Dataset Information

Inhibition of survivin reduces HIF-1?, TGF-?1 and TFE3 in salivary adenoid cystic carcinoma.

ABSTRACT: In the present study, we explored the expression and correlation of survivin with HIF-1?, TGF-?1 and TFE3 in adenoid cystic carcinoma (AdCC). The expression of survivin, HIF-1?, TGF-?1 and TFE3 was assessed by immunohistochemical staining of a tissue microarray containing tissue samples of normal salivary gland (NSG), pleomorphic adenoma (PA) and AdCC. Correlation analysis of these proteins revealed that increased survivin expression was associated with the overexpression of HIF-1? (P<0.001, r?=?0.5599), TGF-?1 (P<0.001, r?=?0.6616) and TFE3 (P<0.001, r?=?0.7747). The expression of survivin, HIF-1?, TGF-?1 and TFE3 was not correlated with the pathological type of human AdCC (P>0.05). Selective inhibition of survivin by YM155 and siRNA significantly reduced human SACC-83 cell proliferation, with the corresponding decrease in expression of HIF-1?, TGF-?1 and TFE3. The data indicate that the overexpression of survivin in AdCC is related to HIF-1?, TGF-?1 and TFE3. We hypothesize from these findings that the inhibition of survivin may be a novel strategy for neoadjuvant chemotherapeutic and radiosensitive treatment of AdCC.

SUBMITTER: Wang YF

PROVIDER: S-EPMC4259474 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Inhibition of survivin reduces HIF-1α, TGF-β1 and TFE3 in salivary adenoid cystic carcinoma.

Wang Yu-Fan YF Ma Si-Rui SR Wang Wei-Ming WM Huang Cong-Fa CF Zhao Zhi-Li ZL Liu Bing B Zhang Wen-Feng WF Zhao Yi-Fang YF Zhang Lu L Sun Zhi-Jun ZJ

PloS one 20141208 12

In the present study, we explored the expression and correlation of survivin with HIF-1α, TGF-β1 and TFE3 in adenoid cystic carcinoma (AdCC). The expression of survivin, HIF-1α, TGF-β1 and TFE3 was assessed by immunohistochemical staining of a tissue microarray containing tissue samples of normal salivary gland (NSG), pleomorphic adenoma (PA) and AdCC. Correlation analysis of these proteins revealed that increased survivin expression was associated with the overexpression of HIF-1α (P<0.001, r = ...[more]

PMID: 25485635

Similar Datasets

Project description:Adenoid cystic carcinoma (ACC) is a slow growing, but relentless cancer. Due to its rarity and lack of understanding of its molecular etiology, no standard chemotherapy for ACC currently exists and many patients suffer from recurrent and/or metastatic disease. As such, development of safe and effective therapies is imperative. To describe and summarize existing clinical trial studies and preclinical discoveries, we surveyed the PubMed on developmental therapeutics for ACC. Objective response rates to monotherapy with cytotoxic agents were approximately 10% with cisplatin, 5-FU, gemcitabine, mitoxantrone, epirubicin, vinorelbine and paclitaxel. The most studied combination therapies were cyclophosphamide-doxorubicin-cisplatin (CAP) and cisplatin-vinorelbine, with an objective response rate of 18-31%. Among molecularly targeted drugs, the most studied drugs are inhibitors targeting the vascular endothelial growth factor receptor (VEGFR) to inhibit tumor angiogenesis. Among those, lenvatinib and axitinib showed a relatively high objective response rate of 11-16% and 9-17%, respectively. Given high recurrence rates and chemoresistance of ACC, treatments targeting cancer stem cells (CSC), which function as tumor-initiating cells and drive chemoresistance, may be particularly valuable. CSC have been shown to be targetable via MYB, Notch1, p53 and epigenetic mechanisms. Myb overexpression is characteristic in ACC but was previously thought to present a difficult target due to its nature as a transcription factor. However, due to the development Myb-targeted inhibitors and an ongoing clinical trial of MYB-targeted cancer vaccine therapy, MYB is becoming an increasingly attractive therapeutic target. Drugs targeting NOTCH signaling demonstrated 5-17% response rate in phase I clinical trials. Within the field of epigenetics, treatment with PRMT5 inhibitors has shown 21% partial response rate in phase I clinical trial. Immunotherapies, such as PD-1 inhibitors, are also associated with CSC, but have not been effective against ACC. However, clinical trials of cancer vaccine therapies are actively being conducted. In addition to conventional chemotherapies and inhibitors of angiogenesis, the emergence of new therapies such as immunotherapy and those targeting cancer stemness is expected to bring clinical benefits to patients in the future.

Dataset Information

Inhibition of survivin reduces HIF-1?, TGF-?1 and TFE3 in salivary adenoid cystic carcinoma.

Publications

Inhibition of survivin reduces HIF-1α, TGF-β1 and TFE3 in salivary adenoid cystic carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets