mTOR inhibitors and their clinical application in cervical, endometrial and ovarian cancers: A critical review

Husseinzadeh, Nader; Husseinzadeh, Holleh

doi:10.1016/j.ygyno.2014.02.017

Cited by 97 publications

(64 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although mutations of mTOR itself have not been reported, mutations in components of mTOR-related signaling pathways have frequently been described in various human malignancies. Notably, tumor cells with mutations in p53 or PTEN, found in more than 50% of human tumors, suggesting that inhibition of mTOR signaling might be a potential tumor-selective therapeutic strategy (Husseinzadeh et al, 2014). We found that oridonin inhibited the phosphorylation of mTOR in SKOV3 ovarian cells, but did not affect the levels of total mTOR proteins.…”

Section: Discussionmentioning

confidence: 67%

Oridonin Suppresses Proliferation of Human Ovarian Cancer Cells via Blockage of mTOR Signaling

Xiao¹,

Chen²,

Qin³

et al. 2016

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Oridonin, an ent-kaurane diterpenoid compound isolated from the traditional Chinese herb Rabdosia rubescens, has shown various pharmacological and physiological effects such as anti-tumor, anti-bacterial, and anti-inflammatory properties. However, the effect of oridonin on human ovarian cancer cell lines has not been determined. In this study, we demonstrated that oridonin inhibited ovarian cancer cell proliferation, migration and invasion in a dose-dependent manner. Furthermore, we showed oridonin inhibited tumor growth of ovarian cancer cells (SKOV3) in vivo. We then assessed mechanisms and found that oridonin specifically abrogated the phosphorylation/activation of mTOR signaling. In summary, our results indicate that oridonin is a potential inhibitor of ovarian cancer by blocking the mTOR signaling pathway. Keywords

show abstract

Section: Discussionmentioning

confidence: 67%

Oridonin Suppresses Proliferation of Human Ovarian Cancer Cells via Blockage of mTOR Signaling

Xiao¹,

Chen²,

Qin³

et al. 2016

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

show abstract

“…However, Poetsch et al 27 demonstrated PTEN mutations in 23% of head and neck SCC tumor samples, and Kurose et al 28 found intragenic PTEN mutations in 15% (3/20) of cervical tumors. PTEN mutations were frequently found in cancers arising from the endometrium 29,30 , brain 31 and prostate 32 . Rashmi et al 33 found results with activating PIK3CA (E545K, E542K) and inactivating PTEN (R233) mutations were identified in human cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

PTEN expression in patients with carcinoma of the cervix and its association with p53, Ki-67 and CD31

Loures¹,

Cândido²,

Vidigal³

et al. 2014

Rev. Bras. Ginecol. Obstet.

View full text Add to dashboard Cite

PURPOSE: To investigate protein expression and mutations in phosphatase and tensin homolog (PTEN) in patients with stage IB cervical squamous cell carcinoma (CSCC) and the association with clinical-pathologic features, tumor p53 expression, cell proliferation and angiogenesis. METHODS: Women with stage IB CSCC (n=20 -Study Group) and uterine myoma (n=20 -Control Group), aged 49.1±1.7 years (mean±standard deviation, range 27-78 years), were prospectively evaluated. Patients with cervical cancer were submitted to Piver-Rutledge class III radical hysterectomy and pelvic lymphadenectomy and patients in the Control Group underwent vaginal hysterectomy. Tissue samples from the procedures were stained with hematoxylin and eosin for histological evaluation. Protein expression was detected by immunohistochemistry. Staining for PTEN, p53, Ki-67 and CD31 was evaluated. The intensity of PTEN immunostaining was estimated by computer-assisted image analysis, based on previously reported protocols. Data were analyzed using the Student's t-test to evaluate significant differences between the groups. Level of significance was set at p<0.05. RESULTS: The PTEN expression intensity was lower in the CSCC group than in the Control (benign cervix) samples (150.5±5.2 versus 204.2±2.6; p<0.001). Our study did not identify any mutations after sequencing all nine PTEN exons. PTEN expression was not associated with tumor expression of p53 (p=0.9), CD31 (p=0.8) or Ki-67 (p=0.3) or clinical-pathologic features in patients with invasive carcinoma of the cervix. CONCLUSIONS: Our findings demonstrate that the PTEN protein expression is significantly diminished in CSCC.

show abstract

“…Patient 3, whose disease progressed, had a tumor lacking smooth muscle actin or desmin positivity, which has been noted in previous studies in PEComas with a transcription factor binding to IGHM enhancer 3 (TFE3) fusion gene product instead of mTOR pathway alterations (13), and this may explain the lack of response to temsirolimus. Additionally, approximately 75% of sporadic PEComas have alterations in TORC2, which in renal cell carcinomas is relatively more resistant to mTOR inhibitors (14,15). Testing for the TFE3 fusion gene product (Xp11) should be considered in patients with malignant uterine PEComas, as combination treatment with vascular endomethial growth factoror phosphatidylinositol-3-kinase-directed biological therapies may be more effective in this group.…”

Section: Discussionmentioning

confidence: 99%

Treatment of Advanced Malignant Uterine Perivascular Epithelioid Cell Tumor with mTOR Inhibitors: Single-institution Experience and Review of the Literature

Starbuck

Drake

Budd

et al. 2016

View full text Add to dashboard Cite

mTOR inhibitors and their clinical application in cervical, endometrial and ovarian cancers: A critical review

Cited by 97 publications

References 59 publications

Oridonin Suppresses Proliferation of Human Ovarian Cancer Cells via Blockage of mTOR Signaling

Oridonin Suppresses Proliferation of Human Ovarian Cancer Cells via Blockage of mTOR Signaling

PTEN expression in patients with carcinoma of the cervix and its association with p53, Ki-67 and CD31

Treatment of Advanced Malignant Uterine Perivascular Epithelioid Cell Tumor with mTOR Inhibitors: Single-institution Experience and Review of the Literature

Contact Info

Product

Resources

About