The synergistic effect of minimum invasive anti-cancer therapy in combination with dendritic cell cancer vaccine

2011 Fiscal Year Final Research Report

• Project/Area Number: 21791332
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Thoracic surgery
• Research Institution: Tokyo Medical University
• Principal Investigator: SAJI Hisashi 東京医科大学, 医学部, 講師 (60420965)
• Project Period (FY): 2009 – 2011
• Keywords: 肺癌 / 腫瘍免疫 / 宿主免疫応答 / 樹状細胞癌ワクチン治療 / 光線力学的治療

Research Abstract

We previously reported the synergic effect of photodynamic therapy and dendritic cell cancer vaccine therapy for mouse cancer models(Saji H et al, Clin Cancer Res. 2006). In this program, we performed the preclinical research for the possible clinical application of minimum invasive anti-cancer therapy in combination with dendritic cell cancer vaccine.
It must be very essential to recognize the exact host immune-status against cancer for development of cancer immunotherapy. Expression of the transcription factor FOXP3 characterizes regulatory T cells that engage in the maintenance of immunological self-tolerance and immune homeostasis. First we analyzed the expression of FOXP3 positive lymphocytes in 50 non-small cell lung cancer(NSCLC) tissues and assessed the correlation between these expression and clinicopathological factors. There is no correlation between these expression and age or gender. Expression of FOXP3 positive lymphocytes were increased in adenocarcinoma compared with non-adenocarcinoma. There was positive correlation between these expression and lymph node metastasis. Therefore, we further study this analysis in additional 100 NSCLC tissues. Secondary, we have conducted the clinical cancer vaccine trial of intratumoral dendritic cell injection in combination with photodynamic therapy, radiofrequency ablation or chemotherapy for locally advanced non resectable NSCLC.

Research Products

• [Journal Article] Pathological vascular invasion and tumor differentiation predict cancer recurrence in stage IA non-small cell lung cancer after complete surgical resection (2012)
  • Author(s): Shimada Y, Saji H, Yoshida K, Kakihana M, Honda H, Nomura M, Usuda J, Kajiwara N, Ohira T, Ikeda N.
  • Journal Title: Thoracic Oncol
• [Journal Article] Do tumours located in the left lower lobe have worse outcomes in lymph node-positive non-small cell lung cancer than tumours in other lobes (2012)
  • Author(s): Kudo Y, Saji H, Shimada Y, Nomura M, Usuda J, Kajiwara N, Ohira T, Ikeda N.
  • Journal Title: Eur J Cardiothorac Surg
• [Journal Article] Prognostic impact of number of resected and involved lymph nodes at complete resection on survival in non-small cell lung cancer (2011)
  • Author(s): Saji H, Tsuboi M, Yoshida K, Kato Y, Nomura M, Matsubayashi J, Nagao T, Kakihana M, Usuda J, Kajiwara N, Ohira T, Ikeda N.
  • Journal Title: J Thorac Oncol Volume: 6 Pages: 1865-1871
• [Journal Article] Challenges and furture directions for clnical trials about surgical strategies for lung cancer in Japan(review in Japanese) (2011)
  • Author(s): Saji H, Ikeda N.
  • Journal Title: Journal of Clinical Surgery Volume: 66
• [Journal Article] Klotho is a novel biomarker for good survival in resected large cell neuroendocrine carcinoma of the lung (2011)
  • Author(s): Usuda J, Ichinose S, Ishizumi T, Ohtani K, Inoue T, Saji H, Kakihana M, Kajiwara N, Uchida O, Nomura M, Tsutsui H, Ohira T, Ikeda N.
  • Journal Title: Lung Cancer Volume: 72 Pages: 355-359
• [Journal Article] Clinical response of large cell neuroendocrine carcinoma of the lung to perioperative adjuvant chemotherapy (2010)
  • Author(s): Saji H, Tsuboi M, Matsubayashi J, Miyajima K, Shimada Y, Imai K, Kato Y, Usuda J, Kajiwara N, Uchida O, Ohira T, Hirano T, Mukai K, Kato H, Ikeda N.
  • Journal Title: Anticancer Drugs Volume: 21 Pages: 89-93
• [Journal Article] A phase III randomized trial of lobectomy versus limited resection for small-sized peripheral non-small cell lung cancer(JCOG0802/WJOG4607L) (2010)
  • Author(s): Nakamura K, Saji H, Nakajima R, Okada M, Asamura H, Shibata T, Nakamura S, Tada H, Tsuboi M.
  • Journal Title: Jpn J Clin Oncol Volume: 40 Pages: 271-274
• [Journal Article] The prognostic impact of main bronchial lymph node involvement in non-small cell lung carcinoma : suggestions for a modification of the staging system (2009)
  • Author(s): Shimada Y, Tsuboi M, Saji H, Miyajima K, Usuda J, Uchida O, Kajiwara N, Ohira T, Hirano T, Kato H, Ikeda N.
  • Journal Title: Ann Thorac Surg Volume: 88 Pages: 1583-1588
• [Journal Article] Klotho predicts good clinical outcome in patients with limited-disease small cell lung cancer who received surgery
  • Author(s): Usuda J, Ichinose S, Ishizumi T, Ohtani K, Inoue T, Saji H, Kakihana M, Kajiwara N, Uchida O, Nomura M, Ohira T, Ikeda N.
  • Journal Title: Lung Cancer
• [Presentation] 「I, II期非小細胞肺癌に対する外科療法」-情報の共有と知の創造- (2011)
  • Author(s): 佐治久
  • Organizer: 第52回日本肺癌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2011-11-04
• [Presentation] 胸部薄切CT所見に基づく肺野型早期肺癌の診断とその妥当性に関する前向き研究: 5年生存追跡結果の報告 (2011)
  • Author(s): 中嶋隆、鈴木健司, 小池輝明, 楠本昌彦, 浅村尚生, 永井完治, 多田弘人, 山下素弘, 光富徹哉, 池田徳彦, 佐治久, 坪井正博
  • Organizer: 第52回日本肺癌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2011-11-04
• [Presentation] 下葉原発非小細胞肺癌における上縦隔リンパ節郭清省略についての検討 (2011)
  • Author(s): 嶋田善久、佐治久, 石角太一郎, 萩原優, 垣花昌俊, 臼田実男, 本多英俊, 梶原直央, 大平達夫, 池田徳彦
  • Organizer: 第52回日本肺癌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2011-11-03
• [Presentation] 肺癌手術症例における術前縦隔N因子診断の成績 (2011)
  • Author(s): 石角太一郎、臼田実男, 嶋田善久, 萩原優, 佐治久, 垣花昌俊, 本多英俊, 梶原直央, 大平達夫, 池田徳彦
  • Organizer: 第52回日本肺癌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2011-11-03
• [Presentation] 神経内分泌肺癌におけるKotho発現と予後との関係 (2011)
  • Author(s): 臼田実男、石角太一郎, 一ノ瀬修二, 井上達哉, 大谷圭志, 佐治久, 垣花昌俊, 本多英俊, 梶原直央, 大平達夫, 池田徳彦
  • Organizer: ワークショップ、第52回日本肺癌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2011-11-03
• [Presentation] アンチエイジング遺伝子Klotho発現と神経内分泌肺癌の予後との関係 (2011)
  • Author(s): 臼田実男、石角太一郎, 一ノ瀬修二, 佐治久, 垣花昌俊, 梶原直央, 大平達夫, 池田徳彦
  • Organizer: 第64回日本胸部外科学会定期学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2011-10-12
• [Presentation] NM分類第7版における胸膜浸潤と予後の検討 (2011)
  • Author(s): 工藤勇人、佐治久, 前田純一, 一ノ瀬修二, 本多英俊, 垣花昌俊, 長瀬清亮, 臼田実男, 野村将春, 梶原直央, 大平達夫, 池田徳彦
  • Organizer: 第64回日本胸部外科学会定期学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2011-10-11
• [Presentation] Do Tumors Located in the Left Lower Lobe have Worse Outcome in Lymph Node-positive Non-small Cell Lung Cancer (2011)
  • Author(s): Kudo Y, Saji H, Shimada Y, Iwasaki K, Nomura M, Matsubayashi J, Kakihana M, Nagase S, Usuda J, Kajiwara N, Ohira T, Ikeda N.
  • Organizer: The 6th Biennial Meeting of Asian Thoracic Surgical Club
  • Place of Presentation: Busan, Korea
  • Year and Date: 2011-09-01
• [Presentation] Clinical value of intraoperative pleural lavage cytological positivity in lung cancer patients (2011)
  • Author(s): Kakihana M, Yoshida K, Taira M, Saji H, Usuda J, Kajiwara N, Ohira T, Ikeda N.
  • Organizer: 14th World Conference on Lung Cancer
  • Place of Presentation: Amsterdam, Netherland
  • Year and Date: 2011-07-07
• [Presentation] Prognostic value of visceral pleural invasion in the new TNM classification of non-small cell lung cancer (2011)
  • Author(s): Kudo Y, Saji H, Ichinose S, Nomura M, Matsubayashi J, Kataba H, Kahihana M, Nagase S, Usuda J, Kajiwara N, Ohira T, Ikeda N.
  • Organizer: 14th World Conference on Lung Cancer
  • Place of Presentation: Amsterdam, Netherland
  • Year and Date: 2011-07-07
• [Presentation] Prognostic significance of intratumoral vasucular invasion in non-small cell lung cancer-a candidate of pathological prognostic factors in the next TNM classification (2011)
  • Author(s): Saji H, Inoue T, Yamaguchi G, Kudo Y, Nomura M, Matsubayashi J, Kakihana M, Usuda J, Kajiwara N, Ohira T, Ikeda N.
  • Organizer: 14th World Conference on Lung Cancer
  • Place of Presentation: Amsterdam, Netherland
  • Year and Date: 2011-07-05
• [Presentation] 肺癌に対する光線力学的治療のメカニズム解明と適応拡大に関する研究 (2011)
  • Author(s): 臼田実男、一ノ瀬修二, 石角太一郎, 井上達哉, 大谷圭志, 本多英俊, 佐治久, 垣花昌俊, 梶原直央, 大平達夫, 池田徳彦
  • Organizer: 第34回日本呼吸器内視鏡学会学術集会
  • Place of Presentation: 浜松
  • Year and Date: 2011-06-16
• [Presentation] 非小細胞肺癌における原発巣部位と予後の関係～左下葉は予後不良因子か (2011)
  • Author(s): 工藤勇人、佐治久, 片場寛明, 一ノ瀬修二, 垣花昌俊, 長瀬清亮, 臼田実男, 野村将春, 梶原直央, 大平達夫, 池田徳彦
  • Organizer: 第28回日本呼吸器外科学会総会
  • Place of Presentation: 別府
  • Year and Date: 2011-05-12
• [Presentation] 肺癌手術後における早期再発症例の検討 (2011)
  • Author(s): 吉田浩一、平良真博, 工藤勇人, 本多英俊, 佐治久, 垣花昌俊, 臼田実男, 梶原直央, 大平達夫, 池田徳彦
  • Organizer: 第28回日本呼吸器外科学会総会
  • Place of Presentation: 別府
  • Year and Date: 2011-05-12
• [Presentation] The isolation of miRNA targeting EGFR gene in lung cancer (2011)
  • Author(s): Yamaguchi G, Ikeda N, Kuroda M, Ohira T, Uchida O, Kajiwara N, Usuda J, Kakihana M, Saji H, Takanashi M, Fujita K, Yoshida K, Kataba H, Iwasaki K, Tanaka M.
  • Organizer: American Association for Cancer Research 102th Annual Meeting
  • Place of Presentation: Orland, USA.
  • Year and Date: 2011-04-06
• [Presentation] Prognostic Value of Sialylated Glycoprotein KL-6 in Resected Non-Small Cell Lung Cancer (2010)
  • Author(s): Uchida O, Taira M, Saji H, Kakihana M, Usuda J, Kajiwara N, Ohira T, Ikeda N.
  • Organizer: 4th Asia Pacific Lung Cancer Conference
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2010-12-04
• [Presentation] Risk factor for recurrence in completely resected stage IA non-small cell lung cancer patients with tumors less than 2 cm in maximum dimension (2010)
  • Author(s): Kudo Y, Ichinose S, Kataba H, Saji H, Kakihana M, Usuda J, Kajiwara N, Uchida O, Ohira T, Ikeda N.
  • Organizer: 4th Asia Pacific Lung Cancer Conference
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2010-12-04
• [Presentation] Which is Superior Prognostic Factor of Total Number or Anatomical Location of Involved Lymph-Nodes(LNS) in Non-Small Cell Lung Cancer(NSCLC) (2010)
  • Author(s): Saji H, Inoue T, Yamaguchi G, Nomura M, Kakihana M, Usuda J, Kajiwara N, Uchida O, Ohira T, Ikeda N.
  • Organizer: 4th Asia Pacific Lung Cancer Conference
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2010-12-03
• [Presentation] 肺大細胞神経内分泌癌におけるアンチエイジング遺伝子Klotho発現の臨床的意義、ワークショップ (2010)
  • Author(s): 臼田実男、一ノ瀬修二, 大谷圭志, 井上達哉, 佐治久, 垣花昌俊, 梶原直央, 内田修, 大平達夫, 池田徳彦
  • Organizer: 第51回日本肺癌学会総会
  • Place of Presentation: 広島
  • Year and Date: 2010-11-04
• [Presentation] 肺神経内分泌癌に対する周術期補助抗癌剤治療の臨床的意義-当院での経験、ワークショップ (2010)
  • Author(s): 佐治久
  • Organizer: 第51回日本肺癌学会総会
  • Place of Presentation: 広島
  • Year and Date: 2010-11-03
• [Presentation] EGFR遺伝子を標的とするmiRNAの単離と解析 (2010)
  • Author(s): 山口学, 大平達夫, 岩崎賢太郎, 片場寛明, 井上達哉, 吉田浩一, 佐治久, 垣花昌俊, 臼田実男, 梶原直央, 内田修, 大野慎一郎, 高梨正勝, 黒田雅彦, 池田徳彦
  • Organizer: 第63回日本胸部外科学会定期学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2010-10-25
• [Presentation] Clinical outcome of large cell neuroendocrine carcinoma of the lung to pre or post operative adjuvant a single institutional report (2010)
  • Author(s): Saji H, Tsuboi M, Matsubayashi J, Miyajima K, Yoshida K, Shimada Y, Imai K, Kato Y, Usuda J, Kajiwara N, Ushida O, Ohira T, Kato H, Ikeda N.
  • Organizer: 9th International Conference of The Asian Clinical Oncology Society(ACOS)
  • Place of Presentation: Gifu, Japan
  • Year and Date: 2010-08-26
• [Presentation] N因子分類(解剖学的位置と転移個数)の方向性 (2010)
  • Author(s): 佐治久、池田徳彦
  • Organizer: 第25回日本肺癌学会ワークショップ
  • Place of Presentation: 東京
  • Year and Date: 2010-07-03
• [Presentation] The results and methods of EGFR mutation using specimen by endoscopy (2010)
  • Author(s): Ohira T, Yoshida K, Ichinose S, Nomura M, Saji H, Kakihana M, Honda H, Usuda J, Kajiwara N, Uchida O, Ikeda N.
  • Organizer: 16th World Congress for Bronchology
  • Place of Presentation: Budapest, Hungary
  • Year and Date: 2010-06-16
• [Presentation] Outcome of photodynamic therapy using NPe6 for bronchogenic carcinomas in central airways more than 1.0 cm in diameter (2010)
  • Author(s): Usuda J. Ichinose S, Ohtani K, Inoue T, Honda H, Saji H, Kakihana M, Kajiwara N, Ohira T, Uchida O, Ikeda N.
  • Organizer: 16th World Congress for Bronchology
  • Place of Presentation: Budapest, Hungary
  • Year and Date: 2010-06-15
• [Presentation] 末梢型肺癌に対する光線力学的治療の検討 (2010)
  • Author(s): 臼田実男、一ノ瀬修二, 大谷圭志, 本多英俊, 佐治久, 垣花昌俊, 梶原直央, 内田修, 大平達夫, 加藤治文, 池田徳彦
  • Organizer: 第33回日本呼吸器内視鏡学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2010-06-10
• [Presentation] 肺癌手術治療成績の向上をめざした基礎研究 (2010)
  • Author(s): 大平達夫、一ノ瀬修二、大谷圭志、小林慎吾、及川武史、佐治久、垣花昌俊、本多英俊、梶原直央、内田修、池田徳彦
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-04-10
• [Presentation] Prognostic impact of gene expression profile in early stage Non-small Cell Lung Cancer (2009)
  • Author(s): Saji H, Tsuboi M, Usuda J, Kajiwara N, Uchida O, Ohira T, Ikeda N.
  • Organizer: 13th World Conference on Lung Cancer
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2009-08-03
• [Presentation] Breast cancer resistant protein(BCRP) is a molecular determinant of the outcome of photodynamic therapy(PDT) for centrally located early lung cancer (2009)
  • Author(s): Usuda J, Ichinose S, Ishizumi T, Ohtani K, Maehara S, Kajiwara N, Saji H, Ohira T, Ikeda N.
  • Organizer: World Conference on Lung Cancer
  • Place of Presentation: San Francisco, USA.
  • Year and Date: 2009-08-02
• [Presentation] Impact of number of resected and involved lymph nodes(LN) at the time of surgical resection on the survival of non-small cell lung cacer(NSCLC) (2009)
  • Author(s): Saji H, Tsuboi M, Miyajima M, Ohira T, Ikeda N.
  • Organizer: American Society of Clinical Oncology, Annual Meeting
  • Place of Presentation: Orland, FL, USA.
  • Year and Date: 2009-05-30
• [Presentation] 肺癌におけるリンパ節郭清の意義-リンパ節郭清個数と転移個数およびその部位からの検討 (2009)
  • Author(s): 佐治久、宮島邦治, 一ノ瀬修二, 加藤靖文, 臼田実男, 梶原直央, 内田修, 大平達夫, 平野隆, 池田徳彦
  • Organizer: 第26回日本呼吸器外科学会総会
  • Year and Date: 2009-05-14
• [Presentation] A Gene Expression signature Predicts Prognosis of Patients with early stage Non-Small Cell Lung Cancer. (2009)
  • Author(s): Saji H, Tsuboi M, Usuda J, Nomura M, Ohira T, Ikeda N.
  • Organizer: American Association for Cancer Research, 100th Annual Meeting
  • Place of Presentation: Denver, CO, USA.
  • Year and Date: 2009-04-20
• [Presentation] microRNA profiles of lung cancer patients using Formalin-fixed, Paraffin-embedded tissue (2009)
  • Author(s): Ohira T, Usuda J, Ichinose S, Maehara S, Kuwajima Y, Saji H, Kakihana M, Nomura M, Kajiwara N, Uchida O, Hirano T, Ikeda N.
  • Organizer: American Association for Cancer Research, 100th Annual Meeting
  • Place of Presentation: Denver, CO, USA.
  • Year and Date: 2009-04-19
• [Remarks] 所属する教室のホームページにてその成果と現状を報告している。
  • URL: http://www.tokyo-med.ac.jp/surg1/