Clinical application of the minimal residual disease monitoring in canine lymphoma

• Project/Area Number: 23380182
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Clinical veterinary science
• Research Institution: The University of Tokyo
• Principal Investigator: TSUJIMOTO Hajime 東京大学, 農学生命科学研究科, 教授 (60163804)
• Co-Investigator(Kenkyū-buntansha): OHNO Koichi 東京大学, 大学院・農学生命科学研究科, 准教授 (90294660) ; FUJINO Yasuhito 東京大学, 大学院・農学生命科学研究科, 助教 (70401180)
• Co-Investigator(Renkei-kenkyūsha): NISHIMURA Ryohei 東京大学, 大学院・農学生命科学研究科, 教授 (80172708) ; UCHIDA Kazuyuki 東京大学, 大学院・農学生命科学研究科, 准教授 (10223554)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000); Fiscal Year 2013: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2011: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
• Keywords: 動物 / 犬 / リンパ腫 / 微小残存病変 / 化学療法 / 予後

Research Abstract

Overall survival durations after standard chemotherapies have been reported as long as 1 year. In the present study, we assessed the efficacy of the chemotherapeutic protocols objectively by quantification of the minimal residual disease, MRD, after chemotherapy with real-time PCR. Through the results of MRD monitoring, we could propose several strategies to improve the chemotherapeutic protocols such as dose change of the drugs, requirement of the consolidation chemotherapy, and the necessity of the early re-induction chemotherapy during complete remission. The present studies were conceivably very helpful to improve the chemotherapeutic modalities for canine lymphoma as well as indicative of the usefulness of canine lymphoma as an animal model for human non-Hodgkin lymphoma.

Research Products

• [Journal Article] Prognostic significance of the expression levels of the p16, p15, and p14genes in dogs with high-grade lymphoma (2014)
  • Author(s): Fujiwara-Igarashi A, Goto-Koshino Y, Sato M, Maeda S, Igarashi H, Takahashi M, Fujino Y, Ohno K, Tsujimoto H.
  • Journal Title: Vet J Volume: 199(2) Issue: 2 Pages: 236-244
  • DOI: 10.1016/j.tvjl.2013.11.004
  • Peer Reviewed
• [Journal Article] Epigenetic regulation of the ABCBl gene in drug-sensitive and drug-resistant lymphoid tumour cell lines obtained from canine patients (2014)
  • Author(s): Tomiyasu H, Goto-Koshino Y, Fujino Y, Ohno K, Tsujimoto H.
  • Journal Title: Vet J Volume: 199(1) Issue: 1 Pages: 103-109
  • DOI: 10.1016/j.tvjl.2013.10.022
  • Peer Reviewed
• [Journal Article] Antitumour effect and modulation of expression of ABCB1 gene by perifosine in canine lymphoid tumour cell lines. (2014)
  • Author(s): Tomiyasu, H., Goto-Koshino, Y., Fujino, Y., Ohno, K. and Tsujimoto, H.
  • Journal Title: The Veterinary Journal Volume: 201 Issue: 1 Pages: 83-90
  • DOI: 10.1016/j.tvjl.2014.04.002
  • Peer Reviewed
• [Journal Article] Inhibition of p16 tumor suppressor gene expression via promoter hypermethylation in canine lymphoid tumor cells. (2014)
  • Author(s): Fujiwara-Igarashi, A., Goto-Koshino, Y., Mochizuki, H., Sato, M., Fujino, Y., Ohno, K. and Tsujimoto, H.
  • Journal Title: Research in Veterinary Science Volume: 97 Issue: 1 Pages: 60-63
  • DOI: 10.1016/j.rvsc.2014.04.008
  • Peer Reviewed
• [Journal Article] Establishment of Five Canine Lymphoma Cell Lines and Tumor Formation in a Xenotransplantation Model (2013)
  • Author(s): Umeki, S., Ema, Y., Suzuki, R., Kubo, M., Hayashi, T., Okamura, Y., Yamazaki, J., Tsujimoto, H., Tani, K., Hiraoka, H., Okuda, M. and Mizuno, T
  • Journal Title: Journal of Veterinary Medical Science Volume: 75 Issue: 4 Pages: 467-474
  • DOI: 10.1292/jvms.12-0448
  • NAID: 130002502194
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed
• [Journal Article] The prognostic significance of minimal residual disease in the early phases of chemotherapy in dogs with high-grade B-cell lymphoma (2013)
  • Author(s): Sato, M., Yamazaki, J., Goto-Koshino, Y., Takahashi, M., Fujino, Y., Ohno, K. and Tsujimoto, H
  • Journal Title: Vet. J Volume: 195 Issue: 3 Pages: 319-324
  • DOI: 10.1016/j.tvjl.2012.07.013
  • Peer Reviewed
• [Journal Article] Establishment of five canine lymphoma cell lines and tumor formation in a xenotransplantation model. (2013)
  • Author(s): Umeki, S., Ema, Y., Suzuki, R., Kubo, M., Hayashi, T., Okamura, Y., Yamazaki, J., Tsujimoto, H., Tani, K., Hiraoka, H., Okuda, M. and Mizuno, T.
  • Journal Title: Journal of Veterinary Medical Science Volume: 75
  • NAID: 130002502194
  • Peer Reviewed
• [Journal Article] Analyses on Activation of NF-κB and Effect of Bortezomib in Canine Neoplastic Lymphoid Cell Lines (2013)
  • Author(s): Kojima K, Fujino Y, Goto-Koshino Y, Ohno K, Tsujimoto H.
  • Journal Title: Journal of Veterinary Medical Science Volume: 75 Issue: 6 Pages: 727-731
  • DOI: 10.1292/jvms.12-0168
  • NAID: 130003362111
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed
• [Journal Article] Simultaneous Inactivation of the <i>p16, p15</i> and <i>p14</i> Genes Encoding Cyclin-Dependent Kinase Inhibitors in Canine T-Lymphoid Tumor Cells (2013)
  • Author(s): Fujiwara-Igarashi A, Goto-Koshino Y, Mochizuki H, Maeda S, Fujino Y, Ohno K, Tsujimoto H.
  • Journal Title: Journal of Veterinary Medical Science Volume: 75 Issue: 6 Pages: 733-742
  • DOI: 10.1292/jvms.12-0351
  • NAID: 130003362118
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed
• [Journal Article] Evaluation of the prognostic significance of BCL6 gene expression in canine high-grade B-cell lymphoma (2012)
  • Author(s): Sato M
  • Journal Title: Vet J Volume: 191 Issue: 1 Pages: 108-114
  • DOI: 10.1016/j.tvjl.2010.12.006
  • Peer Reviewed
• [Journal Article] Regulation of the expression of ABCB1 and LRP genes by MAPK/ERK pathway and its role in the generation of side population cells in canine lymphoma cell lines. (2012)
  • Author(s): Tomiyasu H, Watanabe M, Goto-Koshino Y, Fujino Y, Ohno K, Sugano S, Tsujimoto H.
  • Journal Title: Leuk Lymphoma Volume: (Epub ahead of print) Issue: 6 Pages: 1309-1315
  • DOI: 10.3109/10428194.2012.751529
  • Peer Reviewed
• [Journal Article] Increase in minimal residual disease (MRD) in peripheral blood before clinical relapse in dogs with lymphoma that achieved complete remission after chemotherapy (2011)
  • Author(s): Sato, M., Yamazaki, J., Goto-Koshino, Y., Takahashi, M., Fujino, Y., Ohno, K. and Tsujimoto, H
  • Journal Title: J. Vet. Intern. Med Volume: 25 Issue: 2 Pages: 292-296
  • DOI: 10.1111/j.1939-1676.2010.0675.x
• [Journal Article] Evaluation of of cytoreductive efficacy of vincristine, cyclophosphamide, and doxorubicin in dogs with lymphoma by measuring the number of neoplastic lymphoid cells with real-time polymerase chain reaction (2011)
  • Author(s): Sato, M., Yamazaki, J., Goto-Koshino, Y., Takahashi, M., Fujino, Y., Ohno, K. and Tsujimoto, H
  • Journal Title: J. Vet. Intern. Med Volume: 25 Issue: 2 Pages: 285-291
  • DOI: 10.1111/j.1939-1676.2011.0686.x
• [Journal Article] Characterization of canine BCL6 cDNA and detection systems for its expression (2011)
  • Author(s): Sato, M., Goto-Koshino, Y., Kanemoto, H., Mochizuki, H., Fujino, Y., Ohno, K., Tsujimoto, H.
  • Journal Title: Vet.Immunol.Immunopathol. Volume: 140 Issue: 1-2 Pages: 166-169
  • DOI: 10.1016/j.vetimm.2010.08.009
  • Peer Reviewed
• [Presentation] 犬の辺縁帯リンパ腫(marginal zone lymphoma)9頭における臨床的・臨床病理学的特徴 (2014)
  • Author(s): 水田賢司, 高橋雅, 藤野泰人, 日吉沙綾, 福島建次郎, 金本英之, 大野耕一, 坪井誠也, 内田和幸, 辻本元
  • Organizer: 第10回日本獣医がん学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-01-25
• [Presentation] 犬の辺縁帯リンパ腫(marginal zone lymphoma) 9頭における臨床的・臨床病理学的特徴 (2014)
  • Author(s): 水田賢司, 高橋雅, 藤野泰人, 日吉沙綾, 福島建次郎, 金本英之, 大野耕一, 坪井誠也, 内田和幸, 辻本元
  • Organizer: 第10回日本獣医がん学会
  • Place of Presentation: 大阪
• [Presentation] GeneScanning analysis of antigen receptor gene rearrangement in the intestinal endoscopeic biopsy specimens and its application to the diagnosis of small cell lymphoma in dogs (2013)
  • Author(s): Hiyoshi, S., Uchida, K., Nakashima, K., Fukushima, K., Kanemoto, H., Goto, Y., Fujino, Y., Ohno, K. and Tsujimoto, H
  • Organizer: The Asian Meeting of Animal Medicine Specialties (AMAMS) 2013
  • Place of Presentation: ボゴール, インドネシア
  • Year and Date: 2013-12-14
• [Presentation] 犬のリンパ腫におけるGeneScanningを用いた微小残存病変検出に関する研究 (2013)
  • Author(s): 日吉沙綾, 後藤裕子, 佐藤雅彦, 高橋雅, 藤野泰人, 大野耕一, 辻本元
  • Organizer: 第9回日本獣医内科学アカデミー学術大会
  • Place of Presentation: 横浜
  • Year and Date: 2013-02-23
• [Presentation] 犬のT-zoneリンパ腫16例における臨床的・臨床病理学的特徴 (2013)
  • Author(s): 水谷格之, 後藤裕子, 内田和幸, 高橋雅, 藤野泰人, 大野耕一, 辻本元
  • Organizer: 第9回日本獣医内科学アカデミー学術大会
  • Place of Presentation: 横浜
  • Year and Date: 2013-02-23
• [Presentation] GeneScanning analysis of antigen receptor gene rearrangement in the intestinal endoscopic biopsy specimens and its application to the diagnosis of small cell lymphoma in dogs (2013)
  • Author(s): S. Hiyoshi, K. Uchida, K. Nakashima, K. Fukushima, H. Kanemoto, Y. Goto, Y. Fujino, K. Ohno, H. Tsujimoto
  • Organizer: The Asian Meeting of Animal Medicine Specialties (AMAMS)
  • Place of Presentation: Bogor, Indonesia
• [Presentation] 犬のリンパ腫におけるGeneScanningを用いた微小残存病変検出に関する研究 (2013)
  • Author(s): 日吉沙綾、後藤裕子、佐藤雅彦、高橋雅、藤野泰人、大野耕一、辻本元
  • Organizer: 第9回日本獣医内科学アカデミー学術大会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] 猫のリンパ腫におけるリアルタイムPCRを用いた腫瘍細胞数測定系の確立 (2013)
  • Author(s): 佐藤夏美、後藤裕子、佐藤雅彦、望月浩之、高橋雅、藤野泰人、福島建次郎、大野耕一、辻本元
  • Organizer: 第9回日本獣医内科学アカデミー学術大会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] 犬のT-zoneリンパ腫16例における臨床的・臨床病理学的特徴 (2013)
  • Author(s): 水谷格之、後藤裕子、内田和幸、高橋雅、藤野泰人、大野耕一、辻本元
  • Organizer: 第9回日本獣医内科学アカデミー学術大会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] 医学から学ぶイヌのリンパ腫治療 (2012)
  • Author(s): 辻本元
  • Organizer: 日本獣医内科学アカデミー/日本獣医臨床病理学会2011年大会
  • Place of Presentation: 横浜
  • Year and Date: 2012-02-18
  • Invited
• [Presentation] イヌのリンパ腫治療の現状 (2012)
  • Author(s): 辻本元
  • Organizer: 日本獣医内科学アカデミー/日本獣医臨床病理学会2011年大会
  • Place of Presentation: パシフィコ横浜(横浜)(招待講演)
  • Year and Date: 2012-02-18
• [Presentation] 特徴的な細胞形態を示す新しいタイプの犬のリンパ腫 -Mott cell リンパ腫- (2011)
  • Author(s): 辻本元
  • Organizer: 第13回日本臨床獣医学フォーラム年次大会
  • Place of Presentation: 東京
  • Year and Date: 2011-09-17
  • Invited
• [Presentation] 特徴的な細胞形態を示す新しいタイプの犬のリンパ腫-Mott cellリンパ腫- (2011)
  • Author(s): 辻本元
  • Organizer: 第13回日本臨床獣医学フォーラム年次大会
  • Place of Presentation: ホテル・ニューオータニ(東京)(招待講演)
  • Year and Date: 2011-09-17