Abstract:
BACKGROUND:Gallbladder carcinoma is a highly malignant tumor and a public health problem in some parts of the world. It is characterized by a poor prognosis and its resistance to radio and chemotherapy. There is an urgent need to develop novel therapeutic alternatives for the treatment of gallbladder carcinoma. The mammalian target of the rapamycin (mTOR) signaling pathway is activated in about 50% of human malignancies, and its role in gallbladder carcinoma has previously been suggested. In the present study, we investigated the phosphorylation status of the mTOR substrate p70S6K in preneoplastic and neoplastic gallbladder tissues and evaluated the effect of three mTOR inhibitors on cell growth and migration in gallbladder carcinoma cell lines. METHODS:Immunohistochemical staining of phospho-p70S6K was analyzed in 181 gallbladder carcinoma cases, classified according to lesion type as dysplasia, early carcinoma, or advanced carcinoma. Protein expression of AKT/mTOR members was also evaluated in eight gallbladder carcinoma cell lines by Western blot analysis. We selected two gallbladder carcinoma cell lines (G415 and TGBC-2TKB) to evaluate the effect of rapamycin, RAD001, and AZD8055 on cell viability, cell migration, and protein expression. RESULTS:Our results showed that phospho-p70S6K is highly expressed in dysplasia (66.7%, 12/18), early cancer (84.6%, 22/26), and advanced cancer (88.3%, 121/137). No statistical correlation was observed between phospho-p70S6K status and any clinical or pathological features, including age, gender, ethnicity, wall infiltration level, or histological differentiation (P < 0.05). In vitro treatment with rapamycin, RAD001, and AZD8055 reduced cell growth, cell migration, and phospho-p70S6K expression significantly in G-415 and TGBC-2TKB cancer cells (P < 0.001). CONCLUSION:Our findings confirm the upregulation of this signaling pathway in gallbladder carcinoma and provide a rationale for the potential use of mTOR inhibitors as a therapeutic strategy for human gallbladder carcinoma.
journal_name
Onco Targets Therjournal_title
OncoTargets and therapyauthors
Leal P,Garcia P,Sandoval A,Buchegger K,Weber H,Tapia O,Roa JCdoi
10.2147/OTT.S46897subject
Has Abstractpub_date
2013-10-03 00:00:00pages
1373-84issn
1178-6930pii
ott-6-1373journal_volume
6pub_type
杂志文章abstract::Huaier (Trametes robiniophila Murr), a Chinese traditional herb of medicine, has demonstrated promising curative effects in clinical treatment for various tumors. There are documented experiments showing the biological functions of Huaier with its antineoplastic molecular mechanisms: restraining proliferation and meta...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S281328
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abstract:Background:Nicotinamide phosphoribosyltransferase (NAMPT) and the transforming growth factor-β (TGF-β) signaling pathway play important roles in colorectal tumorigenesis and progress. However, the underlying regulatory mechanisms between NAMPT and TGF-β signaling in colorectal cancer (CRC) remain poorly understood. Me...
journal_title:OncoTargets and therapy
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journal_title:OncoTargets and therapy
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journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S159777
更新日期:2018-05-28 00:00:00
abstract:Background:The aim of this study was to investigate the correlation of EGFR mutation on the high-resolution computed tomography (HRCT) features in lung adenocarcinoma. Patients and methods:A total of 121 patients were diagnosed with lung adenocarcinoma from January 2014 to December 2016. The correlation of indexes (ge...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S184217
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abstract::Trastuzumab is a monoclonal antibody directed against the human epidermal growth factor receptor 2 (HER2). HER2 is amplified or overexpressed in about 15% of breast cancers and is associated with aggressive disease. Clinical benefits of trastuzumab have been established in the treatment of both early and metastatic HE...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S27733
更新日期:2013-01-01 00:00:00
abstract::Background: Circ-SHPRH is a novel circular RNA which was down-regulated in various cancer tissues. Several recent studies hinted that circ-SHPRH might function as a diagnostic and prognostic biomarker for solid cancers. This meta-analysis was performed to determine the diagnostic and prognostic roles of circ-SHPRH for...
journal_title:OncoTargets and therapy
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doi:10.2147/OTT.S200755
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abstract:Background and aim:Standard chemotherapy has limited clinical efficacy in patients with esophageal cancer and there is a significant and unmet clinical need for effective treatment options for these patients. The aim of this study was to compare the clinical efficacy of the novel, targeted drug apatinib combined with d...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S191736
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abstract:Purpose:Although cisplatin-based adjuvant chemotherapy improves the survival of patients with resected non-small-cell lung cancer, not all patients show a survival benefit, and some patients experience severe toxicity. Therefore, identifying biomarkers is important for selecting subgroups of patients who may show impro...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S145072
更新日期:2017-11-02 00:00:00
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journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S176388
更新日期:2018-10-09 00:00:00
abstract::Giant-cell carcinoma of the lung (GCCL) is a rare histological form of poorly differentiated non-small-cell lung cancer, which is classified as a subtype of pulmonary sarcomatoid carcinomas. In this case report, we describe the case of a 50-year-old Chinese male who presented with a pulmonary nodule in the right upper...
journal_title:OncoTargets and therapy
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doi:10.2147/OTT.S150124
更新日期:2018-02-09 00:00:00
abstract:Background:Breast cancer resistance protein BCRP, belonging to superfamily G of the adenosine triphosphate-binding cassette (ABC) transporters, is an efflux pump and plays a critical role in protecting cells against xenobiotics and toxic compounds including (pro)carcinogens. BCRP is expressed in many tissues, including...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S195245
更新日期:2019-02-27 00:00:00
abstract:Purpose:Circulating tumor DNA (ctDNA) is a noninvasive and real-time marker for tumor diagnosis, prognosis, and prediction. However, further investigations about ctDNA prognostic and predictive value are still needed, and conclusions from several studies were inconsistent. Experimental design:We performed capture-base...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S154589
更新日期:2018-01-12 00:00:00
abstract:Objective:Osteoclastogenesis is a key process in osteolytic bone metastasis (BM). Previous studies indicated that some miRNAs could regulate cancers progression and osteoclastogenesis. Our purpose was to investigate the roles of lung cancer cells-derived circulating miR-21 on osteoclastogenesis and its clinical signifi...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S232876
更新日期:2020-03-31 00:00:00
abstract:Purpose:The aim of this study was to investigate the antitumor effect of chidamide in combination with bortezomib on gastric cancer cell lines. Materials and Methods:First, the sensitivity and IC50 values of chidamide and bortezomib in several gastric cancer cell lines (MGC-803, BGC-823, SGC-7901, and MKN45) were meas...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S240721
更新日期:2020-05-06 00:00:00
abstract::Quercetin is proven to have anticancer effects for many cancers. However, the role of tumor suppressor p53 on quercetin's radiosensitization and regulation of endoplasmic reticulum (ER) stress response in this process remains obscure. Here, quercetin exposure resulted in ER stress, prolonged DNA repair, and the expres...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S147316
更新日期:2017-12-21 00:00:00
abstract:Background:With the purpose of elevating the risk of cholangiocarcinoma (CCA), alcoholic liver disease (ALD) was shown. Nonetheless, the findings were controversial. Herein, a meta-analysis and a systematic review were conducted to study the relation as mentioned above. Methods:This study searched PubMed, EMBASE, and ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S184444
更新日期:2018-11-20 00:00:00
abstract:Purposes:The main aim of the study was to investigate the dosimetric difference between acuros XB algorithm (AXB), anisotropic analytic algorithm (AAA), and pencil beam convolution (PBC) algorithm in stereotactic body radiation therapy (SBRT) plan for non-small cell lung cancer (NSCLC). Patients and Methods:Thirty-eig...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S201473
更新日期:2019-08-12 00:00:00
abstract:Objective:The objective of this study was to investigate the safety of robotic stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) patients and its related factors. Methods:A total of 74 HCC patients with Child-Turcotte-Pugh (CTP) Class A were included in a multi-institutional, single-arm Pha...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S142025
更新日期:2017-11-06 00:00:00
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journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S86093
更新日期:2015-09-18 00:00:00
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journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S145473
更新日期:2018-03-23 00:00:00
abstract::Defects in the innate immune system, particularly in Toll-like receptors (TLRs), have been reported in several cigarette smoke-promoted diseases. The aim of this study was to examine the impact of tobacco smoke on allelic frequencies of TLR4 single-nucleotide polymorphisms (SNPs) and to compare the genotypic distribut...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S111971
更新日期:2017-02-09 00:00:00
abstract:Purpose:This study aimed to investigate the regulatory roles of estrogen receptor beta (ERβ) on gastric cancer (GC) cells, and reveal the potential mechanisms relating to nuclear factor-kappa B (NF-κB) signaling. Methods:GC cell lines SGC7901 and MKN45 were transfected with pEGFP-C1-ERβ to overexpress ERβ, and treated...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,收录出版
doi:10.2147/OTT.S214529
更新日期:2019-11-05 00:00:00
abstract:Background/aim:Urothelial bladder cancer arises from the accumulation of multiple epigenetic and genetic changes. We aimed to investigate the specificity and sensitivity of gene-specific promoter methylation of CDH1 and p14ARF genes in the early diagnosis of bladder cancer and compare those with other diagnostic tests ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S158259
更新日期:2018-07-19 00:00:00
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journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S103112
更新日期:2016-06-30 00:00:00
abstract::Lung cancer has the highest morbidity and mortality in the world, and non-small cell lung carcinomas (NSCLC) account for 80% of cases of lung cancer. The mechanism of NSCLC is still largely unknown, and finding novel targets is of great importance for the treatment of NSCLC. The current study was designed to evaluate ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S123518
更新日期:2017-03-02 00:00:00
abstract::To date, 10 years after the first demonstration of circulating tumor cells (CTCs), prognostic significance in metastatic breast cancer using the US Food and Drug Administration-cleared system CellSearch(®), the potential utility of CTCs in early clinical development of drugs, their role as a surrogate marker of respon...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S46200
更新日期:2014-04-17 00:00:00
abstract:Objective:The role of neoadjuvant therapy (NAT) in resectable pancreatic cancer (RPC) remains controversial. Therefore, this meta-analysis was performed to compare the clinical differences between NAT and upfront surgery in RPC. Materials and methods:A systematic literature search was performed in PubMed, Embase, Web ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S190810
更新日期:2019-01-22 00:00:00
abstract:Background:Lung cancer is one of the most common malignancies in the world and is at the forefront of causes of all cancer deaths. Identification of new prognostic predictors or therapeutic targets might improve a patient's survival rate. Purpose:The Homeodomain interacting protein kinases (HIPKs) function as modulato...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S166878
更新日期:2018-10-25 00:00:00
abstract::Gastric cancer (GC) is one of the leading causes of tumor-related mortality. In addition to surgery and endoscopic resection, systemic therapy remains the main treatment option for GC, especially for advanced-stage disease and for cases not suitable for surgical therapy. Hence, improving the efficacy of systemic thera...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S221354
更新日期:2019-12-24 00:00:00