Abstract:
BACKGROUND:Advanced biliary tract carcinomas (BTCs) have poor prognosis and limited therapeutic options. Therefore, it is crucial to combine standard therapies with molecular targeting. In this study EGFR, HER2, and their molecular transducers were analysed in terms of mutations, amplifications and over-expression in a BTC case series. Furthermore, we tested the efficacy of drugs targeting these molecules, as single agents or in combination with gemcitabine, the standard therapeutic agent against BTC. METHODS:Immunohistochemistry, FISH and mutational analysis were performed on 49 BTC samples of intrahepatic (ICCs), extrahepatic (ECCs), and gallbladder (GBCs) origin. The effect on cell proliferation of different EGFR/HER2 pathway inhibitors as single agents or in combination with gemcitabine was investigated on BTC cell lines. Western blot analyses were performed to investigate molecular mechanisms of targeted drugs. RESULTS:EGFR is expressed in 100% of ICCs, 52.6% of ECCs, and in 38.5% of GBCs. P-MAPK and p-Akt are highly expressed in ICCs (>58% of samples), and to a lower extent in ECCs and GBCs (<46%), indicating EGFR pathway activation. HER2 is overexpressed in 10% of GBCs (with genomic amplification), and 26.3% of ECCs (half of which has genomic amplification). EGFR or its signal transducers are mutated in 26.5% of cases: 4 samples bear mutations of PI3K (8.2%), 3 cases (6.1%) in K-RAS, 4 (8.2%) in B-RAF, and 2 cases (4.1%) in PTEN, but no loss of PTEN expression is detected. EGI-1 cell line is highly sensitive to gemcitabine, TFK1 and TGBC1-TKB cell lines are responsive and HuH28 cell line is resistant. In EGI-1 cells, combination with gefitinib further increases the antiproliferative effect of gemcitabine. In TFK1 and TGBC1-TKB cells, the efficacy of gemcitabine is increased with addiction of sorafenib and everolimus. In TGBC1-TKB cells, lapatinib also has a synergic effect with gemcitabine. HuH28 becomes responsive if treated in combination with erlotinib. Moreover, HuH28 cells are sensitive to lapatinib as a single agent. Molecular mechanisms were confirmed by western blot analysis. CONCLUSION:These data demonstrate that EGFR and HER2 pathways are suitable therapeutic targets for BTCs. The combination of gemcitabine with drugs targeting these pathways gives encouraging results and further clinical studies could be warranted.
journal_name
BMC Cancerjournal_title
BMC cancerauthors
Pignochino Y,Sarotto I,Peraldo-Neia C,Penachioni JY,Cavalloni G,Migliardi G,Casorzo L,Chiorino G,Risio M,Bardelli A,Aglietta M,Leone Fdoi
10.1186/1471-2407-10-631subject
Has Abstractpub_date
2010-11-18 00:00:00pages
631issn
1471-2407pii
1471-2407-10-631journal_volume
10pub_type
杂志文章相关文献
BMC CANCER文献大全abstract:BACKGROUND:Studies comparing the effect of antiangiogenic agents targeting different angiogenic pathways are sparse. The purpose of this study was to compare the effect of properdistatin and sunitinib treatment in a preclinical model of malignant melanoma. Properdistatin is a small peptide derived from the thrombospond...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-017-3404-4
更新日期:2017-06-12 00:00:00
abstract:BACKGROUND:No consensus treatment has been reached for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Hepatic resection (HR) and transarterial chemoembolization (TACE) have been recommended as effective options, but which is better remains unclear. This meta-analysis is to compare the effectiven...
journal_title:BMC cancer
pub_type: 杂志文章,meta分析,评审
doi:10.1186/s12885-017-3895-z
更新日期:2017-12-28 00:00:00
abstract:BACKGROUND:Migration is important for the metastatic capacity and thus for the malignancy of cancer cells. There is limited knowledge on regulatory factors that promote the migration of neuroblastoma cells. This study investigates the hypothesis that protein kinase C (PKC) isoforms regulate neuroblastoma cell motility....
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-8-365
更新日期:2008-12-11 00:00:00
abstract:BACKGROUND:The application of induction chemotherapy failed to provide a consistent benefit for local control in primary treatment of advanced head and neck (H&N) cancers. The aim of this study was to compare the results of concomitant application of radiochemotherapy for treating locally advanced head-and-neck carcino...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-6-30
更新日期:2006-02-01 00:00:00
abstract:BACKGROUND:The Src homology phosphotyrosyl phosphatase 2 (SHP2) is a positive effector of cell growth and survival signaling as well transformation induced by multiple tyrosine kinase oncogenes. Since the basal-like and triple-negative breast cancer (BTBC) is characterized by dysregulation of multiple tyrosine kinase o...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-015-1131-2
更新日期:2015-03-08 00:00:00
abstract:BACKGROUND:Deciphering the meaning of the human DNA is an outstanding goal which would revolutionize medicine and our way for treating diseases. In recent years, non-coding RNAs have attracted much attention and shown to be functional in part. Yet the importance of these RNAs especially for higher biological functions ...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-019-6338-1
更新日期:2019-12-03 00:00:00
abstract:BACKGROUND:In people with albinism (PWA), the deficiency of melanin increase the risk of skin cancers. The aim of this study was to determine the prevalence of skin cancers and characteristics of these detected skin cancers (histological types, localization) in PWA in 10 cities in Togo in 2019. METHODS:This is a cross...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-020-07747-8
更新日期:2021-01-05 00:00:00
abstract:BACKGROUND:BCA2 is an E3 ligase linked with hormone responsive breast cancers. We have demonstrated previously that the RING E3 ligase BCA2 has autoubiquitination activity and is a very unstable protein. Previously, only Rab7, tetherin, ubiquitin and UBC9 were known to directly interact with BCA2. METHODS:Here, additi...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-12-63
更新日期:2012-02-08 00:00:00
abstract:BACKGROUND:The causal association between persistent human papillomavirus (HPV) infection and cervical cancer has been established, but the mechanisms that favor HPV persistence in cervical cells are still unknown. The diminished capability of the immune system to control and resolve HPV infection is one of several hyp...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-12-618
更新日期:2012-12-24 00:00:00
abstract:BACKGROUND:Programmed cell death 1 (PD1) inhibitors have recently shown promising anti-cancer effects in a number of solid tumor types. A predictive biomarker to this class of drugs has not been clearly identified; however, overexpression of the PD1 ligand (PD-L1) has shown particular promise in lung adenocarcinoma. In...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-017-3634-5
更新日期:2017-09-05 00:00:00
abstract:BACKGROUND:Recent studies suggested that cancer stem-like cells contribute to tumor vasculogenesis by differentiating into endothelial cells. However, such process is governed by still undefined mechanism. METHODS:At varying differentiation levels, three representative colon cancer cells were cultured in endothelial-i...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-017-3578-9
更新日期:2017-08-30 00:00:00
abstract:BACKGROUND:Despite all benefit provided by established therapies prognosis of gastric cancer remains poor. Targeted inhibition of platelet derived growth factor receptor (PDGFR) by imatinib may influence tumor growth and amplify chemotherapeutic effects. METHODS:This phase I study evaluated dose limiting toxicity (DLT...
journal_title:BMC cancer
pub_type: 杂志文章,多中心研究
doi:10.1186/1471-2407-12-587
更新日期:2012-12-10 00:00:00
abstract:BACKGROUND:High-risk neuroblastoma with N-Myc amplification remains a therapeutic challenge in paediatric oncology. Antagonism of pro-death Bcl-2 homology (BH) proteins to pro-survival BH members such as Mcl-1 and Bcl-2 has become a treatment approach, but previous studies suggest that a combined inhibition of Bcl-2 an...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-019-5439-1
更新日期:2019-03-18 00:00:00
abstract:BACKGROUND:The objective of this systematic review and meta-analysis was to determine the prognostic value of total tumor-infiltrating lymphocytes (TILs) and subtypes of TILs (CD4+, CD8+, and FOXP3+) in triple-negative breast cancer (TNBC). METHODS:A systematic search of the MEDLINE, EMBASE, and Web of Science databas...
journal_title:BMC cancer
pub_type: 杂志文章,meta分析
doi:10.1186/s12885-020-6668-z
更新日期:2020-03-04 00:00:00
abstract:BACKGROUND:Mounting evidence shows that microRNA-34a (miR-34a) is involved in cancer prognosis. Therefore, we summarize the predictive role of miR-34a for survival in patients with gastrointestinal cancers (GICs). METHODS:All eligible studies were found by searching PubMed, Web of Science and EMBASE, and survival resu...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-020-07751-y
更新日期:2021-01-14 00:00:00
abstract:BACKGROUND:Multimodality treatment improves the chance of survival but increases the risk for long-term side effects in young cancer survivors, so-called" Adolescents and Young Adults"(AYAs). Compared to the general population AYAs have a 5 to 15-fold increased risk of cardiovascular morbidity. Thus, improving modifiab...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-016-2896-7
更新日期:2016-11-08 00:00:00
abstract:BACKGROUND:Head and neck squamous cell carcinoma (HNSCC) is the sixth most common tumor in human. Research has shown that HPV status HNSCC is a unique prognosis factor, which may due to its immune infiltration landscape. But the underlying mechanism is unclear. METHODS:In this study, we used a combination of several b...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-020-07298-y
更新日期:2020-08-24 00:00:00
abstract:BACKGROUND:There are three main therapeutic strategies, namely expectant management (dilation and curettage only), prophylactic chemotherapy and prophylactic total hysterectomy for treating older women with complete hydatidiform mole (CHM). However, the scientific community has so far, not unanimously accepted the abov...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-017-3749-8
更新日期:2017-11-09 00:00:00
abstract:BACKGROUND:Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature cells that accumulates in tumour-bearing hosts. These cells are induced by tumour-derived factors (e.g. prostaglandins) and have a critical role in immune suppression. MDSC suppress T and NK cell function via increased express...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-10-464
更新日期:2010-08-30 00:00:00
abstract:OBJECTIVES:The present study aims to evaluate long-term side-effects and outcomes and confirm prognostic factors after stereotactic body radiotherapy (SBRT) of pulmonary lesions. This is the first work that combines the investigated data from patient charts and patient-reported outcome (PRO) up to 14 years after therap...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-020-6635-8
更新日期:2020-05-19 00:00:00
abstract:BACKGROUND:To assess the safety and efficacy of simultaneous integrated boost (SIB) or late course accelerated boost (LCAB) with external beam radiotherapy (EBRT) to the vaginal cuff for high risk cervical cancer patients after radical hysterectomy. METHODS:Between October 2009 and January 2012, patients with high ris...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-015-1248-3
更新日期:2015-04-11 00:00:00
abstract:BACKGROUND:Aboriginal status has been unreliably and incompletely recorded in health and vital registration data collections for the most populous areas of Australia, including NSW where 29% of Australian Aboriginal people reside. This paper reports an assessment of Aboriginal status recording in NSW cancer registratio...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-12-168
更新日期:2012-05-06 00:00:00
abstract:BACKGROUND:Renal cell carcinoma (RCC) is a malignant disease that demonstrates resistance to standard chemotherapeutic agents. Yet Active immunization using genetically modified dendritic cells holds promise for the adjuvant treatment of malignancies to eradicate or control residual disease. Cytokine-induced killer (CI...
journal_title:BMC cancer
pub_type: 临床试验,杂志文章
doi:10.1186/1471-2407-14-251
更新日期:2014-04-10 00:00:00
abstract:BACKGROUND:As inadequate pain communication contributes to difficulties in optimizing outcomes of outpatients, we investigated the effect of reinforced education using WeChat App to the opioid titration treatment of cancer-related pain in the outpatient setting. METHODS:We conducted a prospective study to compare rein...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-020-07270-w
更新日期:2020-09-04 00:00:00
abstract:BACKGROUND:Crosstalk between malignant hepatocytes and the surrounding peritumoral stroma is a key modulator of hepatocarcinogenesis and therapeutic resistance. To examine the chemotherapy resistance of these two cellular compartments in vitro, we evaluated a well-established hepatic tumor cell line, HepG2, and an adul...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-12-402
更新日期:2012-09-10 00:00:00
abstract:BACKGROUND:To date, the clinical benefit of topical steroid use has only been demonstrated for radiation dermatitis induced by 50-60 Gy irradiation in breast cancer. However, these agents are also often used clinically for the control of radiation dermatitis induced by high-dose (>60Gy) irradiation with chemotherapy in...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-018-4763-1
更新日期:2018-09-06 00:00:00
abstract:BACKGROUND:Stereotactic radiotherapy is an emerging treatment option for patients with inoperable renal cell carcinoma (RCC). Haemorrhage has not previously been reported to occur as a result of Stereotactic Body Radiotherapy (SBRT) to the kidney for primary RCC. We report an acute haemorrhage in a patient who received...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/s12885-019-5899-3
更新日期:2019-07-08 00:00:00
abstract:BACKGROUND:The preoperative characterization of thyroid nodules is a challenge for the clinicians. Fine-needle aspiration (FNA) is the commonly used pre-operative technique for diagnosis of malignant thyroid tumor. However, many benign lesions, with indeterminate diagnosis following FNA, are referred to surgery. There ...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-14-492
更新日期:2014-07-08 00:00:00
abstract:BACKGROUND:Although cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome. Also cisplatin accumulation shows toxicity to normal tissues. In this study, we examined the possibility of HemoHIM both to enhance anticancer effect with cisplatin an...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-9-85
更新日期:2009-03-17 00:00:00
abstract:BACKGROUND:MicroRNAs are the endogenous small non-coding RNA molecules capable of silencing protein coding genes at the posttranscriptional level. Based on computer-aided predictions, a single microRNA could have over a hundred of targets. On the other hand, a single protein-coding gene could be targeted by many potent...
journal_title:BMC cancer
pub_type: 杂志文章
doi:10.1186/1471-2407-9-194
更新日期:2009-06-18 00:00:00