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2001年５月１日 札幌医科大学 2000-2001 年報のための原稿 氏名：濱田洋文 HAMADA HIROFUMI 所属： 札幌医科大学医学部分子医学研究部門 医学研究科分子器官制御医学 遺伝子医学領域 分子医学・遺伝子治療学 Sapporo Medical University School of Medicine,
Department of Molecular Medicine Graduate School of Medicine, Program of Molecular
and Organ Regulation, Division
of Genetic
Medicine, Molecular Medicine
and Gene Therapy 学位：MD(1981), PhD(Medical Science 1987) 専門分野：Molecular Medicine 研究テーマ：再生医学 遺伝子治療 幹細胞 研究活動と展望 分子医学研究部門は、癌をはじめとした難病の本質的な治療法の開発に取り組み、遺伝子治療・再生医療の研究の大きな流れを形成してゆけるような、基礎と臨床の橋渡しとなる研究室造りをめざしている。遺伝子治療・再生医療の先端的研究を進めることを通じて、大学院の教育研究活動の充実化を図っている。当部門の研究の流れは以下のようになる： １）細胞や組織の培養・分化制御、遺伝子導入発現法の基盤技術の開発。 ２）難治疾患の治療のポイントとなる病態の解明。 ３）実験動物モデルによる治療実験。 難治疾患を実際に治癒させうる再生医療、遺伝子治療法の樹立をめざし、臨床グループとの共同研究、遺伝子治療臨床研究に意欲的に取り組んでいる。 キーワード： 再生医学 遺伝子治療 幹細胞 学術文献（原著、総説、著書）： （平成2001年3月までの過去1年間、in pressも含む。） 1. 原著（計44編） Kawamura, K., Tasaki, K., Hamada, H., Takenaga,
K., Sakiyama, S. and Tagawa, M.
Expression of Escherichia coli uracil phosphoribosyltransferase
gene in murine colon carcinoma cells augments
the antitumor effect of 5-fluorouracil and
induces protective immunity. Cancer
Gene Therapy 7(4):637-643, 2000. 2. Sunamura, M., Sun, L., Lozonschi, L., Duda.
D.G., Kodama, T., Matsumoto, G., Shimamura,
H., Kobari, M., Hamada, H., and Matsuno,
S. The anti-angiogenesis effect of
IL-12 during early growth of human pancreatic
cancer in SCID mice. Pancreas
20(3): 227-33, 2000. 3. Shinoura N, Yamamoto N, Yoshida Y, Fujita
T, Saito N, Asai A, Kirino T, Hamada H.
Adenovirus-mediated gene transduction of
IkappaB or IkappaB plus Bax gene drastically
enhances tumor necrosis factor (TNF)-induced
apoptosis in human gliomas. Jpn J Cancer
Res. 91(1):41-51, 2000. 4. Koyama, F., Sawada, H., Fujii, H., Hirao,
T., Ueno, M., Hamada, H., and Nakano, H.
The enzyme/prodrug gene therapy for human
colon cancer cells using adenovirus-mediated
transfer of Escherichia coli cytosine deaminase
gene driven by the CAG promoter associated
with 5-fluorocytosine administration.
J. Exp.Clin. Cancer Res. (JECCR) 19(1): 75-80,
2000. 5. Shinoura, Yoshida, Y., Asai, A., Kirino,
T., and Hamada, H. Adenovirus-mediated transfer
of p53 and Fas ligand drastically enhances
apoptosis in gliomas. Cancer Gene Ther. 7(5):
732-738, 2000. 6. Shinoura, Saito, K., Yoshida, Y., Hashimoto,
M., Asai, A., Kirino, T., and Hamada, H.
Adenovirus-mediated transfer
of Bax with caspase-8 controlled by myelin
basic protein promoter induces enhanced apoptosis
in gliomas. Cancer Gene Ther. 7(5):
739-748, 2000. 7. Motoi, F., Sunamura, M., Ding, L., Duda,
DG., Yoshida, Y., Zhang, W-P., Matsuno, S.,
and Hamada, H. Effective gene therapy for
pancreatic cancer by cytokines mediated by
restricted replication-competent adenovirus.
Human Gene Ther. 11(2): 223-235, 2000. 8. Shinoura, N., Satou, R., Yoshida, Y., Asai,
A., Kirino, T., and Hamada, H. Adenovirus-mediated
transfer of Bcl-xl protects neuronal cells
from Bax-induced apoptosis. Exp. Cell
Res. 254(2): 221-231, 2000. 9. Narita, M., Takanaga, K., Yoshida, Y., Kadomatsu,
K., Muramatsu, T., Matsubara, S., Hamada,
H., Goto, S., Saisho, H., Sakiyama, S. and
Tagawa, M.: Polyadenylation signal facilitates
the expression of foreign gene that is driven
by an internal promoter located in the reverse
orientation to long terminal repeat of retrovirus.
Anticancer Res. 20(1A): 279-82, 2000. 10. Qiu, JH, Asai, A, Chi, S., Saito, N., Hamada,
H., and Kirino, T. Protease inhibitors
induce cytochrome c-caspase-3-like protease-mediated
apoptosis in cultured cortical neurons.
J. Neuroscience 20 (1): 259-265, 2000. 11. Kobayashi, T., Okamoto, Nakazawa, M., K.,
Kobata, T., Hasunuma, T., Kato, T., Hamada,
H., and Nishioka, K. Novel gene therapy
for rheumatoid arthritis by FADD gene transfer:
Induction of apoptosis of rheumatoid synoviocytes
but not chondrocytes. Gene Ther. 7(6):
527-33, 2000. 12. Kasaoka, Y., Nakamoto, T., Wang, J., Usui,
T., and Hamada, H. Gene therapy for
murine renal cell carcinoma using Genetically
engineered tumor cells to secrete interleukin-12.
Hiroshima J. Med. Sci. 49(1): 29-35,
2000. 13. Adachi Y, Tamiya T, Ichikawa T, Terada K,
Ono Y, Matsumoto K, Furuta T, Hamada H, Ohmoto
T Experimental gene therapy for
brain tumors using adenovirus-mediated transfer
of cytosine deaminase gene and uracil phosphoribosyltransferase
gene with 5-fluorocytosine. Hum Gene
Ther 11(1): 77-89, 2000. 14. Kobayashi, T., Okamoto, K., Kobata, T., Hasunuma,
T., Kato, T., Hamada, H., and Nishioka, K.
Differential regulation of Fas-mediated apoptosis
of rheumatoid synoviocytes by TNFa and bFGF
is associated with the expression of apoptosis-related
molecules. Arthritis & Rheumatism
43(5):1106-1114, 2000. 15. Wang, J., Nakamoto, T., Kasaoka, Y., Usui,
T., and Hamada, H. Antitumor effect
of murine renal cell carcinoma cells genetically
modified to express B7-1 combined with cytokines
secreting fibroblasts. Hiroshima J.
Med. Sci. 49(1): 73-82, 2000. 16. Shinoura, N., Muramatsu, Y., Yoshida, Y.,
Asai, A., Kirino, T., and Hamada, H.
Adenovirus-mediated transfer of caspase-3
with Fas ligand Induces drastic apoptosis
In U373MG glioma cells. Exp. Cell Res. 256(2):423-433.,
2000. 17. Koyama, F., Sawada, H., Hirao, T., Fujii,
H., Hamada, H., and Nakano, H.
Combined suicide gene therapy for human colon
cancer cells using adenovirus-mediated
transfer of Escherichia coli cytosine deaminase
gene Escherichia coli uracil phosphoribosyltransferase
gene with 5-fluorocytosine.
Cancer Gene Ther. 7(7):1015-1022, 2000. 18. Shinoura, N., Yoshida, Y., Asai, A., Kirino,
T., and Hamada, H. Adenovirus-mediated
transfer of caspase-8 augments cell death
in gliomas: Implication for gene therapy.
Hum. Gene Ther 11(8):1123-1137, 2000. 19. Ju DW, Tao Q, Cheng DS, Zhang W, Zhang M,
Hamada H, Cao X. Adenovirus-mediated
lymphotactin gene transfer improves therapeutic
efficacy of cytosine deaminase suicide gene
therapy in established murine colon carcinoma.
Gene Ther. 7(4):329-38, 2000. 20. Kimura H, Sakata Y, Hamada H, Yoshida Y,
Sato O, Deguchi J, Sugawara Y, Makuuchi M,
Miyata T. In vivo retention of endothelial
cells adenovirally transduced with tissue-type
plasminogen activator and seeded onto expanded
polytetrafluoroethylene. J. Vascular
Surgery. 32(2): 353-363, 2000. 21. Kosuga, M., Takahashi, S., Sasaki, K., Li, XK., Fujino, M., Hamada, H., Suzuki, S., Yamada, M., Matsuo,Y., and Okuyama,
T. Adenovirus-Mediated Gene Therapy for
Mucopolysaccharidosis Vll:Involvement of
Cross-Correction in Wide-Spread Distribution
of the Gene Products and Long-Term Effects
of CTLA-4Ig. Molecular Therapy. 1(5): 406-413,
2000. 22. Shinoura, S., Yamamoto, N., Yoshida, Y.,
Asai, A., Kirino, T., and Hamada, H.
Adenovirus-mediated transfer of caspase-8
in combination with super-repressor of NF-kB
drastically induced apoptosis in gliomas.
Biochem. Biophys. Res. Commun. 271(2):
544-552, 2000. 23. Kiyoko Kawamura, Hiroki Namba, Rumana Bahar,
Motohiro Miyauchi, Tomoko Maeda, Hirofumi
Hamada, Shigeru Sakiyama, Masatoshi Tagawa
Transduction of the human deoxycytidine kinase
gene in rodent tumor cells induces in vivo
growth retardation in syngeneic hosts.
Cancer Letters. 156(2):151-157, 2000. 24. Shiota G, Kunisada T, Oyama K, Udagawa A,
Nomi T, Tanaka K, Tsutsumi A, Isono M, Nakamura
T, Hamada H, Sakatani T, Sell S, Sato K,
Ito H, Kawasaki H. In vivo transfer
of hepatocyte growth factor gene accelerates
proliferation of hepatic oval cells in a
2-acetylaminofluorene/partial hepatectomy
model in rats. FEBS Lett.
470(3):325-330, 2000. 25. Cao X, Huang X, Ju DW, Zhang W, Hamada H,
Wang J. Enhanced antitumoral effect
of adenovirus-mediated cytosine deaminase
gene therapy by induction of antigen-presenting
cells through stem cell factor/granulocyte-macrophage
colony-stimulating factor gene transfer.
Cancer Gene Ther. 7(2):177-86, 2000. 26. Shinoura, N., Sakurai, S., Asai, A., Kirino,
T., and Hamada, H. Transduction
of Apaf-1 or caspase-9 induces apoptosis
in A172 cells, which are resistant to p53-mediated
apoptosis. Biochem. Biophys.
Res. Commun. 272(3): 667-673, 2000. 27. Lei H, Ju DW, Yu Y, Tao Q, Chen G, Gu S,
Hamada H, Cao X. Induction of potent
antitumor response by vaccination with tumor
lysate-pulsed macrophages engineered to secrete
macrophage colony-stimulating factor and
interferon-gamma. Gene Ther. 7(8):707-13,
2000. 28. Tani K, Nakazaki Y, Hase H, Takahashi K,
Azuma M, Ohata J, Kitamura
R, Komine F, Oiwa M, Masunaga A, Maekawa
T, Satoh N, Adachi D, Soda Y, Machida U,
Endo M, Yamazaki T, Watari K, Tojo A, Yamashita
N, Tomikawa S, Eriguchi M, Hamada H, Wakumoto
Y, Hanazawa K, Okumura K. Progress reports
on immune gene therapy for stage IV renal
cell cancer using lethally irradiated granulocyte-macrophage
colony-stimulating factor-transduced autologous
renal cancer cells. Cancer Chemother
Pharmacol. 46 Suppl:S73-6, 2000. 29. Matsuoka N, Miyatake S, Yukawa H, Takahashi
JC, Saiki M, Mori H, Ishii K, Akimoto M,
Hamada H, Hashimoto N. Adenovirus-mediated
gene transfer of basic fibroblast growth
factor promotes the survival of primary-cultured
rat neuronal cells. Neuroreport. 11(9):
2001-6, 2000. 30. Shinoura N, Yamamoto N, Asai A, Kirino T,
and Hamada H. Adenovirus-mediated Transfer
of Fas Ligand Gene Augments Radiation-induced
Apoptosis in U-373MG Glioma Cells.
Jpn J Cancer Res. 91(10):1044-1050, 2000. 31. Shinoura N, Sakurai S, Asai A, Kirino T,
and Hamada H. Transduction of a Fiber-mutant
Adenovirus for the HSVtk Gene Highly Augments
the Cytopathic Effect towards Gliomas.
Jpn J Cancer Res. 91(10):1028-1034, 2000. 32. Hayashi S, Dai-Kaku L, Namii Y, Kato T, Tokoro
T, Kobayashi T, Yokoyama I, Hamada H, Nakao
A. Effectiveness of adenovirus-mediated
gene transfer with CTLA4Ig in allo and xeno-transplantation.
Transplant Proc. 32(7): 2520-2521, 2000.
33. Hayashi S, Guang-Lin M, Yokoyama I, Namii
Y, Hamada H, Nakao A. Adenovirus-mediated
gene transfer of CTLA4Ig gene results in
prolonged survival of heart allograft. Transpl
Int. 13 Suppl 1:S329-32, 2000. 34. Seino K, Tun T, Ohshima N, Hamada H, Yoshino
K, Ikeda S, Fukunaga K, Taniguchi H, Takada
Y, Yuzawa K, Otsuka M, Todoroki T, Fukao
K. Inhibition of CD95 ligand-mediated
inflammation. Transplant Proc. 32(7): 2038-2039,
2000. 35. Shinoura N, Muramatsu Y, Asai A, Han S, Horii
A, Kirino T, Hamada H. Degree of apoptosis
induced by adenovirus-mediated transduction
of p53 or p73alpha depends on the p53 status
of glioma cells Cancer Lett. 160(1): 67-73,
2000. 36. Koyama F, Sawada H, Fujii H, Hamada H, Hirao
T, Ueno M, Nakano H. Adenoviral-mediated
transfer of escherichia coli uracil phosphoribosyltransferase
(UPRT) gene to modulate the sensitivity of
the human colon cancer cells to 5-fluorouracil
Eur J Cancer. 36(18): 2403-10, 2000. 37. Kawamura, K., Bahar, R., Namba, H., Seimiya,
M., Takenaga, K., Hamada, H., Sakiyama,
S. and Tagawa, M.: Bystander effect in uracil
phosphoribosyltransferase/5-fluorouracil-mediated
suicide gene therapy is correlated with the
level of intercellular communication.
Int. J. Oncology in press, 2001. 38. Lin Hui Wang, Dian Wen Ju, Yinghao Sun, Qun
Tao, Songxi Qian, Jing Mi, Hirofumi Hamada,
Xuetao Cao The potent antitumor effects
of combined p16 gene and GM-CSF gene therapy
through efficient induction of antitumor
immunity J Cancer Res Clin Oncol.
127: 101-108, 2001. 39. Nagayama Y, Nishihara E, Namba H, Yokoi H,
Hasegawa M, Mizuguchi H, Hayakawa T, Hamada
H, Yamashita S, Niwa M. Targeting the replication
of adenovirus to p53-defective thyroid carcinoma
with a p53-regulated Cre/loxP system.
Cancer Gene Ther. 8(1):36-44, 2001. 40. Wang LH, Ju DW, Sun Y, Tao Q, Qian S, Mi
J, Hamada H, Cao X The potent
antitumor effects of combined p16 gene and
GM-CSF gene therapy through efficient induction
of antitumor immunity. J Cancer Res
Clin Oncol. 127(2):101-108, 2001. 41. Shinohara T, Miki T, Nishimura N, Nokihara
H, Hamada H, Mukaida N, Sone S. Nuclear
factor-kappaB-dependent expression of metastasis
suppressor KAI1/CD82 gene in lung cancer
cell lines expressing mutant p53. Cancer
Res. 2001 61(2):673-8. 42. Ding, L-H, Iimura, E., Saijo, K, Hamada,
H., and Ohno, T. A speedy method to
detect inserted DNA fragment in cell lines
transfected with retrovirus vectors.
Cytotechnology 34: 243-252, 2000. 43. Sugibayashi, R., Shimizu, T., Suzuki, T.,
Yamamoto, N., Hamada, H., and Takeda, K.
Upregulation of p21(WAF1/CIP1) leads to morphologic
changes and esterase activity in TPA-mediated
differentiation of human prostate cancer
cell line TSU-Pr1. Oncogene. 20(10):1220-1228,
2001. 44. Shimizu, T., Shimada, H., Ochiai, T., and Hamada, H. Enhanced growth suppression in esophageal carcinoma cells using adenovirus-mediated fusion gene transfer (uracl phosphoribosyl-transferase and herpes simplex virus thymidine kinase). Cancer Gene Therapy, in press, 2001.
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近況と話題 最新 近況と話題 03/04/21 〜 |
