Tropomyosin-related kinase B inhibitor has potential for tumor regression and relapse prevention in pulmonary large cell neuroendocrine carcinoma

Seiichi Odate, Hideya Onishi, Katsuya Nakamura, Masayuki Kojima, Akihiko Uchiyama, Masato Kato, Mitsuo Katano

Research output: Contribution to journalArticle

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Abstract

Large cell neuroendocrine carcinoma (LCNEC) has an especially poor prognosis, and an effective therapeutic strategy has yet to be established. We have previously shown that the expressions of tropomyosin-related kinase B (TRKB) and brain-derived neurotrophic factor (BDNF) are high in LCNEC and that TRKB/BDNF signaling is involved in the proliferation, tumorigenesis, and invasive nature of LCNEC. Therefore, TRKB/BDNF signaling may offer a potential therapeutic target for LCNEC treatment. In the present study, we evaluated whether the TRKB tyrosine kinase inhibitor, k252a, has effects on tumor regression and relapse prevention on LCNEC, using a murine xenograft model. The LCNEC cell line and NCI-H810 cells were subcutaneously implanted into the flanks or intrathoracically injected into the bilateral pleural cavities of BALB/c nude mice. k252a significantly inhibited tumor volume, expression of matrix metalloproteinases and the formation of pleural dissemination by LCNEC. These results suggest that k252a has potential for tumor regression and relapse prevention in LCNEC. Since many patients with LCNEC suffer through the use of ineffective therapeutic strategies, a clinical trial using the TRKB inhibitor for LCNEC is urgently required.

Original languageEnglish
Pages (from-to)3699-3704
Number of pages6
JournalAnticancer research
Volume33
Issue number9
Publication statusPublished - Sep 1 2013

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Neuroendocrine Carcinoma
Large Cell Carcinoma
Secondary Prevention
Lung
Neoplasms
Brain-Derived Neurotrophic Factor
tropomyosin kinase
Pleural Cavity
Neuroendocrine Cells
Therapeutic Uses
Tumor Burden
Matrix Metalloproteinases
Heterografts
Nude Mice
Protein-Tyrosine Kinases
Carcinogenesis
Therapeutics
Clinical Trials

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Tropomyosin-related kinase B inhibitor has potential for tumor regression and relapse prevention in pulmonary large cell neuroendocrine carcinoma. / Odate, Seiichi; Onishi, Hideya; Nakamura, Katsuya; Kojima, Masayuki; Uchiyama, Akihiko; Kato, Masato; Katano, Mitsuo.

In: Anticancer research, Vol. 33, No. 9, 01.09.2013, p. 3699-3704.

Research output: Contribution to journalArticle

Odate, Seiichi ; Onishi, Hideya ; Nakamura, Katsuya ; Kojima, Masayuki ; Uchiyama, Akihiko ; Kato, Masato ; Katano, Mitsuo. / Tropomyosin-related kinase B inhibitor has potential for tumor regression and relapse prevention in pulmonary large cell neuroendocrine carcinoma. In: Anticancer research. 2013 ; Vol. 33, No. 9. pp. 3699-3704.
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