Development and clinical application of gene therapy of the advanced and recurrent head and neck cancer using transformed lactobacillus

• Project/Area Number: 23659791
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Tohoku University
• Principal Investigator: ASADA Yukinori 東北大学, 医学(系)研究科(研究院), 非常勤講師 (70436103)
• Co-Investigator(Kenkyū-buntansha): SHIGA Kiyoto 岩手医科大学, 医学部, 教授 (10187338)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 組換え体乳酸菌 / 頭頸部癌 / 腫瘍免疫 / 遺伝子治療 / サイトカイン / 頭頸部扁平上皮癌

Research Abstract

Two cell lines originated from head and neck squamous cell carcinoma, HSC2 and SAS were used to make transfered tumors on the back of nude mice. We administered two kinds of transformed lactobacillus casei into which IL2 gene and only vector plasmids were introduced. We used 5-day consecutive administration schedule. IL2-introduce lactobacillus showed significant tumor suppressive effects on SAS and HSC2. On the other hand, vector plasmid-introduce lactobacillus showed suppressive effects on HSC2. One nude mouse showed complete regression of the HSC2 tumor against IL2-introduce lactobacillus. Serum level of TNFa, IL12, and so on were significantly elevated in the lactobacillus administrated mice indicating the Th1 type immune response. Lactobacilli were observed in the tumor tissue of the mice, but was never observed in primary organs such as lung, liver, kidney.

Research Products

• [Journal Article] Matched-pair analysis in patients with advanced oropharyngeal cancer: surgery versus concurrent chemoradiotherapy. (2013)
  • Author(s): Kano S, Homma A, Hayashi R, Kawabata K, Yoshino K, Iwae S, Hasegawa Y, Nibu K, Kato T, Shiga K, Matsuura K, Monden N, Fujii M.
  • Journal Title: Oncology Volume: 84 Issue: 5 Pages: 290-298
  • DOI: 10.1159/000346908
  • Peer Reviewed
• [Journal Article] Bach1 is critical for the transformation of mouse embryonic fibroblast by RasV12 and maintains ERK signaling (2012)
  • Author(s): Nakanome A, Brydoun A, Matsumoto M, Ota K, Funayama R, Nakayama K, Ono M, Shiga K, Kobayashi T, Igarashi K
  • Journal Title: Oncogene Volume: 32 Issue: 27 Pages: 3231-3245
  • DOI: 10.1038/onc.2012.336
  • Peer Reviewed
• [Journal Article] Malignant melanoma of the head and neck : A multi-institutional retrospective analysis of cases in Northern Japan (2012)
  • Author(s): Shiga K, Ogawa T, Kobayashi T, Ueda S, Kondo A, Nanba A, Kuwashima S, Asada Y, Suzuki S, Nagahashi T, Takahashi M, Suzuki M, Ishida A, Watanabe K, Harabuchi Y, Himi T, Shinkawa H, Sato H, Saijyo S, Fukuda S, Tanaka K, Ishikawa K, Omori K, Aoyagi M, Hashimoto S
  • Journal Title: Head Neck Volume: (in press) Issue: 11 Pages: 1537-1541
  • DOI: 10.1002/hed.21984
  • Peer Reviewed
• [Journal Article] Difficulty of the differential diagnosis of basal cell adenoma and basal cell adenocarcinoma of parotid gland by magnetic resonance imaging: case reports and literature review (2012)
  • Author(s): Kojima I, Sakamoto M, Watanabe M,Takahashi S, Mugikura S, Shiga K, Iikubo M, Yamamura MJ, Sasano T.
  • Journal Title: Oral Radiol Volume: 28 Issue: 1 Pages: 24-31
  • DOI: 10.1007/s11282-011-0076-7
  • Peer Reviewed
• [Journal Article] miR-34a is downregulated in cis-diamminedichloroplatinum treated sinonasal squamous cell carcinoma patients with poor prognosis (2012)
  • Author(s): Takenori Ogawa, Yuriko Saiki, Kiyoto Shiga, Na Chen, Shinichi Fukushige, Makoto Sunamura, Hiroki Nagase, Sho Hashimoto, Kazuto Matsuura, Shigeru Saijo, Toshimitsu Kobayashi and Akira Horii
  • Journal Title: Cancer Sci Volume: 103 Pages: 1737-1743
  • Peer Reviewed
• [Journal Article] Differences between Oral Cancer and Cancer of the Pharynx & Larynx on Molecular level. (2011)
  • Author(s): Kiyoto Shiga, Takenori Ogawa, Katsunori Katagiri, Fumiaki Yoshida, Masaru Tateda, Toshimitsu Kobayashi.
  • Journal Title: Oncology Letters Volume: 3 Pages: 238-243
  • Peer Reviewed
• [Journal Article] Distinct Features of Second Primary Malignancies in Head and Neck Cancer Patients in Japan. (2011)
  • Author(s): Kiyoto Shiga, Masaru Tateda, Katsunori Katagiri, Ayako Nakanome, Takenori Ogawa, Yukinori Asada, Kengo Kato and Toshimitsu Kobayashi.
  • Journal Title: Tohoku J Exp Med Volume: 225 Pages: 5-12
  • NAID: 10029508189
  • Peer Reviewed