Abstract:
BACKGROUND:Increased expression of epidermal growth factor receptor (EGFR) and its ligands is associated with poor prognosis and chemoresistance in many carcinoma types, but its role in head and neck squamous cell carcinoma (HNSCC) is unclear. Our aim was to clarify whether mRNA expression of EGFR-ligands was linked to prognosis and cisplatin resistance, and if so, which ligand was most important and how was the expression regulated. METHODS:To examine the prognostic effect of EGFR-ligand expression, we analyzed tumorous mRNA expression in 399 HNSCC patients. The intracellular signaling pathways controlling epidermal growth factor (EGF)-induced amphiregulin (AREG) expression were examined in three oral squamous cell carcinoma (OSCC) cell lines. Effect of AREG on cisplatin resistance was examined by viability assays in four-, and by association in 11 OSCC cell lines. RESULTS:The patients were divided into five groups according to the median mRNA expression levels of four EGFR ligands, i.e. AREG, EGF, heparin-binding EGF-like growth factor (HBEGF) and beta-cellulin (BTC). The number of increased-expressed EGFR-ligands were progressively correlated to five-year survival, even in advanced TNM-stage IV patients, where five-year mortality increased from 26 % if tumor expressed none to one EGFR-ligand, to 45 % in three to four ligand expressing tumors. Thus, staging the tumor according to these EGFR-ligand mRNA expression pattern completely out performed TNM staging in predicting prognosis. Multivariate analysis identified AREG as the dominating predictor, and AREG was overexpressed in OSCC compared to tumors from other sites. Both EGF and HBEGF stimulation induced strong AREG increase in OSCC cell lines, which was partially mediated by the extracellular signal-regulated kinase 1/2 pathway, and negatively regulated by p38, c-Jun N-terminal kinase, and phosphoinositide-3 kinase. Although increased AREG mRNA expression predicted unfavorable prognosis in platinum treated HNSCC patients, AREG did not mediate cisplatin resistance in the OSCC cell lines. CONCLUSIONS:Increased tumorous mRNA expression of four EGFR ligands was progressively associated with poor prognosis in HNSCC. Thus, EGFR-ligands mRNA expression pattern may be a new prognostic biomarker. The tightly regulated EGF-induced AREG mRNA expression was partly lost in the OSCC cell lines and restoring its regulation may be a new target in cancer treatment. TRIAL REGISTRATION:Not applicable as the clinical data of the 498 HNSCC patients and their mRNA expression profiles were collected from the open TCGA database: http://cancergenome.nih.gov/cancersselected/headandneck .
journal_name
J Exp Clin Cancer Resjournal_title
Journal of experimental & clinical cancer research : CRauthors
Gao J,Ulekleiv CH,Halstensen TSdoi
10.1186/s13046-016-0422-zsubject
Has Abstractpub_date
2016-09-26 00:00:00pages
151issue
1eissn
0392-9078issn
1756-9966pii
10.1186/s13046-016-0422-zjournal_volume
35pub_type
杂志文章abstract:BACKGROUND:Increasing evidence highlights the important roles of tripartite motif containing 24 (TRIM24) in tumor initiation and malignant progression in many tumors, including gastric cancer (GC). Although TRIM24 expression is remarkably upregulated during GC carcinogenesis, the molecular mechanisms underlying TRIM24 ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-017-0489-1
更新日期:2017-01-23 00:00:00
abstract:BACKGROUND:Immunocytochemistry and RT-PCR have been widely used for the detection of circulating tumor cells in patients with breast cancer but their specificity is limited. Our purpose is to utilize a convenient and specific technology to detect circulating tumor cells in breast cancer patients. METHODS:To determine ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-28-57
更新日期:2009-04-28 00:00:00
abstract:BACKGROUND:Localized C3 deposition is a well-known factor of inflammation. However, its role in oncoprogression of gastric cancer (GC) remains obscured. This study aims to explore the prognostic value of C3 deposition and to elucidate the mechanism of C3-related oncoprogression for GC. METHODS:From August to December ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 临床试验,杂志文章
doi:10.1186/s13046-019-1514-3
更新日期:2020-01-13 00:00:00
abstract:BACKGROUND:Antibody Directed Enzyme Prodrug Therapy (ADEPT) can be used to generate cytotoxic agents at the tumor site. To date non-human enzymes have mainly been utilized in ADEPT. However, these non-human enzymes are immunogenic limiting the number of times that ADEPT can be administered. To overcome the problem of i...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-28-147
更新日期:2009-12-03 00:00:00
abstract:BACKGROUND:Esophageal squamous cell carcinoma (ESCC) is an aggressive tumor with dismal prognosis and high incidence and mortality in Kazakh population. MiR-34a, a direct p53 target gene, possesses tumor-suppressive properties as they mediate apoptosis, cell cycle arrest, and senescence. The reduced expression of miR-3...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-33-20
更新日期:2014-02-17 00:00:00
abstract:BACKGROUND:In this research, we aimed to resolve contradictory results whether SOX9 plays a positive or negative role in melanoma progression and determine whether SOX9 and its closely related member SOX10 share the same or distinct targets in mediating their functions in melanoma. METHODS:Immunofluorescence, TCGA dat...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-018-0998-6
更新日期:2019-01-14 00:00:00
abstract:BACKGROUND:Celastrol, a triterpene compound derived from the traditional Chinese medicine Tripterygium wilfordii, has been reported to possess potential antitumor activity towards various malignancies. However, the effect of celastrol on glioma cells and the underlying molecular mechanisms remain elusive. METHODS:Glio...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1173-4
更新日期:2019-05-03 00:00:00
abstract::Gastric tissue was transplanted from the fundic and pyloric mucosa of 8-week old female F344 rats into the duodenum of males. Autopsy, 12 months after the operation, revealed grafts associated with persistent stones in the duodenum and/or calcification in the tissue. Pepsinogen positive chimeric glands with goblet cel...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2000-06-01 00:00:00
abstract:BACKGROUND:Anti-angiogenesis remains an attractive strategy for cancer therapy. Some anti-angiogenic reagents have bell-shape dose-response curves with higher than the effective doses yielding lower anti-angiogenic effects. In this study, two different types of anti-angiogenic reagents, a receptor tyrosine kinase inhib...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,收录出版
doi:10.1186/s13046-019-1324-7
更新日期:2019-08-28 00:00:00
abstract::Tumor-infiltrating immune cells play a key role against cancer. However, malignant cells are able to evade the immune response and establish a very complex balance in which different immune subtypes may drive tumor progression, metastatization and resistance to therapy. New immunotherapeutic approaches aim at restorin...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:10.1186/s13046-020-01586-y
更新日期:2020-05-18 00:00:00
abstract:UNLABELLED:PCR analysis has been demonstrated as a valuable tool for detection of minimal residual disease (MRD) in lymphoid malignancies. However, the finding that patients with evidence of MRD sometimes remain in long-lasting remission directs further investigations toward biology of residual disease and/or quantific...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2007-12-01 00:00:00
abstract::The recent studies have evaluated the relationship between BRCA1 expression and clinical outcome of chemotherapy (mainly focused on platinum-based and toxal-based treatment) in NSCLC patients, but the results were inconclusive and controversial. Our aim of this study was to evaluate this association by literature base...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,meta分析,评审
doi:10.1186/1756-9966-32-15
更新日期:2013-03-15 00:00:00
abstract::We report a case of a 72-year-old male, with a known history of non-Hodgkin lymphoma of the left tonsil for two years, histologically proved and successfully treated by radical surgical excision in combination with external radiotherapy. He presented with diffuse bone pain the last month, especially at the lower left ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2002-09-01 00:00:00
abstract:BACKGROUND:An increasing number of studies have shown that long noncoding RNAs (lncRNAs) play essential roles in tumor initiation and progression. LncRNAs act as tumor promoters or suppressors by targeting specific genes via epigenetic modifications and competing endogenous RNA (ceRNA) mechanisms. In this study, we exp...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1421-7
更新日期:2019-10-17 00:00:00
abstract::In the original publication of this manuscript [1], Fig. 1 contained a typographical error ('Metabolic' incorrectly written as 'Metabolig'). ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 已发布勘误
doi:10.1186/s13046-020-1532-1
更新日期:2020-02-24 00:00:00
abstract::A single guanine insertion (1G/2G polymorphism) in the promoter of the matrix metalloproteinase (MMP-1) gene creates a binding site for the transcription factor and may affect the level of transcription of MMP-1. An elevated level of MMP-1 in cancer cells may facilitate their invasion and contribute to metastasis. To ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2004-03-01 00:00:00
abstract:BACKGROUND:The human epidermal growth factor receptor 2 (HER2) and p53 pathways may be involved in chemotherapy sensitivity and/or resistance. We explore the value of HER2 and p53 status to foretell docetaxel sensitivity in advanced breast cancer. METHODS:HER2 and p53 expression was analysed in 36 (median age 55 yrs; ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-30-38
更新日期:2011-04-11 00:00:00
abstract::Screening for ovarian cancer is an important step in improving ovarian cancer mortality. This is a report of screening for ovarian cancer using transvaginal sonography (TVS) on 2,095 asymptomatic women during the past four years. Ovarian tumors over 30 mm in diameter were detected in 87 women (4.2%). Fourteen tumors w...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:1997-06-01 00:00:00
abstract::Hepatocellular carcinoma (HCC) ranks the most common primary liver malignancy and the third leading cause of tumor-related mortality worldwide. Unfortunately, despite advances in HCC treatment, less than 40% of HCC patients are eligible for potentially curative therapies. Recently, cancer immunotherapy has emerged as ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:10.1186/s13046-019-1396-4
更新日期:2019-09-09 00:00:00
abstract:BACKGROUND:Yes-associated protein (YAP), an essential component of Hippo pathway, was identified as an oncoprotein which participated in the progression of various malignancies. However, its role in chronic myeloid leukemia (CML) remains to be further clarified. METHODS:The expression of YAP in CML cells was determine...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-016-0414-z
更新日期:2016-09-06 00:00:00
abstract:BACKGROUND:Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of tumors, with aggressive clinical course that renders prognostication and choice of treatment strategy difficult. Chemo-immunotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) is the current first-line trea...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-018-0768-5
更新日期:2018-05-02 00:00:00
abstract::The present study assesses the adaptation of a group of female patients with either manifest or suspected breast cancer who have undergone Magnetic Resonance Imaging (MRI) after receiving psychological support. Several studies in literature have reported the effectiveness of such support in reducing anti-oxidant and d...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2006-12-01 00:00:00
abstract:BACKGROUND:One-third of estrogen (ER+) and/or progesterone receptor-positive (PGR+) breast tumors treated with Tamoxifen (TAM) do not respond to initial treatment, and the remaining 70% are at risk to relapse in the future. Estrogen-related receptor gamma (ESRRG, ERRγ) is an orphan nuclear receptor with broad, structur...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-015-0150-9
更新日期:2015-05-15 00:00:00
abstract:BACKGROUND:Parallel to complex alteration in molecular and cellular events, enrichment of cancer stem cells (CSC) contributes significantly in deliberation and maintenance of cisplatin resistance. Cisplatin mediated CSC enrichment is well established in various cancers, yet the underlying mechanism is largely unknown. ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-017-0636-8
更新日期:2017-11-23 00:00:00
abstract:BACKGROUND:Recently, leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1), a negative regulator of EGFR, was discovered is a novel agent for suppressing bladder cancer. The aim of this study was to investigate the impact of LRIG1 on the biological features of aggressive bladder cancer cells and the possible m...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-32-101
更新日期:2013-12-08 00:00:00
abstract:BACKGROUND:The epithelial-to-mesenchymal transition (EMT) accompanied by the downregulation of E-cadherin has been thought to promote metastasis. Cyclooxygenase-2 (Cox-2) is presumed to contribute to cancer progression through its multifaceted function, and recently its inverse relationship with E-cadherin was suggeste...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-33-40
更新日期:2014-05-10 00:00:00
abstract:BACKGROUND:An External Quality Assessment (EQA) program was developed to investigate the state of the art of HER2 immunohistochemical determination in breast cancer (BC) in 16 Pathology Departments in the Lazio Region (Italy). This program was implemented through two specific steps to evaluate HER2 staining (step 1) an...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-32-58
更新日期:2013-08-21 00:00:00
abstract::The aim of this study was to assess the efficiency of the radioguided localization and excision technique using radiopharmaceuticals injected directly or close to occult breast lesions. We studied thirty-two consecutive patients with thirty-six occult breast lesions detected mammographically or ultrasonically categori...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 临床试验,杂志文章
doi:
更新日期:2007-09-01 00:00:00
abstract:BACKGROUND:Anti-angiogenic therapies demonstrate anti-tumor effects by decreasing blood supply to tumors and inhibiting tumor growth. However, anti-angiogenic therapy may leads to changes in tumor microenvironment and increased invasiveness of tumor cells, which in turn promotes distant metastasis and increased drug re...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1291-z
更新日期:2019-07-02 00:00:00
abstract:BACKGROUND:Macroautophagy (hereafter referred to as autophagy) is an evolutionarily conserved intracellular mechanism for lysosomal degradation of damaged cellular components. The specific degradation of nuclear components by the autophagy pathway is called nucleophagy. Most studies have focused on autophagic turnover ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1048-8
更新日期:2019-02-11 00:00:00