Expression of an activated mammalian target of rapamycin (mTOR) in gastroenteropancreatic neuroendocrine tumors View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2009-08-06

AUTHORS

Takashi Shida, Takashi Kishimoto, Mitsuko Furuya, Takashi Nikaido, Keiji Koda, Shigetsugu Takano, Fumio Kimura, Hiroaki Shimizu, Hiroyuki Yoshidome, Masayuki Ohtsuka, Tohru Tanizawa, Yukio Nakatani, Masaru Miyazaki

ABSTRACT

AimsGastroenteropancreatic neuroendocrine tumors are rare, and the current WHO classification divides this tumor entity into well-differentiated (neuro)endocrine tumors, well-differentiated (neuro)endocrine carcinomas, and poorly differentiated (neuro)endocrine carcinomas. Poorly differentiated (neuro)endocrine carcinoma is extremely aggressive, and no appropriate therapeutic approach has been established. The mammalian target of rapamycin (mTOR), an important regulator of cell proliferation and protein translation, is activated in various malignancies. Recent phase II trial has revealed the efficacy of mTOR inhibitor (RAD001; everolimus) against low-to-intermediate grade neuroendocrine tumors. However, the beneficial role of mTOR inhibitor against poorly neuroendocrine carcinoma remains uncertain. The purpose of the present study was to determine the activation of mTOR in gastropancreatic neuroendocrine tumors, especially in poorly differentiated neuroendocrine carcinomas.MethodsExpression of p-mTOR(Ser2448) was assessed by immunohistochemistry in 20 gastropancreatic neuroendocrine tumors (seven well-differentiated neuroendocrine tumors, four well-differentiated neuroendocrine carcinomas, and nine poorly differentiated neuroendocrine carcinomas). Double immunohistochemistry was performed with p-Akt for patients with high p-mTOR expression.ResultsExpression of mTOR was seen in 9 (45%) of 20 gastroenteropancreatic neuroendocrine tumors. High expression of p-mTOR was seen in 6 (67%) of 9 poorly differentiated neuroendocrine carcinomas which was higher than the expression rate of well-differentiated neuroendocrine tumors and carcinomas, 3 (27%) of 11. All large cell neuroendocrine carcinomas showed high p-mTOR expression. Some tumor cells showed positive staining for p-mTOR co-expressed p-Akt.ConclusionsHigh expression rate of p-mTOR in poorly differentiated neuroendocrine carcinomas (large-cell type) may suggest the potential role of mTOR inhibitors as effective therapeutic agents for this highly malignant disease. More... »

PAGES

889-893

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Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00280-009-1094-6

DOI

http://dx.doi.org/10.1007/s00280-009-1094-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1048417181

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19657638


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50 expression
51 expression rate
52 gastroenteropancreatic neuroendocrine tumors
53 gastropancreatic neuroendocrine tumors
54 grade neuroendocrine tumors
55 high expression
56 high p-mTOR expression
57 immunohistochemistry
58 important regulator
59 inhibitors
60 intermediate-grade neuroendocrine tumors
61 large cell neuroendocrine carcinoma
62 mTOR
63 mTOR inhibitors
64 malignancy
65 malignant disease
66 mammalian target
67 neuroendocrine carcinoma
68 neuroendocrine tumors
69 p-Akt
70 p-mTOR
71 p-mTOR expression
72 patients
73 phase II trial
74 positive staining
75 potential role
76 present study
77 proliferation
78 protein translation
79 purpose
80 rapamycin
81 rate
82 recent phase II trial
83 regulator
84 role
85 staining
86 study
87 target
88 therapeutic agents
89 therapeutic approaches
90 translation
91 trials
92 tumor cells
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