論文 - 井山　諭

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年

　概要を見る

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年

　概要を見る

Dual chambers ports were implanted in 7 patients with advanced pancreatic carcinoma and metastatic liver tumors to connect a 3.3 Fr catheter as an indwelling catheter. In comparison with the implantation of a pair of Single chamber ports, implanting a Dual chambers port entails some technical difficulties, but has some benefits in terms of stabler placement, a smaller incision, reduction of medical fees, and improved QOL of patients.

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年12月  [査読有り]

　概要を見る

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年  [査読有り]

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年09月  [査読有り]

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年

　概要を見る

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年

　概要を見る

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年

　概要を見る

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.