Details of a Researcher - IYAMA Satoshi

Papers - IYAMA Satoshi

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Induction of heat shock protein 47 synthesis by TGF-beta and IL-1 beta via enhancement of the heat shock element binding activity of heat shock transcription factor 1

H Sasaki, T Sato, N Yamauchi, T Okamoto, D Kobayashi, S Iyama, J Kato, T Matsunaga, R Takimoto, T Takayama, K Kogawa, N Watanabe, Y Niitsu

JOURNAL OF IMMUNOLOGY ( AMER ASSOC IMMUNOLOGISTS ) 168 ( 10 ) 5178 - 5183 2002.05 [Refereed]

With most immunological reactions, tissue fibrosis, collagen overproduction caused by immune cytokines, is inevitably associated. Among the various immune cytokines, heat shock protein 47 (HSP47) is a procollagen-specific molecular chaperon and is essential for secretion of procollagen from cells. Induction of HSP47 by TGF-beta has been previously reported in rat skeletal myoblasts and mouse osteoblasts, but not in human diploid fibroblasts. As for IL-1beta, its effect on HSP47 has not been elucidated. In the present study, using human embryonic lung fibroblast cells, we first disclosed that both TGF-beta and IL-1beta induced HSP47 synthesis. We then revealed that the binding of the heat shock element (HSE) by heat shock transcription factor 1 (HSF1) was enhanced by both cytokines. We further demonstrated that trimer formation of HSF1, which is essential for its binding to HSE, was induced by these cytokines. The enhancement of HSP47 synthesis and their trimer formation of HSF1 were augmented by using a combination of both cytokines. Collectively, TGF-beta and IL-1beta were found to induce trimer formation of HSF1 which in turn bound to HSE of HSP47, resulting in the enhancement of HSP47 expression. Thus, HSP47 could well be a good candidate for molecular targeting in controlling tissue fibrosis, given that both principal fibrinogenetic cytokines (TGF-beta, IL-1beta) are commonly involved in its induction through HSF1 trimerization.

PubMed

E1B-55K-deleted adenovirus expressing E1A-13S by AFP-enhancer/promoter is capable of highly specific replication in AFP-producing hepatocellular carcinoma and eradication of established tumor

M Takahashi, T Sato, T Sagawa, Y Lu, Y Sato, S Iyama, Y Yamada, J Fukaura, S Takahashi, K Miyanishi, T Yamashita, K Sasaki, K Kogawa, H Hamada, J Kato, Y Niitsu

MOLECULAR THERAPY ( ACADEMIC PRESS INC ELSEVIER SCIENCE ) 5 ( 5 ) 627 - 634 2002.05 [Refereed]

Here, we constructed a recombinant replication-competent adenovirus (rRCAd; AdAFPep/Rep) that expresses both E1A-13S driven by the alpha-fetoprotein (AFP) enhancer/promoter (AFPep) lacking any silencers in the 5'-flanking region of the AFP gene, and 55K-deleted E1B driven by the cytomegalovirus (CMV) promoter. We then examined the feasibility of gene therapy utilizing this virus for AFP-producing hepatocellular carcinoma (HCC). AdAFPep/Rep lysed all the AFP-producing HCC cell lines (HuH7, HepG2, PLC/PRF/5 (P5)) examined at a multiplicity of infection (MOI) as low as 0.1 and did not lyse primary human hepatocytes (Hc) at a MOI as high as 100, indicating that the rRCAd virus can lyse AFP-producing HCC cells with a higher specificity and potency than previously reported. Furthermore, this virus was capable of complete eradication of a preestablished HuH7-cell tumor by a single intratumoral injection of 10(8) plaque-forming units (pfu) of AdAFPep/Rep. Thus, AdAFPep/Rep may be applicable for clinical use.

DOI PubMed

Treatment of murine collagen-induced arthritis by ex vivo extracellular superoxide dismutase gene transfer.

Iyama S, Okamoto T, Sato T, Yamauchi N, Sato Y, Sasaki K, Takahashi M, Tanaka M, Adachi T, Kogawa K, Kato J, Sakamaki S, Niitsu Y

Arthritis and rheumatism 44 ( 9 ) 2160 - 2167 2001.09 [Refereed]

PubMed CiNii

Hepatic and splenic arterial infusion chemotherapy after transcatheter peripancreatic arterial embolization for patients with inoperable adenocarcinoma of the pancreas

H. Homma, T. Kukitsu, S. Mezawa, T. Doi, M. Kida, K. Miyanishi, K. Takada, K. Murase, S. Iyama, Y. Niitsu

Gan to kagaku ryoho. Cancer & chemotherapy 28 ( 11 ) 1558 - 1561 2001

Thirty-one patients with advanced pancreatic carcinoma and liver metastases were treated by hepatic and splenic arterial infusion chemotherapy after transcatheter peripancreatic arterial embolization. The response rate for these 31 patients was 61.3%, with a mean survival period of 17.8 +/- 3.2 months and a 50% survival period of 12 months. By site of the primary tumor, the response rate for pancreatic head and body carcinoma was 81%, with a mean survival period of 21.6 +/- 4.0 months and a 50% survival period of 17 months, whereas the response rate for pancreatic caudal carcinoma was 20%, with a mean survival period of 6.1 +/- 0.5 months and a 50% survival period of 6 months. We believe that the current chemotherapy is an effective treatment for advanced pancreatic cancer with liver metastases.

PubMed

Implantation of a dual chambers port for hepatic and splenic arterial infusion chemotherapy in advanced pancreatic carcinoma with multiple liver metastasis

T. Kukitsu, H. Homma, S. Iyama, T. Doi, M. Kida, S. Mezawa, K. Murase, K. Takada, K. Miyanishi, Y. Niitsu

Gan to kagaku ryoho. Cancer & chemotherapy 28 ( 11 ) 1562 - 1564 2001

PubMed

Synergistic suppressive effect of double transfection of tumor necrosis factor-alpha and interleukin 12 genes on tumorigenicity of Meth-A cells

H Fujiwara, N Yamauchi, Y Sato, K Sasaki, M Takahashi, T Okamoto, T Sato, S Iyama, Y Koshita, M Hirayama, H Yamagishi, Y Niitsu

JAPANESE JOURNAL OF CANCER RESEARCH ( BUSINESS CENTER ACADEMIC SOCIETIES JAPAN ) 91 ( 12 ) 1296 - 1302 2000.12 [Refereed]

Tumor necrosis factor-alpha (TNF-alpha) and interleukin 12 (IL-12), both potent antitumor cytokines, are known to be involved in the host's antitumor immune surveillance in tumor bearers, via different mechanisms. The former enhances the activities of dendritic cells, natural killer/lymphocyte-activated killer (NK/LAK) and cytotoxic T lymphocyte (CTL), while the latter induces Th1-type cellular immunity and enhances the activities of natural killer T (NKT), NK/LAK and CTL. In the present study, in the expectation of synergistic actions of these cytokines in stimulating the host's immune responses, we investigated the feasibility of a cancer vaccine involving double transfection with both genes in a murine model. The expression of major histocompatibility complex (MHC) class I, class II and B7.1 on the surface of the double transfectants was enhanced as revealed by FACS analysis. A significant decrease in tumorigenicity was observed in mice inoculated with the double transfectants. Cytotoxicity assay revealed that the activities of NK/LAK and CTL from spleens of mice bearing the double transfectants were enhanced. The induction of tumor-specific immunity was confirmed by rechallenge with parental Meth-A cells in mice that had rejected the double transfectants. Thus, double transfection of TNF-alpha and IL-12 genes was considered to bring about synergistic suppressive effects on the tumorigenicity of transfectants through the activation of killer cells by produced cytokines and the enhancement of expression of MHC class I, II and B7.1 molecules.

A case of type IIa autoimmune hepatitis showing fluctuation of serum CA 19-9 level

T. Sato, J. Kato, Y. Sato, S. Iyama, K. Takada, S. Hagiwara, S. Takahashi, H. Kuroda, S. Mezawa, Y. Koshita, N. Yoshizaki, M. Takahashi, S. Sakamaki, Y. Niitsu

Acta Hepatologica Japonica ( Japan Society of Hepatology ) 41 ( 9 ) 654 - 659 2000 [Refereed]

DOI

CD4,CD8 double negative T-CLLの1例

山内尚文, 高張大亮, 井山諭, 大久保俊一, 佐々木紀幸, 河野豊, 佐藤勉, 加藤淳二, 坂牧純夫, 新津洋司郎

臨床血液 ( (一社)日本血液学会-東京事務局 ) 40 ( 9 ) 901 - 901 1999.09 [Refereed]

Suicide gene therapy using transferrin (Tf)-HSV-TK-gene conjugate

J. Fukaura, Y. Sato, K. Sasaki, M. Takahashi, T. Okamoto, T. Sato, S. Iyama, N. Yamauchi, Y. Niitsu

Biotherapy 13 ( 5 ) 625 - 627 1999

The transferrin receptor (Tf-R) is universally present on the surface of actively proliferating cells such as tumor cells and recycles back to the cell surface after it is bound with ligand (Tf) and is internalized. The gene conjugated with Tf therefore may be preferentially delivered to the tumor cells in vivo. In the present study, we employed a stepwise solid phase method on preparing Tf-avidin-biotin-DNA complex, using affinity chromatography, which keeps the receptor binding motif of Tf-R affinity intact. The conjugate constructed by this method was shown to provide a high transfection efficiency in vitro against tumor cells and a specific delivery of the gene to tumor tissue in vivo. Furthermore, we investigated the therapeutic effects of a suicide gene therapy of metastatic K562 cells in SCID mice using Tf-HSV-TK-gene conjugate and GCV treatment. An appreciable suppression of metastasis was observed as well as prolongation of survivals. These results indicated that the suicide gene therapy using Tf-HSV-TK-gene conjugate was shown to provide a specific delivery of the gene to tumor tissue in vivo and the potential for tumoricydal therapy.

Gene therapy for gastrointestinal cancer using adenovirus-mediated TNF receptor-p55 gene transfer followed by systemic TNF administration

M. Takahashi, N. Yamauchi, K. Sasaki, S. Iyama, Y. Yamada, T. Okamoto, Y. Sato, T. Sato, H. Sasaki, T. Hagino, Y. Niitsu

Biotherapy 12 ( 5 ) 583 - 585 1998

We have shown that local administration of TNF for advanced gastrointestinal cancers resistant to conventional treatments could induce tumor necrosis and reduce tumor markers. But no complete regression was obtained. In order to improve the therapeutic efficacy of TNF, we have investigated the augmentation of susceptibility to TNF by transduction of TNF-receptor p55 (TNFR-p55) gene, which is responsible for cytotoxicity of TNF, to pancreatic cancer cells. We previously showed that the tumor volume of TNFR-p55 gene transduced stable transformant could be reduced by systemic administration of TNF. But it is not a practical model to investigate augmentation of anti-tumor effects of TNF by transduction of TNFR-p55 gene. We applied this strategy for in vivo gene therapy for formed tumor to use replication deficient adenovirus vector expressing TNFR-p55. TNF-resistant hepatocellular carcinoma cell line (PLC/PRF/5) and colon cancer cell line (M7609) were rendered to TNF-susceptible tumor with TNF dose-dependency after AdCMV/TNFR-p55 infection in vitro. Furthermore these formed tumor were regressed by adenovirus-mediated TNFR-p55 gene transfer in vivo followed by systemic administration of TNF. Median survival was significantly prolonged with TNFR-p55 gene transfer in vivo followed by systemic administration of TNF compared with no therapy. We could also show the possibility of novel suicide-immunogenetherapy transducing TNFR-p55 gene in vivo followed by TNF administration.

Involvement of ICE-like protease and oxygen free radicals in tumor- necrosis-factor-mediated apoptosis

S. Iyama, N. Yamauchi, T. Sato, T. Okamoto, H. Sasaki, M. Takahashi, Y. Sato, T. Hagino, D. Kobayashi, N. Watanabe, Y. Niitsu

Biotherapy 12 ( 5 ) 691 - 693 1998

In the present study, we demonstrated the relationship of caspases (CPP32) and OFRs on TNF-induced apoptosis signal. The increase of OFRs production was dependent on the concentration of TNF, and TNF susceptibility was significantly correlated with the production of OFRs on human leukemic cell lines. NAC inhibited the TNF-induced OFRs production, and 100 μM of Ac- DEVD-cho, which is a specific inhibitor of CPP32, inhibited the production of OFRs completely. NAC inhibited the fragmentation of DNA induced by TNF. TNF enhanced the expression of CPP32 mRNA, and there was no effect by addition of NAC. TNF-induced CPP32 activation was suppressed by addition of Ac-DEVD-cho, but showed no significant change when treated with NAC. These results suggest that TNF can induce apoptosis by induction of enhancement of caspase, especially CPP32, and production of OFRs sequentially.

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