scholarly journals Metastatic role of mammalian target of rapamycin signaling activation by chemoradiotherapy in advanced rectal cancer

2020 ◽  
Vol 111 (4) ◽  
pp. 1291-1302
Author(s):  
Hiroshi Shiratori ◽  
Kazushige Kawai ◽  
Masamichi Okada ◽  
Hiroaki Nozawa ◽  
Keisuke Hata ◽  
...  
2010 ◽  
Vol 17 (4) ◽  
pp. 977-987 ◽  
Author(s):  
Luisella Righi ◽  
Marco Volante ◽  
Ida Rapa ◽  
Veronica Tavaglione ◽  
Frediano Inzani ◽  
...  

Among alternative therapeutic strategies in clinically aggressive neuroendocrine tumors (NETs) of the lung, promising results have been obtained in experimental clinical trials with mammalian target of rapamycin (mTOR) inhibitors, though in the absence of a proven mTOR signaling activation status. This study analyzed the expression of phosphorylated mTOR (p-mTOR) and its major targets, the ribosomal p70S6-kinase (S6K) and the eukaryotic initiation factor 4E-binding protein 1 (4EBP1) in a large series of 218 surgically resected, malignant lung NETs, including 24 metastasizing typical carcinoids, 73 atypical carcinoids, 60 large cell neuroendocrine carcinomas (LCNECs), and 61 small cell carcinomas (SCLCs). By immunohistochemistry, low-to-intermediate-grade tumors as compared with high-grade tumors showed higher levels of p-mTOR and phosphorylated S6K (p-S6K) (P<0.001), at variance with phosphorylated 4EBP1 (p-4EBP1), which was mainly expressed in LCNECs and SCLCs (P<0.001). The activated status of mTOR pathway was proved by the strong correlation of p-mTOR with p-S6K and somatostatin receptor(s). Western blot analysis of NET tumor samples confirmed such findings, and differential sensitivity to mTOR inhibition according to mTOR pathway activation characteristics was determined in two lung carcinoid cell lines in vitro. None of the investigated molecules had an impact on survival. However, in low-grade tumors, low p-mTOR expression correlated with lymph node metastases (P=0.016), recurrent disease, and survival (P=0.005). In conclusion, these data demonstrate a differential mTOR activation status in the spectrum of pulmonary NETs, possibly suggesting that mTOR pathway profiling might play a predictive role in candidate patients for mTOR-targeted therapies.


2015 ◽  
Vol 114 (11) ◽  
pp. 969-981 ◽  
Author(s):  
Esther López ◽  
Alejandro Berna-Erro ◽  
Javier J. López ◽  
María P. Granados ◽  
Nuria Bermejo ◽  
...  

SummaryThe function of the mammalian target of rapamycin (mTOR) is upregulated in response to cell stimulation with growing and differentiating factors. Active mTOR controls cell proliferation, differentiation and death. Since mTOR associates with different proteins to form two functional macromolecular complexes, we aimed to investigate the role of the mTORI and mTOR2 complexes in MEG-01 cell physiology in response to thrombopoietin (TPO). By using mTOR antagonists and overexpressing FKBP38, we have explored the role of both mTOR complexes in proliferation, apoptosis, maturation-like mechanisms, endoplasmic reticulum-stress and the intracellular location of both active mTOR complexes during MEG-01 cell stimulation with TPO. The results demonstrate that mTOR1 and mTOR2 complexes play different roles in the physiology of MEG-01 cells and in the maturation-like mechanisms; hence, these findings might help to understand the mechanism underlying generation of platelets.


Author(s):  
Evgeniy Panzhinskiy ◽  
Bruce Culver ◽  
Jun Ren ◽  
Debasis Bagchi ◽  
Sreejayan Nair

2021 ◽  
Vol 13 (11) ◽  
pp. 1632-1647
Author(s):  
Katharina Joechle ◽  
Jessica Guenzle ◽  
Claus Hellerbrand ◽  
Pavel Strnad ◽  
Thorsten Cramer ◽  
...  

2011 ◽  
Vol 27 (Supplement) ◽  
pp. OP04_2
Author(s):  
Koichi Nagashima ◽  
Takeshi Yamashita ◽  
Akiko Sekiguchi ◽  
Ichiro Watanabe ◽  
Atsushi Hirayama

2015 ◽  
Vol 5 (4) ◽  
pp. 667-680 ◽  
Author(s):  
Tatiana V. Kudryashova ◽  
Dmitry A. Goncharov ◽  
Andressa Pena ◽  
Kaori Ihida-Stansbury ◽  
Horace DeLisser ◽  
...  

2018 ◽  
Vol 32 (4) ◽  
pp. 371-376 ◽  
Author(s):  
Dimitrios Giannoulopoulos ◽  
Constantinos Nastos ◽  
Maria Gavriatopoulou ◽  
Antonios Vezakis ◽  
Dionysios Dellaportas ◽  
...  

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