction of p73 beta and p51A/p63 gamma also reduced the tumorigenicity of two colorectal cancer cells in vivo. These results suggest that adenovirus-mediated p73 beta and p51A/p63 gamma transfer are potential novel approaches for the treatment of human cancers, particularly for tumors that are resistant to p53 gene therapy.

DOI CiNii

Methylated CpG Island Amplification of Representational Difference Analysis for Oral Cancer <Review>

Ogi Kazuhiro, Toyota Minoru, Kohama Geniku, Tokino Takashi

Tumor research : experimental and clinical ( 札幌医科大学 ) 37 9 - 15 2002年

CpG islands are G+C-rich regions approximately 1 kb long that are free of methylation and contain the promoters of many mammalian genes. It has been demonstrated that aberrant methylation of CpG islands is associated with gene silencing of tumor suppressor genes. To examine DNA methylation changes in oral squamous cell carcinoma (OSCC), we have applied a novel genome screening technique, methylated CpG island amplification coupled with representational difference analysis. Using DNA from an OSCC cell line as tester and DNA from normal tongue tissue as driver, DNA sequences aberrantly methylated in OSCC can be obtained. We therefore propose that MCA is a useful technique to study methylation and to isolate CpG islands differentially methylated in cancer.

DOI CiNii

EWS-ETS family融合遺伝子の標的遺伝子の発現解析

渡邊吾一, 西森博幸, 入船秀仁, 佐々木泰史, 前仏均, 田中敏博, 吉田幸一, 石井清一, 中村祐輔, 時野隆至

日本癌学会総会記事 ( (一社)日本癌学会 ) 60回 334 - 334 2001年09月

Dried Feces Spots as an Alternative DNA Source: Detection of K-ras Mutations in Colorectal Cancer Screening

Yamaguchi Akihiro, Hashimoto Naoko, Tsutae Wataru, Seino Kuniyoshi, Osanai Hiroyuki, Yamamoto Naoya, Tokino Takashi, Sato Noriyuki, Kikuchi Kokichi

Tumor research : experimental and clinical ( 札幌医科大学 ) 36 7 - 13 2001年

Detection of genetic alterations in exfoliated intestinal cells into feces is expected to be a novel approach to colorectal cancer screening. We aimed here to detect cancer-related gene mutations in routine fecal specimen; dried feces spots (DFS) on a filter paper especially designated for an automated fecal occult blood (FOB) test. DNA was simply extracted from a 3 mm disc of DFS (including around 10 mg feces) with a boiling procedure followed by a cationic surfactant extraction. K-ras common mutations, as the typical cancer-related gene alterations, were detected with a nested allele specific PCR with microfluorometry (ASP/MFL). Adequate DNA was recovered from 363/451 (80.5%) DFS specimens tested. The K-ras mutations were detected in 2/24 (8.3%) from patients with colorectal cancer and 13/315 (4.1%) from screening participants with positive FOB. No mutations were detected in 24 DFS specimens with negative FOB. The results of K-ras mutation frequency were not encouraging to achieve practically a specific dreliable method for colorectal cancer screening. However this report, identifying for the first time a cancer related gene alteration in feces using identical samples with routine FOB test, will be a step to realize a molecular genetic testing for the cancer screening.

DOI CiNii

ヒト大腸癌由来細胞株におけるp53類似遺伝子p73,p51によるアポトーシス誘導と抗癌剤との併用効果

石田勢津子, 佐々木泰史, 森本一郎, 中谷宇一郎, 山下利春, 今井浩三, 時野隆至

日本癌学会総会記事 ( (一社)日本癌学会 ) 59回 324 - 324 2000年09月

頭頸部癌におけるβ-catenin遺伝子の蛋白発現とmutation,増殖因子受容体の発現

小田島哲世, 佐々木泰史, 山口晃, 田中信幸, 池田健, 佐藤昌明, 時野隆至

日本癌学会総会記事 ( (一社)日本癌学会 ) 59回 162 - 162 2000年09月

　前のページ - 次のページ　

<時野 隆至>

論文 - 時野 隆至

<時野　隆至>

論文 - 時野　隆至