Usefulness of BIACORE technology for the development of telomere/telomerase-targeted therapies
Project/Area Number |
15591432
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Digestive surgery
|
Research Institution | Iwate medical University School of Medicine |
Principal Investigator |
SHIDA Kaorul Iwate Med. Univ. School of Med., Dept. of Surg., Assistant Professor, 医学部, 助教授 (70146041)
|
Co-Investigator(Kenkyū-buntansha) |
MAESAWA Chihaya Iwate Med. Univ. School of Med., Dept. of Surg., Assistant Professor, 医学部, 助教授 (10326647)
|
Project Period (FY) |
2003 – 2004
|
Project Status |
Completed (Fiscal Year 2004)
|
Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2003: ¥3,300,000 (Direct Cost: ¥3,300,000)
|
Keywords | Stem cell / hTERT / TRE assay / Replicative senescence / Estradiol / Biomolecular ineraction / Telomere / Telomerase / テロメラーゼ / テロメア / ARK / G-quardplex / 分子標的治療薬 / 分子標的治療 / TRE assay / 生体内分子間相互作用解析装置 |
Research Abstract |
The telomere is a special cap? like structure at the end of eukaryotic chromosomes, composed of tandem TTAGGG repeats. Telomere length is maintained by a balance between two mechanism: elongation (telomerase) and shortening (end-replication problem) of hexameric repeats. We think that telomerase and telomere structure become potentially important treatment targets for cancer therapy. We have recently developed the telomeric repeat elongation (TRE) assay, a rapid biosensor chip assay using surface plasmon resonance (SPR), for the quantitative assessment of telomerase activity. We have recently focused on the telomerase catalytic subunit (human telomerase reverse transcriptase: hTERT) as a target of telomerase therapy. It is well known that estrogen activates telomerase via a direct effect on the hTERT promoter. In fact, breast cancer cell lines have greater telomerase activity than other types of cancer cell lines. We evaluated the inhibitory effects of tamoxifen (TAM, an anti-estrogen agent), which acts competitively on the estrogen response element (ERE) at the hTERT promoter. TAM decreased the telomerase activity of breast cancer cell lines by approximately 50%, although the down-regulated level was insufficient to achieve cellular senescence or crisis. We have also applied the BIACORE apparatus for screening telomerase inhibitors. The G?quadruplex structure is a suitable target for telomere/telomerase?targeted therapy in the development of a new cancer treatment strategy. To investigate the inhibitory effects of G-quadruplex-mediated telomerase inhibitors, we performed a kinetic assay using the BIACORE apparatus. Rate constants for the interaction of each compound with telomeric DNA were well correlated with the inhibitory effects of telomerase activity evaluated by the TRE assay. Kinetic and TRE assays using SPR technology will be useful for seeking new telomerase inhibitors for molecular target therapy.
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Report
(3 results)
Research Products
(52 results)
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[Journal Article] Epigenetic status and aberrant expression of the maspin gene in human hepato-biliary tract carcinomas.2005
Author(s)
Fujisawa K, Maesawa C, Sato R, Wada K, Ogasawara S, Akiyama Y, Takeda M, Fujita T, Otsuka K, Higuchi T, Suzuki K, Saito K, Masuda T
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Journal Title
Lab Invest 85
Pages: 214-224
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Consensus JH gene probes with conjugated 3'-minor groove binder for monitoring minimal residual disease in acute lymphoblastic leukemia.2005
Author(s)
Uchiyama M, Maesawa C, Yashima-Abo A, Tarusawa M, Endo M, Sugawara W, Chida S, Onodera S, Tsukushi Y, Ishida Y, Tsuchiya S, Masuda T.
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Journal Title
J Mol Diagn 7
Pages: 121-126
Description
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[Journal Article] Infrequent mutation of the human envoplakin gene is closely linked to the tylosis oesophageal cancer locus in sporadic oesophageal squamous cell carcinomas.2005
Author(s)
Iwaya T, Maesawa C, Kimura T, Ogasawara S, Ikeda K, Kimura Y, Noda Y, Ishida K, Sato N, Saito K, Masuda T.
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Journal Title
Oncol Rep 13
Pages: 703-707
Description
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[Journal Article] Epigenetic status and aberrant expression of the maspin gene in human hepato-biliary tract carcinomas.2005
Author(s)
Fujisawa K, Maesawa C, Sato R, Wada K, Ogasawara S, Akiyama Y, Takeda M, Fujita T, Otsuka K, Higuchi T, Suzuki K, Saito K, Masuda T.
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Journal Title
Lab Invest. Feb 85(2)
Pages: 214-24
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Consensus JH gene probes with conjugated 3'-minor groove binder for monitoring minimal residual disease in acute lymphoblastic leukemia.2005
Author(s)
Uchiyama M, Maesawa C, Yashima-Abo A, Tarusawa M, Endo M, Sugawara W, Chida S, Onodera S, Tsukushi Y, Ishida Y, Tsuchiya S, Masuda T.
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Journal Title
J Mol Diagn. Feb;7(1)
Pages: 121-6
Description
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[Journal Article] Infrequent mutation of the human envoplakin gene is closely linked to the tylosis oesophageal cancer locus in sporadic oesophageal squamous cell carcinomas.2005
Author(s)
Iwaya T, Maesawa C, Kimura T, Ogasawara S, Ikeda K, Kimura Y, Noda Y, Ishida K, Sato N, Saito K, Masuda T.
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Journal Title
Oncol Rep. Apr 13(4)
Pages: 703-7
Description
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[Journal Article] Infrequent mutation of the human envoplakin gene closely linked to the tylosis oesophageal cancer (TOC) locus in sporadic oesophageal squamous cell carcinomas.2005
Author(s)
Iwaya T, Maesawa C.Uesugi N, Kimura T, Ogasawara, Ikeda K, Kimura Y, Mitomo S, Ishida K, Sato N, Saito K, Masuda T.
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Journal Title
Oncol Rep 13・4
Pages: 703-707
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[Journal Article] Development of immunoglobulin variable heavy chain gene consensus probes with conjugated 3' minor groove binder groups for monitoring minimal residual disease in childhood acute lymphoblastic leukaemia.2004
Author(s)
Uchiyama M, Maesawa C, Yashima A, Itabashi T, Satoh T, Tarusawa M, Endo M, Takahashi Y, Sasaki S, Tsuchiya S, Ishida Y, Masuda T.
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Journal Title
J Clin Pathol 56
Pages: 952-955
Description
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[Journal Article] Surgery plus chemotherapy compared with surgery alone for localized squamous cell carcinoma of the thoracic esophagus : a Japan Clinical Oncology Group Study-JCOG 9204.2004
Author(s)
Ando N, Iizuka T, Ide H, Ishida K, Shinoda M, Nishimaki T, Takiyama W, Watanabe H, Isono K, Aoyama N, Makuuchi H, Tanaka O, Yamana H, Ikeuchi S, Kabuto T, Nagai K, Shimada Y, Kinjo Y, Fukuda H, Japan Clinical Oncology Group.
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Journal Title
J Clin Oncol 21
Pages: 4592-4596
Description
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[Journal Article] Disruption of cell-type-specific methylation at the Maspin gene promoter is frequently involved in undifferentiated thyroid cancers.2004
Author(s)
Ogasawara S, Maesawa C, Yamamoto M, Akiyama Y, Wada K, Fujisawa K, Higuchi T, Tomisawa Y, Sato N, Endo S, Saito K, Masuda T.
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Journal Title
Oncogene 523
Pages: 1117-1124
Description
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[Journal Article] Human PinX1,a patent telomerase inhibitor, is not involved in human gastrointestinal tract carcinoma.2004
Author(s)
Akiyama Y, Maesawa C, Wada K, Fujisawa K, Itabashi T, Noda Y, Honda T, Sato N, Ishida K, Takagane A, Saito K, Masuda T.
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Journal Title
Oncol Rep.2004 Apr;11(4):871-4. 11
Pages: 871-874
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[Journal Article] Short consensus probes with 3'-minor groove binder of the immunoglobulin heavy-chain gene for real-time quantitative PCR in B-cell non-Hodgkin lymphomas.2004
Author(s)
Uchiyama M, Maesawa C, Yashima-Abo A, Tarusawa M, Satoh M, Satoh T, Ishida Y, Ito S, Murai K, Enomoto S, Utsugisawa T, Masuda T.
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Journal Title
Lab Invest.2004 Jul;84(7):932-6. 84
Pages: 932-936
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[Journal Article] Acute renal failure due to leukemic cell infiltration followed by relapseat multiple extramedullary sites in a child with acute lymphoblastic leukemia.2004
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Sato A, Imaizumi M, Shikaoka S, Niizuma H, Hoshi Y, Takeyama J, Fuji K, Nishio T, Watanabe M, Maesawa C, Hayashi Y, Iinuma K.
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Journal Title
Leuk Lymphoma 45
Pages: 825-828
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[Journal Article] Disruption of cell-type-specific methylation at the Maspin gene promoter is frequently involved in undifferentiated thyroid cancers.2004
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Ogasawara S, Maesawa c, Yamamoto M, Akiyama Y, Wada K, Fujisawa K, Higuchi T, Tomisawa Y, Sato N, Endo S, Saito K, Masuda T.
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Oncogene. Feb 5:23(5)
Pages: 1117-24
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[Journal Article] Human PinX1, a potent telomerase inhibitor, is not involved in human gastrointestinal tract carcinoma.2004
Author(s)
Akiyama Y, Maesawa C, Wada K, Fujisawa K, Itabashi T, Noda Y, Honda T, Sato N, Ishida K, Takagane A, Saito K, Masuda T.
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Journal Title
Oncol Rep. Apr,11(4)
Pages: 871-4
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[Journal Article] Short consensus probes with 3'-minor groove binder of the immunoglobulin heavy-chain gene for real-time quantitative PCR in B-cell non-Hodgkin lymphomas.2004
Author(s)
Uchiyama M, Maesawa C, Yashima-Abo A, Tarusawa M, Satoh M, Satoh T, Ishida Y, Ito S, Murai K, Enomoto S, Utsugisawa T, Masuda T.
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Lab Invest. Jul,84(7)
Pages: 932-6
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[Journal Article] Acute renal failure due to leukemic cell in filtration followed by relapse at multiple extramedullory sites in a child with acute lymphoblastic leukemia.2004
Author(s)
Sato A, Imaizumi M, Chikaoka S, Niizuma H, Hoshi Y, Takeyama J, Fuji K, Nishio T, Watanabe M, Maesawa C, Hayashi Y, Iinuma K.
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Journal Title
Leuk Lymphoma. Apr 45(4)
Pages: 825-8
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[Journal Article] Disruption of cell-type-specific methylation at the Maspin gene promoter is frequently involved in undifferentiated thyroid cancers.2004
Author(s)
Ogasawara S, Maesawa C, Yamamoto M, Akiyama Y, Wada K, Fujisawa K, Higuchi T, Tomisawa Y, Sato N, Endo S, Saito K, Masuda T.
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Journal Title
Oncogene 23・5
Pages: 1117-1124
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[Journal Article] Human PinX1, a potent telomerase inhibitor, is not involved in human gastrointestinal tract carcinoma2004
Author(s)
Akiyama Y, Maesawa C, Wada K, Fujisawa K, Itabashi T, Noda Y, Honda T, Sato N, Ishida K, Takagane A, Saito K, Masuda T
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Oncol Rep 11・4
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[Journal Article] Quantitative assessment of contaminating tumor cells in autologous peripheral blood stem cells of B-cell non-Hodgkin lymphomas using immunoglobulin heavy chain gene allele-specific oligonucleotide real-time quantitative-polymerase chain reaction.2003
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Yashima A, Maesawa C, Uchiyama M, Tarusawa M, Satoh T, Satoh M, Enomoto S, Sugawara K, Numaoka H, Murai K, Utsugisawa T, Ishida Y, Masuda T.
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Leuk Res 27
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[Journal Article] Development of consensus flucreogenically labeled probes of the immunoglobulin heavy-chain gene for detecting minimal residual disease in B-cell non-Hodgkin lymphomas.2003
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Uchiyama M, Maesawa C, Yashima A, Tarusawa M, Satoh T, Ishida Y, Ito S, Murai K, Enomoto S, Utsugisawa T, Motoyoshi K, Masuda T.
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Cance Sci 94
Pages: 877-885
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[Journal Article] Quantitative assessment of contaminating tumor cells in autologous peripheral blood stem cells of B-cell non-Hodgkin lymphomas using immunoglobulin heavy chain gene allele-specific oligonucleotide real-time quantitative-polymerase chain reaction.2003
Author(s)
Yashima A, Maesawa C, Uchiyama M, Tarusawa M, Satoh T, Satoh M, Enomoto S, Sugawara K, Numaoka H, Murai K, Utsugisawa T, Ishida Y, Masuda T.
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Journal Title
Leuk Res. Oct 27(10)
Pages: 925-34
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[Journal Article] Development of consensus fluorogenically labeled probes of the immunoglobulin heavy-chain gene for detecting minimal residual disease in B-cell non-Hodgkin lymphomas.2003
Author(s)
Uchiyama M, Maesawa C, Yashima A, Tarusawa M, Satoh T, Ishida Y, Ito S, Murai K, Enomoto S, Utsugisawa T, Motoyoshi K, Masuda T.
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Cancer Sci. Oct 94(10)
Pages: 877-85
NAID
Description
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[Journal Article] Development of immunoglobulin variable heavy chain gene consensus probes with conjugated 3' minor groove binder groups for monitaring minimal residual disease childhood acute lymphoblastic leukaemia2003
Author(s)
Uchiyama M, Maesawa C, Yashima A, Itabashi T, Satoh T, Tarusawa M, Endo M, Takahashi Y, Sasaki S, Tsuchiya S, Ishida Y, Masuda T.
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Journal Title
J Clin Pathol. Dec:56(12)
Pages: 952-5
Description
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Related Report
-
[Journal Article] Japan Clinical Oncology Group. Surgery plus chemotherapy compared with surgery alone for localized squamous cell carcinoma of the thoracic esophagus : a Japan Clinical Oncology Group Study-JCOG9204.2003
Author(s)
Ando N, Iizuka T, Ide H, Ishida K, Shinoda M, Nishimaki T, Takiyama W, Watanabe H, Isono K, Aoyama N, Makuuchi H, Tanaka O, Yamana H, Ikeuchi S, Kabuto T, Nagai K, Shimada Y, Kinjo Y, Fukuda H.
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Journal Title
J Clin Oncol. Dec 15:21(24)
Pages: 4592-6
Description
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Related Report
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[Publications] Uchiyama M, Maesawa C, Yashima A, Tarusawa M, Satoh T, Ishida Y, Ito S, Murai K, Enomoto S, Utsugisawa T, Masuda T: "Short consensus probes with 3'-minor groove binder of the immunoglobulin heavy-chain gene for real-time quantitative PCR in B-cell non-Hodgkin lymphomas."Lab Invest. 84(in press). (2004)
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[Publications] Akiyama Y, Maesawa C, Wada K, Fujisawa K, Itabashi T, Noda Y, Honda T, Sato N, Ishida K, Takagane A, Saito K, Masuda T.: "Human PinX1, a potent telomerase inhibitor, is not involved in human gastrointestinal tract carcinoma."Oncol Rep. 11・4. 871-874 (2004)
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[Publications] Ogasawara S, Maesawa C, Yamamoto M, Akiyama Y, Wada K, Fujisawa K, Higuchi T, Tomisawa Y, Sato N, Endo S, Saito K, Masuda T: "Disruption of cell-type-specific methylation of the Maspin gene promoter is frequently involved in undifferentiated thyroid cancers."Oncogene. 23・5. 1117-1124 (2004)
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