PI3K/AKT/mTOR pathway in pulmonary carcinoid tumours

Zhang, Zixuan; Wang, Mengzhao

doi:10.3892/ol.2017.6331

Cited by 14 publications

(17 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DNA from 54 primary lung NETs, including low grade (17 typical carcinoids (TCs) and 8 atypical carcinoids (ACs)) and high grade NETs (17 large cell neuroendocrine carcinomas and 12 small cell neuroendocrine carcinomas), was sequenced. Five missense mutations in mTOR ( n = 1), TSC1 ( n = 1) and TSC2 genes ( n = 3) were identified, but only in low grade tumors [ 80 ].…”

Section: Mtor and Netsmentioning

confidence: 99%

The Role of mTOR in Neuroendocrine Tumors: Future Cornerstone of a Winning Strategy?

Lamberti

Brighi

Maggio

et al. 2018

IJMS

View full text Add to dashboard Cite

The mechanistic target of rapamycin (mTOR) is part of the phosphoinositide-3-kinase (PI3K)/protein kinase B (AkT)/mTOR pathway and owes its name to the inhibitory effect of rapamycin. The mTOR has a central converging role for many cell functions, serving as a sensor for extracellular signals from energy status and nutrients availability, growth factors, oxygen and stress. Thus, it also modulates switch to anabolic processes (protein and lipid synthesis) and autophagy, in order to regulate cell growth and proliferation. Given its functions in the cell, its deregulation is implicated in many human diseases, including cancer. Its predominant role in tumorigenesis and progression of neuroendocrine tumors (NETs), in particular, has been demonstrated in preclinical studies and late clinical trials. mTOR inhibition by everolimus is an established therapeutic target in NETs, but there are no identified predictive or prognostic factors. This review is focused on the role of mTOR and everolimus in NETs, from preclinical studies to major clinical trials, and future perspectives involving mTOR in the treatment of NETs.

show abstract

Section: Mtor and Netsmentioning

confidence: 99%

The Role of mTOR in Neuroendocrine Tumors: Future Cornerstone of a Winning Strategy?

Lamberti

Brighi

Maggio

et al. 2018

IJMS

View full text Add to dashboard Cite

show abstract

“…Accordingly, no guidelines on the treatment of these tumors are available at present. Currently, biologic-targeted therapies derived from engineered gene products play a particularly important role in the treatment of well-differentiated NETs occurring in the pancreas, gastrointestinal tract and lung [7, 8]. In 2011, the multiple receptor tyrosine kinase (RTK) inhibitor sunitinib was approved by the FDA to treat advanced, progressive, well-differentiated pancreatic NETs [7].…”

Section: Introductionmentioning

confidence: 99%

Clinicopathological characteristics and molecular abnormalities of primary grade 2 neuroendocrine tumors of the cervix

Zhu

Chen

et al. 2019

Diagn Pathol

View full text Add to dashboard Cite

Background Primary grade 2 neuroendocrine tumors of the cervix in female patients are rare and have a highly aggressive clinical course. This study is aimed to analyse the diagnosis, genetic changes, management and prognosis of these tumors and investigate whether the genetic alterations could provide more useful information to guide the molecular characterization and potential individualized treatment of grade 2 cervical neuroendocrine tumors. Methods The clinical records of all three patients diagnosed as primary grade 2 neuroendocrine tumors of the cervix in Peking Union Medical College Hospital (PUMCH) from 2011 to 2018 were reviewed retrospectively. We investigated the morphology, immunophenotype and molecular abnormalities of all the cases. The follow-up data were also collected. Results The age of the patients ranged from 46 to 69 years. All cases were in stage II and treated with surgery. The microscopic examination showed that the tumors took the form of nest-like, trabecular, sheet-like, “single file” strands or rosette-like structures. The mitotic figures ranged from 2 to 5 in every 10 high-power fields, and necrotic foci were observed in one case. Immunohistochemically, the tumor cells were positive for AE1/AE3, Cg A, Syn, CD56, P16, CAM5.2, and PGP9.5 and negative for ER, PR, P63, P40, CK7, and CK20. The expression of P53 showed as normal/wild-type pattern, and the proliferation index of Ki-67 ranged from 2 to 7%. A total of 560 genes were sequenced by next-generation sequencing for each patient, and nonsynonymous somatic mutations were identified in the three cases. Non-frameshift insertions of the MAGI1 and SLC45A were both observed in case 1, while we only observed the non-frameshift insertion of the MAGI1 in case 2 and the non-frameshift insertion of the SLC45A in case 3. Case 1 was treated with chemoradiotherapy before and after surgery. Cases 2 and 3 were treated with chemotherapy before and after surgery. The follow-up time ranged from 27 to 74 months. Cases 2 and 3 survived, while case 1 died. Conclusion Cervical grade 2 neuroendocrine tumors are extremely rare. We presented the first mutation profile revealed by whole exome sequencing in a series of grade 2 cervical NETs along with their clinicopathological characteristics. Their genetic changes are different from those that take place in the gastrointestinal tract, pancreas and lung, which have gene changes in VEGF, RTKs or the mTOR signalling pathway. While changes in MAGI1 and SLC45L3 were observed in two of our cases and the case who had the gene changes of both MAGI1 and SLC45L3 died because of metastases to the liver and bone. The genetic alterations may provide more useful information to guide the molecular characterization and potential individualized treatment of grade 2 cervical neuroendocrine tumors.

show abstract

“…Rapamycin is a special prophylactic for the mammalian target of rapamycin (mTOR), which binds fk506-binding protein 12 kDa (FKBP12) to form a molecular complex that inhibits mTOR activity [ 11 ]. Abnormal activation of mTOR can lead to the occurrence of a wide variety of tumors [ 12 ]. Moreover, the promotion of autophagy linked to mTOR inhibition may mediate some effects of mTOR on cancer.…”

Section: Introductionmentioning

confidence: 99%

Rapamycin inhibits proliferation and induces autophagy in human neuroblastoma cells

et al. 2018

View full text Add to dashboard Cite

Objective To investigate the effect of Rapamycin on proliferation and autophagy in human neuroblastoma (NB) cell lines and to elucidate the possible mechanism. Methods NB cells were treated with different concentrations of Rapamycin. Cell counting kit-8 (CCK-8) was used to measure proliferation, and flow cytometry (FCM) was used to analyze the cell cycle. EM was used to observe cell morphological changes. Western blotting (WB) was performed to detect the expression of Beclin-1, LC3-I/II, P62, mammalian target of Rapamycin (mTOR), and p-mTOR. Results Rapamycin inhibited the spread of NB cells in a dose- and time-dependent manner and arrested the cell cycle at the G0/G1 phase. EM showed autophagosomes in NB cells treated with Rapamycin. The WB results showed that the expression levels of Beclin-1 and LC3-II/LC3-I were significantly elevated in NB cells treated with Rapamycin, while the expression levels of P62, mTOR, and p-mTOR proteins were significantly reduced compared with the control cells (P<0.05). Conclusion Rapamycin inhibits cell proliferation and induces autophagy in human NB cell lines. The mechanism may be related to suppression of the mTOR signaling pathway.

show abstract

PI3K/AKT/mTOR pathway in pulmonary carcinoid tumours

Cited by 14 publications

References 37 publications

The Role of mTOR in Neuroendocrine Tumors: Future Cornerstone of a Winning Strategy?

The Role of mTOR in Neuroendocrine Tumors: Future Cornerstone of a Winning Strategy?

Clinicopathological characteristics and molecular abnormalities of primary grade 2 neuroendocrine tumors of the cervix

Rapamycin inhibits proliferation and induces autophagy in human neuroblastoma cells

Contact Info

Product

Resources

About