Abstract:
Background:Several intracellular signaling pathways that are deregulated during hepatocarcinogenesis might constitute potential targets for hepatocellular carcinoma (HCC) therapy. The aim of this study was to test the potential synergic antitumor effect of salirasib and sorafenib in a diethylnitrosamine (DEN)-induced HCC model in rat. The hypothesis of tumor phenotype changes during treatment was also analyzed. Materials and methods:DEN was administered to Wistar rats during 9 weeks to induce cirrhosis and liver cancer. After tumor development, rats were treated with intraperitoneal injections of dimethyl sulfoxide (DMSO), or salirasib, and/or with oral sorafenib 5 days/week, during 4 weeks. At sacrifice, number and size of liver tumors as well as tumor burden were recorded, and all liver tumors were processed for histological and immunohistological analyses. Results:Mortality rate was significantly higher in rats treated with salirasib and/or sorafenib than in the control group (P=0.001). Tumor burden was smaller in the treated group compared with the DMSO control group (P=0.044), but a synergistic effect of the two chemotherapies could not be observed. In 62.5% of rats (10/16) treated with salirasib and/or sorafenib, a cytokeratin-7 and -19-positive hepatocholangiocellular carcinoma (HCC/CHC) was found vs 20% (5/25) developing such phenotype in the DMSO control group (P=0.018). Ki67 immunostaining showed significantly reduced tumor cell proliferation in treated rats (P=0.001), whereas apoptosis as assessed by caspase-3 activity in cell lysate was similar in all groups. Conclusions:The addition of sorafenib to salirasib did not seem to provide any synergistic therapeutic effect in this study. Both chemotherapeutic agents, administered alone or in combination, induced tumoral phenotypic changes in the majority of rats, a finding not associated with an increased tumor cell proliferation or decreased apoptosis. The rat model described in this work constitutes the first experimental tool generating putatively more aggressive combined HCC/CHC tumors following chemotherapy. Further work is required to better characterize this clinically relevant phenomenon.
journal_name
Onco Targets Therjournal_title
OncoTargets and therapyauthors
Ciccarelli O,Colson A,De Saeger C,Reding R,Sempoux C,Leclercq IA,Stärkel Pdoi
10.2147/OTT.S176903subject
Has Abstractpub_date
2018-10-17 00:00:00pages
7143-7153issn
1178-6930pii
ott-11-7143journal_volume
11pub_type
杂志文章abstract::Discovered in 2007, anaplastic lymphoma kinase (ALK) gene rearrangements positive (ALK+) lung cancers compose a small subset of non-small cell lung cancer (NSCLC), with rapidly expanded treatments. There are currently several ALK inhibitors, including crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib which ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S174548
更新日期:2019-06-13 00:00:00
abstract:Aim:To explore the expression and clinical significance of long noncoding RNA (lncRNA) gastric cancer-associated transcript 3 (GACAT3) in human colorectal cancer (CRC). Methods:Expression of GACAT3 in CRC tissues and cell lines was measured using quantitative real-time PCR. CCK-8 and colony formation assays were used ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S144103
更新日期:2018-03-19 00:00:00
abstract:Background:Despite the breadth of understanding the noncoding RNAs' function in molecular biology, their functional roles in hepatocellular carcinoma (HCC) is poorly understood. In this study, we investigated the effect of hepatitis C virus (HCV) core upon the expression of noncoding RNAs. Methods:The lncRNAs, mRNAs, ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S149254
更新日期:2018-03-02 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
pub_type: 杂志文章
doi:10.2147/OTT.S200755
更新日期:2019-05-31 00:00:00
abstract:Objective:This study aimed to evaluate the safety and efficacy of intensity-modulated radiotherapy (IMRT) plus nimotuzumab with or without concurrent chemotherapy (CCT) for patients with locally advanced nasopharyngeal carcinoma (LA-NPC). Patients and methods:A total of 50 newly diagnosed patients with LA-NPC treated ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S151554
更新日期:2017-12-08 00:00:00
abstract:Background:Nasopharyngeal carcinoma (NPC) is a common malignant cancer that is distributed particularly in Southeastern Asia. Previous studies have manifested that long noncoding RNA urothelial carcinoma associated 1 (UCA1) was involved in NPC tumorigenesis and metastasis. However, the biological mechanism of UCA1 for ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S215819
更新日期:2019-10-11 00:00:00
abstract:PURPOSE:The prognostic significance of circulating tumor cells (CTCs) in esophageal carcinoma (EC) is controversial. We aim to assess its association with clinicopathological and prognostic relevance in EC by using a meta-analysis. METHODS:We searched PubMed, Cochrane Database, Embase databases, and the references in ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S100005
更新日期:2016-03-31 00:00:00
abstract::Ewing's sarcoma is a rare and highly aggressive cancer most frequently arising in people under 20 years of age. We report an uncommon case of primary paraesophageal Ewing's sarcoma in a 25-year-old male harboring the infrequent EWSR1/ERG fusion transcript with multiple splice variants coexisting in the same tumor. The...
journal_title:OncoTargets and therapy
pub_type:
doi:10.2147/OTT.S80879
更新日期:2015-05-14 00:00:00
abstract::Immune cells are essential for defending the body's balance and have increasingly been implicated in controlling tumor growth. In cervical cancer (CC), the immune landscape is extensively connected with human papillomavirus (HPV) status. Recent insights from studies have revealed that as a result of infection with HPV...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S264312
更新日期:2020-08-12 00:00:00
abstract:Purpose:Traditional Chinese medicine (TCM) has gained increasing attention for the treatment of multiple chronic diseases, such as cancer. Here we aim to identify the antitumor activity of Sichong formula, a novel TCM, in human gastric cancer cells and investigate the underlying mechanisms. Methods:The AGS and MKN45 g...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S199605
更新日期:2019-07-16 00:00:00
abstract::The mitogen-activated protein kinase (MAPK) pathway is a critical oncogenic driver signal in a number of malignancies. The discovery of activating mutations in the MAPK pathway has led to the development of MAPK pathway inhibitors. Selumetinib is a potent and selective inhibitor of MEK1 and MEK2, which are essential d...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S51596
更新日期:2014-09-19 00:00:00
abstract::Angiogenesis plays an essential role in the development of most solid tumors by delivering nutrients and oxygen to the tumor. Therefore, anti-angiogenic therapy, particularly anti-VEGF and anti-VEGF receptor (VEGFR) therapy, has been a popular strategy to treat cancer. However, anti-angiogenic therapy does not signifi...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S276150
更新日期:2020-11-24 00:00:00
abstract:Background:The global Phase III LUX-Lung 8 trial (ClinicalTrials.gov: NCT01523587) identified significant improvements in progression-free survival (PFS), overall survival (OS), and patient-reported outcomes (PROs) with second-line afatinib vs erlotinib in patients with advanced squamous cell carcinoma (SCC) of the lun...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S161506
更新日期:2018-11-30 00:00:00
abstract:Background:Sex-determining region Y-box protein 5 (SOX5) has been demonstrated to be implicated in oncogenic function in various types of cancers. However, the role of SOX5 in gastric cancer (GC) remains poorly elucidated. Herein, we investigated the role and the underlying mechanism of SOX5 in GC progression. Methods...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S197087
更新日期:2019-04-03 00:00:00
abstract:Objective:This study aims to uncover the progression of thyroid carcinoma influenced by the m6A methyltransferase METTL3 through regulating m6A methylation on TCF1 mRNA and the activated Wnt pathway. Methods:Thyroid carcinoma tissues and paracancerous ones were collected for detecting levels of METTL3 and TCF1. Potent...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S234751
更新日期:2020-02-21 00:00:00
abstract::Purpose: Wolf-Hirschhorn syndrome candidate 1 (WHSC1) is an epigenetic modifier, considered to play a driving role in oncogenesis. However, very little is known about the roles of WHSC1 and its prognostic impacts in cervical cancer. This study aimed to investigate the role of WHSC1 in the prognosis of cervical cancer ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S204701
更新日期:2019-06-17 00:00:00
abstract:BACKGROUND:Breast cancer is one of the most frequently occurring cancers in women. In recent years, Dendrobium candidum has played a part in antihyperthyroidism and anticancer drugs. This study aims to examine the antitumor effect of D. candidum on breast cancer. METHODS:Human breast cancer cell line MCF-7 and normal ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S93305
更新日期:2015-12-21 00:00:00
abstract:BACKGROUND:Experimental disruption of the telomere overhang induces a potent DNA damage response and is the target of newly emerging cancer therapeutics. Introduction of T-oligo, an eleven-base oligonucleotide homologous to the 3'-telomeric overhang, mimics telomere disruption and induces DNA damage responses through a...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S54575
更新日期:2013-12-18 00:00:00
abstract:BACKGROUND:In patients with gastric cancer (GC), survival is poor, given the late diagnosis. Risk-stratifying these patients earlier could help improve care. We determined whether combining preoperative albumin concentration and the neutrophil lymphocyte ratio (COA-NLR) could predict overall survival (OS) better than o...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S108631
更新日期:2016-07-27 00:00:00
abstract::Prostate cancer is the leading malignancy and the second most common cause of cancer-related death in men. Despite high cure rates with surgery and/or radiation, 30%-40% of patients eventually develop advanced cancer. Docetaxel is one of the most effective and well established chemotherapeutic agents for prostate canc...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S79105
更新日期:2015-04-10 00:00:00
abstract::p125 is one of four subunits of human DNA polymerases - DNA Pol δ as well as one of p53 target protein encoded by POLD1. However, the function and significance of p125 and the role that p53 plays in regulating p125 expression are not fully understood in breast cancer. Tissue sections of human breast cancer obtained fr...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S98713
更新日期:2016-03-10 00:00:00
abstract:BACKGROUND:Recent studies show that epithelial-mesenchymal transition (EMT) and tumor-associated macrophages (TAMs) contribute to the progression and poor prognosis of carcinoma through multiple mechanisms. Both inflammation and changing of epithelium have a close relationship with tumorigenesis of gastric cancer. Howe...
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::Recently, the human gene NOTCH1 has been found to be implicated in cancer cell metastasis and the maintenance of cancer stem cells. However, for breast cancer in particular, an association between NOTCH1 levels and metastasis has not been determined. In this study, we investigated the expression status and correlation...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S109606
更新日期:2016-11-07 00:00:00
abstract:BACKGROUND:Recurrent laryngeal nerve (RLN) invasion in papillary thyroid carcinoma (PTC) is one of the main predictors of poor prognosis. The present study investigated the risk factors for RLN invasion in PTC patients. METHODS:A total of 3,236 patients who received thyroidectomy due to PTC in Thyroid and Parathyroid ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S142799
更新日期:2017-09-11 00:00:00
abstract::Gastrointestinal stromal tumor (GIST) is an uncommon mesenchymal tumor, and has been shown to be associated with synchronous or metachronous second malignancies. Rare cases of coincident GIST and non-Hodgkin lymphomas (NHL) have been reported previously. Here, we report two cases of GIST and coincident primary breast ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S159843
更新日期:2018-12-10 00:00:00
abstract::This retrospective study was conducted to evaluate the prognostic significance of the preoperative plasma D-dimer levels and platelet counts in patients with pancreatic adenocarcinoma. A total of 168 consecutive locally advanced pancreatic adenocarcinoma patients who underwent intensity modulated radiation therapy wit...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S82329
更新日期:2015-06-04 00:00:00
abstract:PURPOSE:We validated the use of expression sequence tags (ESTs) as an effective method of screening for DNA segments that could predict urothelial cell carcinoma and for identifying ESTs with such predictive value. PATIENTS AND METHODS:From 2004 to 2009, eleven patients were enrolled in this study: six with high-grade...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S69239
更新日期:2014-09-30 00:00:00
abstract::The identification of molecular genetic biomarkers considerably increased our current understanding of glioma genesis, prognostic evaluation, and treatment planning. In glioblastoma, the most malignant intrinsic brain tumor entity in adults, the promoter methylation status of the gene encoding for the repair enzyme O6...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S50208
更新日期:2013-09-27 00:00:00
abstract::Medullary thyroid carcinoma (MTC) is a rare malignancy originating from calcitonin-producing parafollicular C cells of the thyroid. Neither radiotherapy nor chemotherapy has demonstrated durable objective responses in patients with advanced MTC. Vandetanib and cabozantinib are the 2 tyrosine kinase inhibitors recently...
journal_title:OncoTargets and therapy
pub_type:
doi:10.2147/OTT.S142598
更新日期:2018-01-19 00:00:00
abstract::Large granular lymphocytic leukemia (LGLL) is a rare lymphoproliferative disorder of transformed natural killer or T-cells attributed to chronic exposure to the proinflammatory cytokine IL-15. Diagnosis of the majority of T-cell LGLL is established by documenting clonal large granular lymphocytes (LGLs) in peripheral ...
journal_title:OncoTargets and therapy
pub_type:
doi:10.2147/OTT.S115892
更新日期:2016-12-19 00:00:00