統合病理学部門

仁木教授から

仁木教授から

仁木教授

あいさつ

わたくしが医学部を卒業したのは1983年ですから、いまからおよそ20数年前になります。当時と比べると、病理に対する臨床からの要望と期待は、益々増してきていると感じています。乳癌の病理診断を一例にとると、以前は極論すれば癌か癌でないかを診断すれば十分でしたが、最近では癌の核異型度スコア、ホルモン受容体あるいはHER2の免疫染色が必須であり、その結果によって治療方針が決定されています。近い将来、癌をはじめとするさまざまな疾患について、病理組織からの情報をもとに、疾患の進行度の判定、予後の予測、治療薬の選択などが行われるようになると予想しています。 研究の面では、診断技術の進歩に伴って癌の早期病変の生検・切除検体が増え、非常に早期の病変から進行性の病変までの一連の検体の解析が可能となってきました。その結果、ヒトにおける発癌の過程についてさまざまな面から考察できるようになりました。方法論的にみても、免疫染色、癌遺伝子・癌抑制遺伝子の変異解析など、ホルマリン固定標本でも検索可能なことが増えてきており、病理組織から重要な知見が得られるようになっています。またこのような病理組織からの知見に加え、細胞培養、動物実験を行うことにより、さまざまな問題に多面的にアプローチすることが可能となっています。 このように臨床医学の中の病理診断、そして病理形態学をベースにした研究は、多くの可能性を秘めているのですが、残念なことに近年病理を志す人が減少しています。現在、日本国内の病理専門医は2000人足らずであり、しかも相対的に30,40代の病理医が不足しています。私たちは、病理学と病理診断に興味をお持ちの先生方に広く門戸を開放しています。病理診断と研究の両面で若い先生方に活躍の場を提供できるものと自負しています。 ご連絡をお待ちしています。

統合病理のネーミングについて

自治医大に赴任するにあたって、部門名を考えて下さい、というお話があった。分子病理、実験病理、基礎病理などなどさまざまな名称があるが、どれも自分のもつ病理学のイメージにしっくりとしない。しばし考えたあと、現在の統合病理(英語ではIntegrative Pathology)という余り聞き慣れない名称を選んだ。ちなみにIntegrationという英語は、いろいろな部分や要素を統合、調和、集大成する、という意味がある。 現在、病理学の置かれている状況を考えると、臨床医学と基礎医学をIntegrateする、形態学と分子レベルの情報をIntegrateする、といったことが重要なのではないか。もともと病理形態学は、広い視野にたって現象全体をみわたすようなことを得意としており、生化学的な分析とはアプローチが違っていてよい。 現在は癌の研究をしているが、創傷治癒、再生、線維化、発生、老化など、他の研究分野から発信される情報にも新鮮な興味を持ち続けたいと思う。そして多岐にわたる情報をintegrateできるようでありたいと思う。

これまでの発表論文

1. Matsubara D, Kishaba Y, Ishikawa S, Sakatani T, Oguni S, Tamura T, Hoshino H, Sugiyama Y, Endo S, Murakami Y, Aburatani H, Fukayama M, Niki T. Lung Cancer with Loss of BRG1/BRM, shows Epithelial Mesenchymal Transition Phenotype and Distinct Histologic and Genetic Features. Cancer Sci 2013;104:266-273.
2. Sakuma Y, Matsukuma S, Nakamura Y, Yoshihara M, Koizume S, Sekiguchi H, Saito H, Nakayama H, Kameda Y, Yokose T, Oguni S, Niki T, Miyagi Y. Enhanced autophagy is required for survival in EGFR-independent EGFR-mutant lung adenocarcinoma cells. Lab Invest 2013:93:1137-1146.
3. Ohzawa H, Sakatani T, Niki T, Yasuda Y, Hozumi Y. Pathological responses and survival of patients with human epidermal growth factor receptor 2-positive breast cancer who received neoadjuvant chemotherapy including trastuzumab. Breast Cancer. 2013 (in press)
4. Saito S, Hosoya Y, Morishima K, Ui T, Haruta H, Kurashina K, Meguro Y, Zuiki T, Sata N, Fujii H, Matsubara D, Niki T, Lefor AT, Yasuda Y. A clinicopathological and immunohistochemical study of gastric cancer with squamous cell carcinoma components: A clinically aggressive tumor. J Dig Dis. 2012;13:407-13.
5. Matsubara D, Kanai Y, Ishikawa S, Ohara S, Yoshimoto T, Sakatani T, Oguni S, Tamura T, Kataoka H, Endo S, Murakami Y, Aburatani H, Fukayama M, Niki T. Identification of CCDC6-RET Fusion in the Human Lung Adenocarcinoma Cell Line, LC-2/ad. J Thorac Oncol. 2012;7:1872-1876.
6. Matsubara D, Niki T. Epidermal growth factor receptor mutation and chemosensitivity. J Thorac Oncol 2012;4:771-2.
7. Terasaki H, Kato S, Matsuno Y, Kusumoto M, Niki T, Hayashi A, Terasaki K, Hayabuchi N. Lung Adenocarcinoma, Mixed Subtype: Histopathologic Basis for High-Resolution Computed Tomography Findings. J Thorac Imaging 2011; 26:74-81.
8. Goto A, Li CP, Ota S, Niki T, Ohtsuki Y, Kitajima S, Yonezawa S, Koriyama C, Akiba S, Uchima H, Lin YM, Yeh KT, Koh JS, Kim CW, Kwon KY, Nga ME, Fukayama M. Human papillomavirus infection in lung and esophageal cancers: Analysis of 485 Asian cases. J Med Virol. 2011;83:1383-90.
9. Kishaba Y, Matsubara D, Niki T. Heterogenous Expression of nestin in myofibroblasts of various human tissues. Pathol Int 2010;60:378–385.
10. Sakamoto K, Sakurai S, Kanda T, Sakuma Y, Hishima T, Hironaka M, Bamba T, Keira Y, Takano Y, Niki T, Hasegawa T, Hirota S. Pleomorphic phenotypes of gastrointestinal stromal tumors at metastatic sites with or without imatinib treatment. Cancer Sci 2010;101:1270-1278.
11. Matsubara D, Ishikawa S, Oguni S, Aburatani H, Fukayama M, Niki T. Molecular predictors of sensitivity to the MET inhibitor PHA665752 in lung carcinoma cells. J Thorac Oncol 2010;5:1317-1324.
12. Matsubara D, Ishikawa S, Oguni S, Aburatani H, Fukayama M, Niki T.
Co-activation of epidermal growth factor receptor and c-MET defines a distinct subset of lung adenocarcinomas. Am J Pathol 2010;177:2191-2204.
13. Matsubara D, Morikawa T, Goto A, Nakajima J, Fukayama M, Niki T. Subepithelial myofibroblast in lung adenocarcinoma: a histologic indicator of excellent prognosis. Mod Pathol 2009;22:776-85.
14. Saito S, Hosoya Y, Zuiki T, Hyodo M, Alan Lefor, Sata N, Nagase M, Nakazawa M, Matsubara D, Niki T, Yasuda Y. A clinicopathologic study of basaloid squamous carcinoma of the esophagus. Esophagus 2009;6:177–181.
15. Zuiki T, Hosoya Y, Ui T, Haruta H, Kurashina K, Saito S, Alan Lefor, Niki T, Nakazawa M, Yasuda Y. Therapeutic effectiveness of chemoradiotherapy for carcinosarcoma of the esophagus: two case reports and a review of the literature. Esophagus 2009;6:189-95.
16. Nakamura Y, Matsubara D, Goto A, Ota S, Oguni S, Ishikawa S, Aburatani H, Miyazawa K, Fukayama M, Niki T. Constitutive activation of c-Met is correlated with c-Met overexpression and dependent on cell-matrix adhesion in lung adenocarcinoma cell lines. Cancer Sci 2008;99:14-22.
17. Inamura K, Takeuchi K, Togashi Y, Nomura K, Ninomiya H, Okui M, Satoh Y, Okumura S, Nakagawa K, Soda M, Lim CY, Niki T, Mano H, Ishikawa Y.EML4-ALK fusion is linked to histological characteristics in a subset of lung cancers. J Thorac Oncol. 2008;3:13-7.
18. Li CP, Goto A, Watanabe A, Murata K, Ota S, Niki T, Aburatani H, Fukayama M. AKR1B10 in usual interstitial pneumonia: Expression in squamous metaplasia in association with smoking and lung cancer. Pathol Res Pract. 2008;204:295-304.
19. Haruta H, Hosoya Y, Sakuma K, Shibusawa H, Satoh K, Yamamoto H, Tanaka A, Niki T, Sugano K, Yasuda Y. Clinicopathological study of lymph-node metastasis in 1,389 patients with early gastric cancer: assessment of indications for endoscopic resection. J Dig Dis. 2008;9:213-218.
20. Wang T, Niki T, Goto A, Ota S, Morikawa T, Nakamura Y, Ohara E, Ishikawa S, Aburatani H, Nakajima J, Fukayama M. Hypoxia increases the motility of lung adenocarcinoma cells A549 via activation of the epidermal growth factor receptor pathway. Cancer Sci 2007;98:506-11.
21. Nakamura Y, Niki T, Goto A, Morikawa T, Miyazawa K, Nakajima J, Fukayama M. c-Met activation in lung adenocarcinoma tissues: an immunohistochemical analysis. Cancer Sci. 2007;98:1006-13.
22. Murata K, Ota S, Niki T, Goto A, Li C-P, Ruriko UMR, Ishikawa S, Aburatani H, Kuriyama T, Fukayama M. p63 – key molecule in early phase of epithelial abnormality in idiopathic pulmonary fibrosis. Exp Mol Pathol. 2007;83:367-7.
23. Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, Fujiwara S, Watanabe H, Kurashina K, Hatanaka H, Bando M, Ohno S, Ishikawa Y, Aburatani H, Niki T, Sohara Y, Sugiyama Y, Mano H. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007;448:561-566.
24. Narahashi T, Niki T, Wang T, Goto A, Matsubara D, Funata N, Fukayama M. Cytoplasmic localization of p63 is associated with poor patient survival in lung adenocarcinoma. Histopathology. 2006;49:349-57.
25. Fukumoto S, Yamauchi N, Moriguchi H, Hippo Y, Watanabe A, Shibahara J, Taniguchi H, Ishikawa S, Ito H, Yamamoto S, Iwanari H, Hironaka M, Ishikawa Y, Niki T, Sohara Y, Kodama T, Nishimura M, Fukayama M, Dosaka-Akita H, Aburatani H. Over-expression of the aldo-keto reductase family protein AKR1B10 is highly correlated with smokers’ non-small cell lung carcinomas. Clin Cancer Res 2005;11:1776-1785.
26. Goto A, Nakajima J, Hara K, Niki T, Fukayama M. Lung adenocarcinoma associated with familial adenomatous polyposis. Clear cell carcinoma with beta-catenin accumulation accompanied by atypical adenomatous hyperplasia. Virchows Arch. 2005;446:73-77.
27. Uozaki H, Chong JM, Fujimoto E, Itoh M, Saito M, Sakuma K, Sudo M, Ushiku T, Niki T, Nagai H, Takada K, Fukayama M. Soft and hard keratin expression in Epstein-Barr-virus-associated gastric carcinoma. Anticancer Res. 2005;25:3183-3190.
28. Goto A, Niki T, Chi-Pin L, Matsubara D, Murakami Y, Funata N, Fukayama M. Loss of TSLC1 expression in lung adenocarcinoma: Relationships with histological subtypes, sex and prognostic significance. Cancer Sci. 2005;96:480-486.
29. Yamauchi N, Watanabe A, Hishinuma M, Ohashi KI, Midorikawa Y, Morishita Y, Niki T, Shibahara J, Mori M, Makuuchi M, Hippo Y, Kodama T, Iwanari H, Aburatani H, Fukayama M. The glypican 3 oncofetal protein is a promising diagnostic marker for hepatocellular carcinoma. Mod Pathol. 2005;18:1591-8.
30. Matsubara D, Niki T, Ishikawa S, Goto A, Ohara E, Yokomizo T, Heizmann CW, Aburatani H, Moriyama S, Moriyama H, Nishimura Y, Funata N, Fukayama M Differential expression of S100A2 and S100A4 in lung adenocarcinomas: clinicopathologic significance, relationship to p53, and identification of their target genes. Cancer Sci 2005;96:844-57.
31. Shibahara J, Goto A, Niki T, Tanaka M, Nakajima J, Fukayama M. Primary pulmonary paraganglioma: report of a functioning case with immunohistochemical and ultrastructural study. Am J Surg Pathol. 2004,28:825-829.
32. Goto A, Niki T, Terado Y, Fukushima J, Fukayama M. Prevalence of CD99 protein expression in pancreatic endocrine tumours (PETS). Histopathology. 2004;45:384-392.
33. Goto A, Niki T, Moriyama S, Funata N, Moriyama H, Nishimura Y, Tsuchida R, Kato JY, Fukayama M. Immunohistochemical study of Skp2 and Jab1, two key molecules in the degradation of P27, in lung adenocarcinoma. Pathol Int. 2004;54:675-681.
34. Terasaki H, Niki T, Matsuno Y, Yamada T, Maeshima A, Asamura H, Hayabuchi N, Hirohashi S. Lung adenocarcinoma with mixed bronchiolo-alveolar and invasive components: clinicopathological features, subclassification by extent of invasive foci, and immunohistochemical characterization. Am J Surg Pathol 2003;27:937-951.
35. Kitagawa H, Goto A, Minami M, Nakajima J, Niki T, Fukayama M. Sclerosing hemangioma of the lung with cystic appearance. Jpn J Clin Oncol. 2003;33:360-363.
36. Kitagawa H, Goto A, Niki T, Hironaka M, Nakajima J, Fukayama M. Lung adenocarcinoma associated with atypical adenomatous hyperplasia. A clinicopathological study with special reference to smoking and cancer multiplicity. Pathol Int. 2003,53:823-827.
37. Niki T, Kohno T, Iba S, Moriya Y, Takahashi Y, Saito M, Maeshima A, Yamada T, Matsuno Y, Fukayama M, Yokota J, Hirohashi S. Frequent co-localization of cox-2 and laminin-5 gamma2 chain at the invasive front of early-stage lung adenocarcinomas. Am J Pathol. 2002;160: 1129-1141.
38. Tomizawa Y, Kohno T, Kondo H, Otsuka A, Nishioka M, Niki T, Yamada T, Maeshima A, Yoshimura K, Saito R, Minna JD, Yokota J. Clinicopathological significance of epigenetic inactivation of RASSF1A at 3p21.3 in stage I lung adenocarcinoma. Clin Cancer Res. 2002;8:2362-2368.
39. Maeshima AM, Niki T, Maeshima A, Yamada T, Kondo H, Matsuno Y. Modified scar grade: a prognostic indicator in small peripheral lung adenocarcinoma. Cancer 2002;95:2546-2554.
40. Rombouts K, Niki T, Greenwel P, Vandermonde A, Wielant A, Hellemans K, De Bleser P, Yoshida M, Schuppan D, Rojkind M, Geerts A. Trichostatin A, a histone deacetylase inhibitor, suppresses collagen synthesis and prevents TGF-beta(1)-induced fibrogenesis in skin fibroblasts. Exp Cell Res. 2002;278:184-197.
41. Takei H, Asamura H, Maeshima A, Suzuki K, Kondo H, Niki T, Yamada T, Tsuchiya R, Matsuno Y. Large cell neuroendocrine carcinoma of the lung: A clinicopathologic study of eighty-seven cases. J Thorac Cardiovasc Surg. 2002;124: 285-292.
42. Nishioka M, Kohno T, Tani M, Yanaihara N, Tomizawa Y, Otsuka A, Sasaki S, Kobayashi K, Niki T, Maeshima A, Sekido Y, Minna JD, Sone S, Yokota J. MYO18B, a candidate tumor suppressor gene at chromosome 22q12.1, deleted, mutated, and methylated in human lung cancer. Proc Natl Acad Sci U S A. 2002;99:12269-12274.
43. Rombouts K, Niki T, Wielant A, Hellemans K, Schuppan D, Kormoss N and Geerts A. Effect of aldosterone on collagen steady state levels in primary and subcultured rat hepatic stellate cells. J Hepatol 2001; 34: 230-8
44. Geerts A, Eliasson C, Niki T, Wielant A, Vaeyens F, Pekny M. Formation of normal desmin intermediate filaments in mouse hepatic stellate cells requires vimentin. Hepatology 2001; 33: 177-188.
45. Tokunou M, Niki T, Eguchi K, Tsuda H, Yamada T, Matsuno Y, Kondo H, Saitoh Y, Imamura H, Hirohashi S. c-MET expression in myofibroblasts: role in autocrine activation and prognostic significance in lung adenocarcinoma. Am J Pathol 2001; 158: 1451-1463.
46. Niki T, Iba S, Yamada T, Matsuno Y, Enholm B, Hirohashi S. Expression of vascular endothelial growth factor receptor 3 in blood and lymphatic vessels of lung adenocarcinoma. J Pathol 2001; 193: 450-457.
47. Moriya Y, Niki T, Yamada T, Matsuno Y, Kondo H, Hirohashi S. Increased expression of laminin-5 and its prognostic significance in small-sized lung adenocarcinoma: an immunohistochemical analysis of 102 cases. Cancer 2001; 91: 1129-1141.
48. Terasaki H, Niki T, Hasegawa T, Yamada T, Suzuki, Kusumoto M, Fujimoto K, Hayabuchi N, Matsuno Y, Shimoda T. Primary synovial sarcoma of the lung: a case report confirmed by molecular detection of SYT-SSX fusion gene transcript. Jpn J Clin Oncol 2001; 31: 212-216.
49. Kitamura H, Kobayashi T, Kaneko M, Kusumoto M, Kodama T, Matsuno Y, Niki T. Pulmonary amyloidosis diagnosed by CT-guided transbronchial biopsy: a case report. Jpn J Clin Oncol. 2001; 31: 209-211.
50. Rombouts K, Niki T, Wielant A, Hellemans K, Geerts A. Trichostatin A, lead compound for development of antifibrogenic drugs. Acta Gastroenterol Belg. 2001;64:239-246.
51. Niki T, Iba S, Tokunou M, Yamada T, Matsuno Y, Hirohashi S. Expression of vascular endothelial growth factors A, B, C, and D and their relationships to lymph node status in lung adenocarcinoma. Clin Cancer Res 2000; 6: 2431-2439.
52. Manda R, Kohno T, Niki T, Yamada T, Takenoshita S, Kuwano H, Yokota J. Differential expression of the LAMB3 and LAMC2 genes between small cell and non-small cell lung carcinomas. Biochem Biophys Res Commun 2000; 275: 440-445.
53. Tokunou M, Niki T, Saitoh Y, Imamura H, Sakamoto M, Hirohashi S. Altered expression of the ERM proteins in lung adenocarcinoma. Lab Invest 2000; 80: 1643-1650.
54. Yamaguchi T, Suzuki K, Asamura H, Kondo H, Niki T, Yamada T, Tsuchiya R. Lung carcinoma with polypoid growth in the main pulmonary artery: Report of two cases. Jpn J Clin Oncol 2000; 30: 358-361.
55. Nishioka M, Kohno T, Takahashi M, Niki T, Yamada T, Sone S, Yokota J. Identification of a 428-kb homozygously deleted region disrupting the SEZ6L gene at 22q12.1 in a lung cancer cell line. Oncogene 2000; 19: 6251-6260.
56. Ono Y, Nakanishi Y, Ino Y, Niki T, Yamada T, Yoshimura K, Saikawa M, Nakajima T, Hirohashi S. Clinicopathologic significance of laminin-5 gamma2 chain expression in squamous cell carcinoma of the tongue. Immunohistochemical analysis of 67 lesions. Cancer 1999; 85: 2315-2321.
57. Niki T, Rombouts K, De Bleser PJ, De Smet K, Rogiers V, Schuppan D, Yoshida M, Gabbiani G, Geerts A. A histone deacetylase inhibitor, trichostatin A, suppresses myofibroblastic differentiation of rat hepatic stellate cells in primary culture. Hepatology 1999;29:858-867.
58. Niki T, Pekny M, Hellemans K, De Bleser PJ, Van Den Berg K, Vaeyens F, Quartier E, Schuit F, Geerts A. Class VI intermediate filament protein nestin is induced during activation of rat hepatic stellate cells. Hepatology 1999; 29: 520-527.
59. Geerts A, Niki T, Hellemans K, De Craemer D, Van Den Berg K, Lazou JM, Stange G, Van den Winkel M. Purification of rat hepatic stellate cells by side scatter-activated cell sorting. Hepatology 1998; 27:590-598.
60. Hasegawa T, Matsuno Y, Niki T, Hirohashi S, Shimoda T, Takayama J, Watanabe C, Kaneko A, Sano T, Sato M, Suzuki J. Second primary rhabdomyosarcomas in patients with bilateral retinoblastoma: a clinicopathologic and immunohistochemical study. Am J Surg Pathol 1998;22:1351-1360.
61. Xu G, Niki T, Virtanen I, Rogiers V, De Bleser P, Geerts A. Gene expression and synthesis of fibronectin isoforms in rat hepatic stellate cells. Comparison with liver parenchymal cells and skin fibroblasts. J Pathol 1997; 183:90-98.
62. De Bleser PJ, Niki T, Rogiers V, Geerts A. Transforming growth factor-beta gene expression in normal and fibrotic rat liver. J Hepatol 1997; 26:886-893.
63. De Bleser PJ, Niki T, Xu G, Rogiers V, Geerts A. Localization and cellular sources of activins in normal and fibrotic rat liver. Hepatology 1997; 26:905-912.
64. De Bleser PJ, Scott CD, Niki T, Xu G, Wisse E, Geerts A. Insulin-like growth factor II/mannose 6-phosphate-receptor expression in liver and serum during acute CCl4 intoxication in the rat. Hepatology 1996; 23:1530-1537.
65. Niki T, Schuppan D, De Bleser PJ, Vrijsen R, Pipeleers-Marichal M, Beyaert R, Wisse E, Geerts A. Dexamethasone alters messenger RNA levels but not synthesis of collagens, fibronectin, or laminin by cultured rat fat-storing cells. Hepatology 1996; 23:1673-1681.
66. Niki T, De Bleser PJ, Xu G, Van Den Berg K, Wisse E, Geerts A. Comparison of glial fibrillary acidic protein and desmin staining in normal and CCl4-induced fibrotic rat livers. Hepatology 1996; 23:1538-1545.
67. Niki T, Oka T, Shiga J, Takahashi K, Geerts A, Machinami R. Increased S-100 protein-immunoreactivity of Kupffer cells is associated with lymphohematological malignancy. Pathol Int 1995;45:742-747.
68. Niki T, Oka T, Shiga J, Machinami R. Kupffer cells in multiple organ failure --their activation as revealed by immunohistochemistry for lysozyme, alpha 1-antichymotrypsin, and lectins. Gen Diagn Pathol 1995;141:21-27.
69. De Bleser PJ, Jannes P, van Buul-Offers SC, Hoogerbrugge CM, van Schravendijk CF, Niki T, Rogiers V, Van den Brande JL, Wisse E, Geerts A. Insulin-like growth factor-II/mannose 6-phosphate receptor is expressed on CCl4-exposed rat fat-storing cells and facilitates activation of latent transforming growth factor-beta in cocultures with sinusoidal endothelial cells. Hepatology 1995; 21:1429-1437.
70. Kurita M, Niwa Y, Hamada E, Hata Y, Oshima M, Mutoh H, Shiina S, Nakata R, Ota S, Terano A, Sugimoto T, Ono M, Sawada T, Mori M, Niki T, Oka T Churg-Strauss-Syndrome (Allegic granulomatrous angitis) with multiple perforating ulcers of the small intestine, multiple ulcers of the colon, and mononeuritis multiplex. J Gastroenterology 1994; 29: 208-213.
71. Minami M, Kawauchi N, Itai Y, Niki T, Sasaki Y. Gastric tumors: radiologic-pathologic correlation and accuracy of T staging with dynamic CT. Radiology 1992;185:173-178.
72. Minami M, Itai Y, Ohtomo K, Ohnishi S, Niki T, Kokubo T, Yoshikawa K, Ilio M. Siderotic nodules in the spleen: MR imaging of portal hypertension. Radiology 1989;172:681-684.
73. Kitamura K, Nibu K, Asai M, Shitara N, Niki T. Chondromyxoid fibroma of the mastoid invading the occipital bone. Arch Otolaryngol Head Neck Surg 1989;115:384-386.

(72 articles; total impact factor=389.435; as of July 1, 2013)

主要論文10編(2004年まで)

1. Terasaki H, Niki T, Matsuno Y, Yamada T, Maeshima A, Asamura H, Hayabuchi N, Hirohashi S. Lung adenocarcinoma with mixed bronchiolo-alveolar and invasive components: clinicopathological features, subclassification by extent of invasive foci, and immunohistochemical characterization. Am J Surg Pathol 2003;27:937-951. (IF 4.9, 108 times cited)
2. Niki T, Kohno T, Iba S, Moriya Y, Takahashi Y, Saito M, Maeshima A, Yamada T, Matsuno Y, Fukayama M, Yokota J, Hirohashi S. Frequent co-localization of cox-2 and laminin-5 gamma2 chain at the invasive front of early-stage lung adenocarcinomas. Am J Pathol. 2002;160: 1129-1141. (IF 4.5, 61 times cited)
3. Rombouts K, Niki T, Greenwel P, Vandermonde A, Wielant A, Hellemans K, De Bleser P, Yoshida M, Schuppan D, Rojkind M, Geerts A. Trichostatin A, a histone deacetylase inhibitor, suppresses collagen synthesis and prevents TGF-beta(1)-induced fibrogenesis in skin fibroblasts. Exp Cell Res. 2002;278:184-197. (IF 3.6, 62 times cited)
4. Geerts A, Eliasson C, Niki T, Wielant A, Vaeyens F, Pekny M. Formation of normal desmin intermediate filaments in mouse hepatic stellate cells requires vimentin. Hepatology 2001; 33: 177-188. (IF 12.0, 34 times cited)
5. Tokunou M, Niki T, Eguchi K, Tsuda H, Yamada T, Matsuno Y, Kondo H, Saitoh Y, Imamura H, Hirohashi S. c-MET expression in myofibroblasts: role in autocrine activation and prognostic significance in lung adenocarcinoma. Am J Pathol 2001; 158: 1451-1463. (IF 4.5, 63 times cited)
6. Moriya Y, Niki T, Yamada T, Matsuno Y, Kondo H, Hirohashi S. Increased expression of laminin-5 and its prognostic significance in small-sized lung adenocarcinoma: an immunohistochemical analysis of 102 cases. Cancer 2001; 91: 1129-1141. (IF 5.2, 55 times cited)
7. Niki T, Iba S, Tokunou M, Yamada T, Matsuno Y, Hirohashi S. Expression of vascular endothelial growth factors A, B, C, and D and their relationships to lymph node status in lung adenocarcinoma. Clin Cancer Res 2000; 6: 2431-2439. (IF 7.8, 211 times cited)
8. Niki T, Rombouts K, De Bleser PJ, De Smet K, Rogiers V, Schuppan D, Yoshida M, Gabbiani G, Geerts A. A histone deacetylase inhibitor, trichostatin A, suppresses myofibroblastic differentiation of rat hepatic stellate cells in primary culture. Hepatology 1999;29:858-867. (IF 12.0, 102 times cited)
9. Niki T, Pekny M, Hellemans K, De Bleser PJ, Van Den Berg K, Vaeyens F, Quartier E, Schuit F, Geerts A. Class VI intermediate filament protein nestin is induced during activation of rat hepatic stellate cells. Hepatology 1999; 29: 520-527. (IF 12.0, 176 times cited)
10. Niki T, De Bleser PJ, Xu G, Van Den Berg K, Wisse E, Geerts A. Comparison of glial fibrillary acidic protein and desmin staining in normal and CCl4-induced fibrotic rat livers. Hepatology 1996; 23:1538-1545. (IF 12.0, 107 times cited)

(citation, as of Nov. 25, 2013)

主要論文10編(2005年以降)

1. Matsubara D, Kishaba Y, Ishikawa S, Sakatani T, Oguni S, Tamura T, Hoshino H, Sugiyama Y, Endo S, Murakami Y, Aburatani H, Fukayama M, Niki T. Lung Cancer with Loss of BRG1/BRM, shows Epithelial Mesenchymal Transition Phenotype and Distinct Histologic and Genetic Features. Cancer Sci 2013;104:266-273.
2. Matsubara D, Niki T. Epidermal growth factor receptor mutation and chemosensitivity. J Thorac Oncol 2012;4:771-772.
3. Matsubara D, Kanai Y, Ishikawa S, Ohara S, Yoshimoto T, Sakatani T, Oguni S, Tamura T, Kataoka H, Endo S, Murakami Y, Aburatani H, Fukayama M, Niki T. Identification of CCDC6-RET Fusion in the Human Lung Adenocarcinoma Cell Line, LC-2/ad. J Thorac Oncol. 2012;7:1872-1876.
4. Matsubara D, Ishikawa S, Oguni S, Aburatani H, Fukayama M, Niki T. Co-activation of epidermal growth factor receptor and c-MET defines a distinct subset of lung adenocarcinomas. Am J Pathol 2010;177:2191-2204.
5. Kishaba Y, Matsubara D, Niki T. Heterogenous Expression of nestin in myofibroblasts of various human tissues. Pathol Int 2010;60:378–385.
6. Matsubara D, Ishikawa S, Oguni S, Aburatani H, Fukayama M, Niki T. Molecular predictors of sensitivity to the MET inhibitor PHA665752 in lung carcinoma cells. J Thorac Oncol 2010;5:1317-1324.
7. Matsubara D, Morikawa T, Goto A, Nakajima J, Fukayama M, Niki T. Subepithelial myofibroblast in lung adenocarcinoma: a histologic indicator of excellent prognosis. Mod Pathol 2009;22:776-85.
8. Nakamura Y, Matsubara D, Goto A, Ota S, Oguni S, Ishikawa S, Aburatani H, Miyazawa K, Fukayama M, Niki T. Constitutive activation of c-Met is correlated with c-Met overexpression and dependent on cell-matrix adhesion in lung adenocarcinoma cell lines. Cancer Sci 2008;99:14-22.
9. Wang T, Niki T, Goto A, Ota S, Morikawa T, Nakamura Y, Ohara E, Ishikawa S, Aburatani H, Nakajima J, Fukayama M. Hypoxia increases the motility of lung adenocarcinoma cells A549 via activation of the epidermal growth factor receptor pathway. Cancer Sci 2007;98:506-11.
10. Nakamura Y, Niki T, Goto A, Morikawa T, Miyazawa K, Nakajima J, Fukayama M. c-Met activation in lung adenocarcinoma tissues: an immunohistochemical analysis. Cancer Sci. 2007;98:1006-13.
11. Matsubara D, Niki T, Ishikawa S, Goto A, Ohara E, Yokomizo T, Heizmann CW, Aburatani H, Moriyama S, Moriyama H, Nishimura Y, Funata N, Fukayama M Differential expression of S100A2 and S100A4 in lung adenocarcinomas: clinicopathologic significance, relationship to p53, and identification of their target genes. Cancer Sci 2005;96:844-57.

プロフィール・所属学会

経歴

1983年 東京大学医学部卒業
1987年 東京大学医学部病理学講座助手
1991年 Laboratory for Cell Biology and Histology, Free University of Brussels留学
1997年 国立がんセンター研究所病理部主任研究官
2000年 国立がんセンター研究所病理部室長
2001年 東京大学医学部人体病理学講座助教授
2005年 自治医科大学病理学講座教授

出身:徳島県(旧徳島大学教育学部付属中学卒、第26回生)

【著書】

呼吸器研修医ノート.診断と治療社.(分担執筆)
標準病理学. 医学書院.(編集、分担執筆)
標準臨床検査学.病理学・病理検査学(福嶋教授との共同編集、分担執筆)

【研究テーマ】

1. 肺癌、分子標的
2. 筋線維芽細胞、癌・間質相互作用、微小環境

【資格】

医師、医学博士
日本病理学会認定専門医
日本臨床細胞学会細胞診専門医

【所属学会】

日本病理学会評議員
日本癌学会評議員
日本肺癌学会評議員
日本臨床細胞学会会員
AACR (American Association for Cancer Research), active member
IASLC (International Association for the Study of Lung Cancer), member

【委員など】

日本肺癌学会国際委員会委員
肺癌取扱い規約病理診断委員会委員(2009-2016)
日本病理学会Pathology International 刊行委員
日本病理学会病理診断コンサルタント
国立がんセンターがん対策情報センター臨床試験・診療支援部 
病理診断コンサルテーション推進室コンサルタント
日本癌学会 Cancer Science Associate Editor
日本肺癌学会関東部会幹事
東京大学大学院医学系研究科非常勤講師
岡山大学医学部非常勤講師
日本歯科大学生命歯学部非常勤講師