Regulatory mechanism for cancer stem cells in various tumors

• Project/Area Number: 23590425
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Osaka University
• Principal Investigator: EIICHI Morii 大阪大学, 医学(系)研究科(研究院), 教授 (10283772)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 腫瘍幹細胞 / 制御因子 / 腫瘍 / 子宮内膜癌 / リンパ腫 / 病理学 / マーカー / 発現調節機構

Research Abstract

Cancer stem cells (CSCs) are supposed to cause metastasis and recurrence of tumors, because these are restant to various therapies. Here, we analyzed CSCs in various tumors. In Hodgkin lymphoma, small cells with single nucleus were CSCs, which expeled efficiently reactive oxygen species (ROS). In lymphoplasmacytic lymphoma, tumor cells with no expression of B lymphocyte and plasma cell markers were CSCs, because these non-expressing cells yielded B lymphocyte marker-positive and plasma cell marker-positive cells. These non-expressing cells were resistant to anti-cancer drugs and eliminated ROS. Moreover, in endometrioid adenocarcinoma, aldehyde dehydrogenase (ALDH) high cells, which were revealed to be CSCs, were regulated by TGF-beta signal. The inhibition of signal increased ALDH-hi population, and the addition of TGF-beta stimulator reduced ALDH-hi. These results suggested that CSCs were present in various tumors, and their regulation will be necessary for anti-tumor therapies.

Research Products

• [Journal Article] Characterization of subpopulation lacking B cell and plasma cell markers in Waldenstrom macroglobulinemia cell line (2014)
  • Author(s): Wada N, Zhan M, Hori Y, Honma K, Ikeda JI, Morii E
  • Journal Title: Lab Invest Volume: 94 Pages: 79-88
  • Peer Reviewed
• [Journal Article] Characterization of subpopulation lacking both B-cell and plasma cell markers in Waldenstrom macroglobulinemia cell line. (2014)
  • Author(s): Wada N, Zhan M, Hori Y, Honma K, Ikeda J, Morii E.
  • Journal Title: Lab Invest. Volume: 94 Issue: 1 Pages: 79-88
  • DOI: 10.1038/labinvest.2013.129
  • Peer Reviewed
• [Journal Article] Critical role of Trib1 in differentiation of tissue-resident M2-like macrophages (2013)
  • Author(s): Satoh S, Kidoya H, Naito H, Yamamoto M, Takemura N, Nakagawa K, Yoshioka Y, Morii E, Takakura N, Takeuchi O,Akira S
  • Journal Title: Nature Volume: 495 Pages: 524-528
• [Journal Article] Expression of FoxO3a in clinical cases of malignant lymphoma (2013)
  • Author(s): Ikeda JI, Tian T, Wang Y, Hori Y, Honma K, Wada N, Morii E
  • Journal Title: Pathol Res Pract Volume: 209 Pages: 716-720
  • Peer Reviewed
• [Journal Article] Inhibitory effect of Nodal on the expression of aldehyde dehydrogenase 1 in endometrioid adenocarcinoma of uterus (2013)
  • Author(s): Wang Y, Jiang Y, Tian T, Hori Y, Wada N, Ikeda JI, Morii E
  • Journal Title: Biochem Biophys Res Comm Volume: 440 Pages: 731-736
  • Peer Reviewed
• [Journal Article] 腫瘍における多様な形態病理と臨床 (2013)
  • Author(s): 森井英一
  • Volume: 31
  • Pages: 1252-1254
• [Journal Article] Inhibitory effect of Nodal on the expression of aldehyde dehydrogenase 1 in endometrioid adenocarcinoma of uterus. (2013)
  • Author(s): Wang Y, Jiang Y, Tian T, Hori Y, Wada N, Ikeda J, Morii E.
  • Journal Title: Biochem Biophys Res Commun. Volume: 440 Issue: 4 Pages: 731-736
  • DOI: 10.1016/j.bbrc.2013.09.139
  • Peer Reviewed
• [Journal Article] Expression of FoxO3a in clinical cases of malignant lymphoma. (2013)
  • Author(s): Ikeda J, Tian T, Wang Y, Hori Y, Honma K, Wada N, Morii E.
  • Journal Title: Pathol Res Pract. Volume: 209 Issue: 11 Pages: 716-720
  • DOI: 10.1016/j.prp.2013.08.003
  • Peer Reviewed
• [Journal Article] A point mutation in Semaphorin 4A associates with defective endosomal sorting and causes retinal degeneration (2013)
  • Author(s): Nojima S, et al.
  • Journal Title: Nat Commun Volume: 4 Issue: 1 Pages: 1406-1406
  • DOI: 10.1038/ncomms2420
  • Peer Reviewed
• [Journal Article] Echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangement in congenital pulmonary airway malformation. (2013)
  • Author(s): Tetsumoto S, Kijima T, Morii E, Goya S, Minami T, Hirata H, Takahashi R, Kohmo S, Inoue K, Nagatomo I, Takeda Y, Kida H, Tachibana I, Kumanogoh A.
  • Journal Title: Clin Lung Cancer. Volume: 14 Issue: 4 Pages: 457-460
  • DOI: 10.1016/j.cllc.2012.12.005
  • Peer Reviewed
• [Journal Article] MiR-424/503-mediated Rictor upregulation promotes tumor progression (2013)
  • Author(s): Oneyama C, Kito Y, Asai R, Ikeda J, Yoshida T, Okuzaki D, Kokuda R, Kakumoto K, Takayama K, Inoue S, Morii E, Okada M.
  • Journal Title: PLos ONE 2013 Volume: 8(11) Issue: 11 Pages: e80300-e80300
  • DOI: 10.1371/journal.pone.0080300
  • Peer Reviewed
• [Journal Article] Pulmonary fibroblasts induce epithelial mesenchymal transition and some characteristics of stem cells in non-small cell lung cancer. (2013)
  • Author(s): Shintani Y, Abulaiti A, Kimura T, Funaki S, Nakagiri T, Inoue M, Sawabata N, Minami M, Morii E, Okumura M.
  • Journal Title: Ann Thorac Surg. Volume: 96 Issue: 2 Pages: 425-433
  • DOI: 10.1016/j.athoracsur.2013.03.092
  • Peer Reviewed
• [Journal Article] Critical role of Trib1 for the differentiation of adipose tissue-resident macrophages maintaining metabolic homeostasis. (2013)
  • Author(s): Satoh T, Kidoya H, Naito H, Yamamoto M, Takemura N, Nakagawa K, Yoshioka Y, Morii E, Takakura N, Takeuchi O, Akira S
  • Journal Title: Nature Volume: 495(7442) Issue: 7442 Pages: 524-528
  • DOI: 10.1038/nature11930
  • Peer Reviewed
• [Journal Article] IL-6 amplifier activation in epithelial regions of bronchi after allogeneic lung transplantation. (2013)
  • Author(s): Lee J, Nakagiri T
  • Journal Title: International Immunology Volume: 2 Issue: 5 Pages: 319-332
  • DOI: 10.1093/intimm/dxs158
  • Peer Reviewed
• [Journal Article] Prognostic significance of elongator protein 3 (ELP3) expression in endometrioid adenocarcinoma (2012)
  • Author(s): Wang Y, Ikeda JI, Rahadiani N, Mamat S, Ueda Y, Tian T, Enomoto T, Kimura T, Aozasa K, Morii E
  • Journal Title: Oncol Let Volume: 3 Pages: 25-29
  • Peer Reviewed
• [Journal Article] Tumor-associated macrophages in diffuse large B-cell lymphoma : a study of the Osaka Lymphoma Study Group (2012)
  • Author(s): Wada N, Zaki MA, Hori Y, Hashimoto K, Tsukaguchi M, Tatsumi Y, Ishikawa J, Tominaga N, Sakoda H, Take H, Tsudo M, Kuwayama M, Morii E, Aozasa K
  • Journal Title: Histopathology Volume: 60 Pages: 313-319
  • Peer Reviewed
• [Journal Article] Reactive oxygen species and aldehyde dehydrogenase activity in Hodgkin lymphoma cells (2012)
  • Author(s): Ikeda JI, Mamat S, Tian T, Wang Y, Luo W, Rahadiani N, Aozasa K, Morii E
  • Journal Title: Lab Invest Volume: 92 Pages: 606-614
  • Peer Reviewed
• [Journal Article] Role of leucine-rich pentatricopeptide repeat motif-containing protein (LRPPRC) for anti-apoptosis and tumorigenesis in cancers (2012)
  • Author(s): Tian T, Ikeda JI, Wang Y, Mamat S, Luo W, Aozasa K, Morii E
  • Journal Title: Eur J Cancer Volume: 48 Pages: 2462-2473
  • Peer Reviewed
• [Journal Article] Diffuse large B cell lymphoma with an interfollicular pattern of proliferation shows a favorable prognosis : a study of the Osaka Lymphoma Study Group (2012)
  • Author(s): Wada N, Zaki MA, Kohara M, Ogawa H, Sugiyama H, Nomura S, Matsumura I, Hino M, Kanakura Y, Inagaki H, Morii E, Aozasa K
  • Journal Title: Histopathology Volume: 60 Pages: 924-932
  • Peer Reviewed
• [Journal Article] Expression level of pre-B-cell leukemia transcription factor 2 (PBX2) as a prognostic marker for gingival squamous cell carcinoma (2012)
  • Author(s): Qiu Y, Wang ZL, Jin SQ, Pu YF, Toyosawa S, Aozasa K, Morii E
  • Journal Title: J Zhenjiang Univ Sci B Volume: 13 Pages: 168-175
  • Peer Reviewed
• [Journal Article] Inhibitory effect of PPARg on NR0B1 in tumorigenesis of lung adenocarcinoma (2012)
  • Author(s): Susaki Y, Inoue M, Minami M, Sawabata N, Shintani Y, Nakagiri T, Funaki S, Aozasa K, Okumura M, Morii E
  • Journal Title: Int J Oncol Volume: 41 Pages: 1278-1284
  • Peer Reviewed
• [Journal Article] 病理組織における腫瘍幹細胞の可視化を目指して生産と技術 (2012)
  • Author(s): 森井英一
  • Volume: 64
  • Pages: 85-89
• [Journal Article] Role of leucine-rich pentatricopeptide repeat motif-containing protein (LRPPRC) for anti-apoptosis and tumorigenesis in cancers. (2012)
  • Author(s): Tian T, Ikeda JI, Wang Y, Mamat S, Luo W, Aozasa K and Morii E.
  • Journal Title: Eur J Cancer Volume: 48 Issue: 15 Pages: 2462-2473
  • DOI: 10.1016/j.ejca.2012.01.018
  • Peer Reviewed
• [Journal Article] Reactive oxygen species and aldehyde dehydrogenase activity in Hodgkin lymphoma cells. (2012)
  • Author(s): Ikeda J, Mamat S, Tian T, Wang Y, Luo W, Rahadiani N, Aozasa K, Morii E.
  • Journal Title: Lab Invest. Volume: 92 Issue: 4 Pages: 606-614
  • DOI: 10.1038/labinvest.2012.4
  • Peer Reviewed
• [Journal Article] MicroRNA-mediated upregulation of integrin-linked kinase promotes Src-induced tumor progression. (2012)
  • Author(s): Oneyama C, Morii E, Okuzaki D, Takahashi Y, Ikeda J, Wakabayashi N, Akamatsu H, Tsujimoto M, Nishida T, Aozasa K, Okada M.
  • Journal Title: Oncogene. Volume: 31 Pages: 1623-35
  • Peer Reviewed
• [Journal Article] Tumour-associated macrophages in diffuse large B-cell lymphoma: a study of the Osaka Lymphoma Study Group. (2012)
  • Author(s): Wada N, Zaki MA, Hori Y, Hashimoto K, Tsukaguchi M, Tatsumi Y, Ishikawa J, Tominaga N, Sakoda H, Take H, Tsudo M, Kuwayama M, Morii E, Aozasa K; Osaka Lymphoma Study Group.
  • Journal Title: Histopathology. Volume: 60 Pages: 313-9
  • Peer Reviewed
• [Journal Article] Expression of aldehyde dehydrogenase 1 (ALDH1) in endometrioid adenocarcinoma and its clinical implications (2011)
  • Author(s): Rahadiani N, Ikeda JI, Mamat S, Matsuzaki S, Ueda Y, Umehara R, Tian T, Wang Y, Enomoto T, Kimura T, Aozasa K, Morii E
  • Journal Title: Cancer Sci Volume: 102 Pages: 903-908
  • NAID: 10029292931
  • Peer Reviewed
• [Journal Article] Presence of B-cell clones in T-cell lymphoma (2011)
  • Author(s): Zaki MA, Wada N, Kohara M, Ikeda JI, Hori Y, Fujita S, Ogawa H, Sugiyama H, Hino M, Kanakura Y, Morii E, Aozasa K
  • Journal Title: Eur J Haematol Volume: 86 Pages: 412-419
  • Peer Reviewed
• [Journal Article] Pretreatment of leukocytosis is an indicator of poor prognosis in patients with cervical cancer (2011)
  • Author(s): Mabuchi S, Matsumoto Y, Isohashi F, Yoshioka Y, Ohashi H, Morii E, Hamasaki T, Aozasa K, Mutch DG, Kimura T
  • Journal Title: Gynecol Oncol Volume: 122 Pages: 25-32
  • Peer Reviewed
• [Journal Article] Prognostic implication of types of tumor-associated macrophages in Hodgkin lymphoma (2011)
  • Author(s): Zaki MA, Wada N, Ikeda JI, Shibayama H, Hashimoto K, Yamagami T, Tatsumi Y, Tsukaguchi M, Take H, Tsudo M, Morii E, Aozasa K
  • Journal Title: Virchows Arch Volume: 459 Pages: 361-366
  • Peer Reviewed
• [Journal Article] Significance of aldehyde dehydrogenase 1 expression in stromal cells of diffuse large B-cell lymphoma (2011)
  • Author(s): Fujita S, Morii E, Rahadiani N, Wada N, Hori Y, Ikeda JI, Aozasa K
  • Journal Title: Exp Therap Med Volume: 2 Pages: 591-594
  • Peer Reviewed
• [Journal Article] Transcriptional regulation of aldehyde dehydrogenase 1A1 gene by alternative spliced forms of nuclear factor Y in tumorigenic population of endometrial adenocarcinoma (2011)
  • Author(s): Mamat S, Ikeda JI, Tian T, Wang Y, Luo W, Aozasa K, Morii E
  • Journal Title: Genes Cancer Volume: 2 Pages: 979-984
  • Peer Reviewed
• [Journal Article] がん幹細胞の動態顕微鏡 (2011)
  • Author(s): 森井英一
  • Volume: 46
  • Pages: 84-84
• [Journal Article] 腫瘍幹細胞マーカー顕微鏡 (2011)
  • Author(s): 森井英一, 池田純一郎
  • Volume: 46
  • Pages: 85-88
• [Journal Article] 腫瘍幹細胞の可視化を目指してクリニシアン (2011)
  • Author(s): 森井英一
  • Volume: 58
  • Pages: 1393-1398
• [Journal Article] Expression of aldehyde dehydrogenase 1 (ALDH1) in endometrioid adenocarcinoma and its clinical implications. (2011)
  • Author(s): Rahadiani N, Ikeda J, Mamat S, Matsuzaki S, Ueda Y, Umehara R, Tian T, Wang Y, Enomoto T, Kimura T, Aozasa K, Morii E.
  • Journal Title: Cancer Sci. Volume: 102 Pages: 903-8
  • NAID: 10029292931
  • Peer Reviewed
• [Journal Article] Prognostic value of endoscopic biopsy findings after induction chemoradiotherapy with and without surgery for esophageal cancer. (2011)
  • Author(s): Miyata H, Yamasaki M, Takiguchi S, Nakajima K, Fujiwara Y, Konishi K, Morii E, Mori M, Doki Y.
  • Journal Title: Ann Surg. Volume: 253 Pages: 279-84
  • Peer Reviewed
• [Journal Article] Presence of B-cell clones in T-cell lymphoma (2011)
  • Author(s): Zaki MA, Wada N, Kanakura Y, et al
  • Journal Title: Eur J Haematol Volume: 86 Issue: 5 Pages: 412-419
  • DOI: 10.1111/j.1600-0609.2011.01597.x
  • Peer Reviewed
• [Journal Article] MicroRNA-mediated downregulation of mTOR/FGFR3 controls tumor growth induced by Src-related oncogenic pathways. (2011)
  • Author(s): Oneyama C, Ikeda J, Okuzaki D, Suzuki K, Kanou T, Shintani Y, Morii E, Okumura M, Aozasa K, Okada M.
  • Journal Title: Oncogene. Volume: 30 Pages: 3489-501
  • Peer Reviewed
• [Journal Article] Pretreatment leukocytosis is an indicator of poor prognosis in patients with cervical cancer. (2011)
  • Author(s): Mabuchi S, Matsumoto Y, Isohashi F, Yoshioka Y, Ohashi H, Morii E, Hamasaki T, Aozasa K, Mutch DG, Kimura T.
  • Journal Title: Gynecol Oncol. Volume: 122 Pages: 25-32
  • Peer Reviewed
• [Journal Article] The prevalence of human papillomavirus in oral premalignant lesions and squamous cell carcinoma in comparison to cervical lesions used as a positive control. (2011)
  • Author(s): Ishibashi M, Kishino M, Sato S, Morii E, Ogawa Y, Aozasa K, Kogo M, Toyosawa S.
  • Journal Title: Int J Clin Oncol. Volume: 16 Pages: 646-53
  • NAID: 10030247285
  • Peer Reviewed
• [Journal Article] Prognostic implication of types of tumor-associated macrophages in Hodgkin lymphoma. (2011)
  • Author(s): Zaki MA, Wada N, Ikeda J, Shibayama H, Hashimoto K, Yamagami T, Tatsumi Y, Tsukaguchi M, Take H, Tsudo M, Morii E, Aozasa K.
  • Journal Title: Virchows Arch. Volume: 459 Pages: 361-6
  • Peer Reviewed
• [Journal Article] Metastatic mucinous adenocarcinoma of the ovary is characterized by advanced patient age, small tumor size, and elevated serum CA125. (2011)
  • Author(s): Maeda-Taniguchi M, Ueda Y, Miyake T, Miyatake T, Kimura T, Yoshino K, Fujita M, Wakasa T, Ohashi H, Morii E, Enomoto T, Kimura T.
  • Journal Title: Gynecol Obstet Invest. Volume: 72 Pages: 196-202
  • Peer Reviewed
• [Presentation] 医療イノベーションの案内人・病理学ー臨床・基礎研究で病理学が担うもの (2013)
  • Organizer: 第5回プラズマフォーラム特別講演
  • Place of Presentation: 産業総合技術研究所(東京)
  • Year and Date: 2013-12-26
• [Presentation] 腫瘍幹細胞の可視化とその問題点 (2013)
  • Organizer: 第52回日本臨床細胞学会秋期大会要望講演
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2013-11-02
• [Presentation] アルデヒド脱水素酵素の腫瘍幹細胞における発現調節機構 (2013)
  • Organizer: 第52回日本臨床細胞学会秋期大会ワークショップ
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2013-11-02
• [Presentation] 腫瘍幹細胞の動態ー病理の立場から (2013)
  • Organizer: 第64回はびきのオンコロジー研究会
  • Place of Presentation: 大阪府呼吸器アレルギー総合医療センター(大阪)
  • Year and Date: 2013-10-11
• [Presentation] Invasive ability of cancer initiating cells in endometrioid adenocarcinoma (2013)
  • Organizer: 第72回日本癌学会総会シンポジウム
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 2013-10-04
• [Presentation] 癌幹細胞に組織から迫ってみる (2013)
  • Organizer: 54回日本組織細胞化学会総会ワークショップ
  • Place of Presentation: 航空会館(東京)
  • Year and Date: 2013-09-28
• [Presentation] がん幹細胞の制御因子ーアルデヒド脱水素酵素の視点より (2013)
  • Organizer: 第102回日本病理学会総会シンポジウム
  • Place of Presentation: ロイトン札幌(札幌)
  • Year and Date: 2013-06-07
• [Presentation] アルデヒド脱水素酵素の腫瘍幹細胞における発現調節機構 (2013)
  • Author(s): 森井英一
  • Organizer: 第５２回日本臨床細胞学会秋期大会
  • Place of Presentation: 大阪国際会議場
  • Invited
• [Presentation] 腫瘍幹細胞の可視化とその問題点 (2013)
  • Author(s): 森井英一
  • Organizer: 第５２回日本臨床細胞学会秋期大会
  • Place of Presentation: 大阪国際会議場
  • Invited
• [Presentation] 腫瘍幹細胞の動態ー病理の立場から (2013)
  • Author(s): 森井英一
  • Organizer: 第６４回はびきのオンコロジー研究会
  • Place of Presentation: 大阪府呼吸器アレルギー総合医療センター
  • Invited
• [Presentation] Invasive ability of cancer initiating cells in endometrioid adenocarcinoma (2013)
  • Author(s): 森井英一
  • Organizer: 第７２回日本癌学会総会
  • Place of Presentation: パシフィコ横浜
  • Invited
• [Presentation] 癌幹細胞に組織から迫ってみる (2013)
  • Author(s): 森井英一
  • Organizer: 第５４回日本組織細胞化学会総会
  • Place of Presentation: 航空会館
  • Invited
• [Presentation] がん幹細胞の制御因子ーアルデヒド脱水素酵素の視点より (2013)
  • Author(s): 森井英一
  • Organizer: 第１０２回日本病理学会総会
  • Place of Presentation: ロイトン札幌
  • Invited
• [Presentation] 腫瘍幹細胞の可視化を目指してーアルデヒド脱水素酵素を中心に (2012)
  • Organizer: 第40回和歌山悪性腫瘍研究会特別講演
  • Place of Presentation: 和歌山ビッグ愛大ホール(和歌山)
  • Year and Date: 2012-12-15
• [Presentation] 病理組織における腫瘍幹細胞の可視化を目指して (2012)
  • Organizer: 第32回日本小児病理研究会
  • Place of Presentation: 大阪市総合医療センターさくらホール(大阪)
  • Year and Date: 2012-09-08
• [Presentation] 腫瘍幹細胞の可視化を目指してーアルデヒド脱水素酵素を中心に (2012)
  • Author(s): 森井英一
  • Organizer: 和歌山悪性腫瘍研究会
  • Place of Presentation: 和歌山ビッグ愛ホール
  • Invited
• [Presentation] 病理組織における腫瘍幹細胞の可視化を目指して (2012)
  • Author(s): 森井英一
  • Organizer: 小児病理学会
  • Place of Presentation: 大阪市立総合医療センター
  • Invited
• [Presentation] アルデヒド脱水素酵素を利用した子宮内膜癌における腫瘍幹細胞の検討 (2012)
  • Author(s): 森井英一
  • Organizer: 日本サイトメトリー学会
  • Place of Presentation: 千里ライフサイエンスセンター
  • Invited
• [Presentation] 癌幹細胞 (2012)
  • Author(s): 森井英一
  • Organizer: 日本病理学会
  • Place of Presentation: 京王プラザホテル
  • Invited
• [Presentation] 子宮内膜癌におけるALDH発現の意義 (2011)
  • Author(s): 森井英一
  • Organizer: 第７０回日本癌学会総会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] 腫瘍幹細胞と浸潤、転移 (2011)
  • Author(s): 森井英一
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] 血管腫・血管奇形の病理診断 (2011)
  • Author(s): 森井英一
  • Organizer: 第１９回つきじ放射線研究会(招待講演)
  • Place of Presentation: 聖路加国際病院
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/molpath/index.html