Abstract:
BACKGROUND:Pancreatic cancer is one of the most aggressive and intractable malignant tumors, and most deaths from pancreatic cancer are related to metastases. It has been demonstrated in vitro that overexpression of programmed death-ligand 1 (PD-L1) correlates with a lack of phosphatase and tensin homologue (PTEN) expression in pancreatic cancer tissue. This loss of PTEN expression may aberrantly activate the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway, and thereby promote tumor cell survival, proliferation, and disease progression. In this study, we investigated the potential therapeutic effect of blockading PD-L1 expression on the progression of pancreatic cancer and its spontaneous liver metastases in vivo by inhibiting the PI3K/Akt/mTOR signaling pathway. METHODS:We investigated the effect of blockading PD-L1 in an orthotopic pancreatic cancer mouse model. The pancreatic tumor weights and inhibition ratios were determined after treatment with antimouse PD-L1 antibody for 5 weeks. We used immunohistochemistry methods to investigate PD-L1 expression in pancreatic cancer tissue and spontaneous liver metastasis tissue. The levels of mRNA and protein expression for various components involved in the PI3K/Akt/mTOR signaling pathway as well as for matrix metalloproteinases-2 and -9 (MMP2 and MMP9) were measured by reverse transcription polymerase chain reaction (RT-PCR) and Western blot methods, respectively. RESULTS:Blockading PD-L1 significantly inhibited tumor growth and decreased the levels of PD-L1 expression in tumor tissue. Furthermore, the levels of PTEN mRNA and protein expression were elevated, while the levels of phospho-Akt (p-Akt) and phospho-mTOR (p-mTOR) protein were decreased in pancreatic cancer and liver metastasis tissues after establishing a PD-L1 blockade. In addition, a PD-L1 blockade decreased the levels of MMP2 and MMP9 mRNA and protein expression in tumor tissues. CONCLUSION:Our results suggest that a blockade of PD-L1 may inhibit the growth and metastasis of pancreatic cancer by modulating the PI3K/Akt/mTOR pathway.
journal_name
Onco Targets Therjournal_title
OncoTargets and therapyauthors
Zhao L,Li C,Liu F,Zhao Y,Liu J,Hua Y,Liu J,Huang J,Ge Cdoi
10.2147/OTT.S130481subject
Has Abstractpub_date
2017-04-12 00:00:00pages
2115-2126issn
1178-6930pii
ott-10-2115journal_volume
10pub_type
杂志文章abstract:PURPOSE:Although numerous studies have demonstrated associations between the preoperative neutrophil-to-lymphocyte ratio (NLR) and long-term outcomes in patients with non-small cell lung cancer (NSCLC), the prognostic significance of postoperative NLR and change in NLR (ΔNLR) is unknown for patients who underwent compl...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S117290
更新日期:2016-10-21 00:00:00
abstract::Neuroendocrine tumors are a rare and heterogeneous group of tumors with a variety of primary origins and variable aggressiveness. Platinum-based chemotherapy has been the cornerstone of treatment for the poorly differentiated tumors. However, well-differentiated neuroendocrine tumors are quite chemoresistant and thera...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S72155
更新日期:2016-02-09 00:00:00
abstract::Patients with Lynch Syndrome (LS) are at high risk of developing colorectal cancer at an early age. Germline mutations in DNA mismatch repair genes and microsatellite instability are clear signatures of this autosomal dominant disorder. Here, we report the clinical history of a 38-year-old patient with LS-related meta...
journal_title:OncoTargets and therapy
pub_type:
doi:10.2147/OTT.S167645
更新日期:2018-10-23 00:00:00
abstract:Purpose:The molecular mechanism of perineural invasion (PNI) in stage II colorectal cancer (CRC) remains not to be defined clearly. This study aims to identify the genomic aberrations related to PNI in stage II CRC. Patients and Methods:Using array-based comparative genomic hybridization (array-CGH), primary tumor tis...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S264616
更新日期:2020-11-11 00:00:00
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:BACKGROUND:Permanent prostate brachytherapy (PPB) is an effective treatment choice for low and intermediate risk prostate cancer (PCa). However, the impact of PPB on tumor immune status is still poorly understood. This study aimed to assess the immune status in PCa patients before and at different time points after PPB...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S137491
更新日期:2017-05-15 00:00:00
abstract:OBJECTIVE:The objective of the present investigation was to study the clinical significances of the abnormal expressions of Piwil1 and Piwil2 protein in colonic adenoma and adenocarcinoma. METHODS:This study had applied immunohistochemical method to detect 45 cases of tissues adjacent to carcinoma (distance to cancero...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S77003
更新日期:2015-05-27 00:00:00
abstract::Multiple drug resistance is still an unsolved problem in cancer therapy. Our previous study demonstrated that the chemotherapeutic drug doxorubicin (Dox) induced upregulation of P-glycoprotein (P-gp) in endothelial cells, resulting in a 20-fold increase in drug resistance and reduced efficiency of Dox treatment in a m...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S67251
更新日期:2014-12-04 00:00:00
abstract::[This retracts the article on p. 2215 in vol. 8, PMID: 26345468.]. ...
journal_title:OncoTargets and therapy
pub_type: 撤回出版物
doi:10.2147/OTT.S100941
更新日期:2016-02-04 00:00:00
abstract:BACKGROUND:CD155, an immunoglobulin-like adhesion molecule, plays an important role in carcinoma such as cells migration, proliferation, metastasis, and tumor immune. The upregulation of CD155 has been found in several human malignancies, but its expression in cholangiocarcinoma (CCA) still remains unclear. The aim of ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S141476
更新日期:2017-07-31 00:00:00
abstract:OBJECTIVE:Resveratrol is a phytoestrogen with various antiproliferative and proapoptotic effects. This in vitro study aimed to analyze the effect of resveratrol on the viability and expression of modulators of apoptosis in GH3 pituitary adenoma cells of the rat. METHODS:GH3 cells were incubated with resveratrol concen...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S45154
更新日期:2013-09-16 00:00:00
abstract:Introduction:Hypoxia and tumor-associated macrophage (TAM) are key regulators in remodeling the microenvironment of esophageal squamous cell carcinoma (ESCC). Hypoxia could stimulate tumor cells to secrete more exosomes and activate TAMs to M2 type. Here, we investigated the function and the underlying mechanism of tum...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S284192
更新日期:2020-11-18 00:00:00
abstract:AIMS:Metastasis-associated gene 2 (MTA2) is reported to play an important role in tumor progression, but little is known about the role of MTA2 in nasopharyngeal carcinoma (NPC). The aim of the study was to explore the expression and function of MTA2 in NPC. METHODS:Expression of MTA2 in NPC tissues and cell lines was...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S96518
更新日期:2016-03-18 00:00:00
abstract::ALK rearrangements account for ~5% of non-small-cell lung cancer (NSCLC). Numerous rearrangement partners have been discovered. Here, we describe a 53-year-old nonsmoker with NSCLC, in whom we identified four novel rearrangements. The patient was diagnosed as adenocarcinoma in the right middle lobe of lung, with metas...
journal_title:OncoTargets and therapy
pub_type:
doi:10.2147/OTT.S258067
更新日期:2020-08-20 00:00:00
abstract::EGFR pathway is an important therapeutic target in human tumors, including metastatic colorectal cancer (mCRC). The advent of EGFR-targeted monoclonal antibodies panitumumab and cetuximab has generated promise for the treatment of mCRC and has largely improved patients' progression-free survival (PFS) and overall surv...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S86966
更新日期:2016-01-27 00:00:00
abstract::We report the case of a man with an advanced nonkeratinizing squamous cell thymic carcinoma harboring c-KIT exon 13 missense mutation K642E. This aberration is rare and has never been described previously in patients with thymic cancers. It has been found in a small number of cases of gastrointestinal stromal tumor an...
journal_title:OncoTargets and therapy
pub_type:
doi:10.2147/OTT.S58902
更新日期:2014-05-08 00:00:00
abstract::Malignant pericardial effusion (MPCE) is a common complication of advanced malignant tumors, and interferes severely with patient prognosis and quality of life. The standard treatment for this complication is intracavitary perfusion of chemotherapeutic drugs, which is limited by unsatisfactory therapeutic effects and ...
journal_title:OncoTargets and therapy
pub_type:
doi:10.2147/OTT.S90145
更新日期:2015-10-01 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::Human testis development-related gene 1 (TDRG1) is a recently identified gene that is expressed exclusively in the testes and promotes the development of testicular germ cell tumors. In this study, the role of TDRG1 in the development of testicular seminoma, which is the most common testicular germ cell tumor, was fur...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S97294
更新日期:2016-01-20 00:00:00
abstract::Introduction: In recent years, an increasing amount of literature has demonstrated the functional role of long non-coding RNA (lncRNA) in human diseases. LINC00515 is a newly defined lncRNA and is reported to act as an oncogene in multiple myeloma. However, the function of LINC00515 in glioma is still uncertain. Mater...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S198087
更新日期:2019-04-08 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:Background:Galangin (GLN), a pure natural flavonoid compound found in plants, has been shown to exert anti-cancer effects against multiple cancer types, including glioma. However, its underlying molecular mechanism remains unclear. Epithelial-to-mesenchymal transition (EMT) performs an important function in the genesis...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S264209
更新日期:2020-09-17 00:00:00
abstract:Background:It was previously reported that downregulation of miR-218 promoted thyroid cancer cell invasion, migration, and proliferation. However, the biological functions of miR-218 and its possible regulatory mechanisms in papillary thyroid cancer (PTC) cells are still elusive. Materials and methods:The expression l...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S172152
更新日期:2018-09-28 00:00:00
abstract:AIM:To investigate the clinical significance of cyclic adenosine monophosphate-responsive element-binding (CREB) and phosphorylated CREB (pCREB) expression in human hepatocellular carcinoma (HCC). MATERIALS AND METHODS:Immunohistochemistry and Western blot analyses were performed to detect the expression and subcellul...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S63594
更新日期:2014-05-29 00:00:00
abstract:Background:Breast cancer (BC) has been the commonest malignant tumor with a low survival rate among woman. Long non-coding RNA hypoxia-inducible factor-1 alpha antisense RNA-2 (HIF1A-AS2) was correlated with various cancers. Purpose:The study aimed to investigate the roles and related underlying molecular mechanisms o...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S192377
更新日期:2019-01-24 00:00:00
abstract:Purpose:Primary squamous cell carcinoma is a rare malignancy in the thyroid gland (SCCTh). The overall prognosis of this carcinoma is poor. This study aimed to explore the application of Raman spectroscopy in investigating the expression of CK5/6 and P63 in SCCTh. Patients and Methods:Tissues of the SCCTh and adjacent...
journal_title:OncoTargets and therapy
pub_type:
doi:10.2147/OTT.S229436
更新日期:2020-01-20 00:00:00
abstract:Purpose:B7 homologue 6 (B7-H6) has been found at an up-regulated level in multiple cancer cells and identified to be positively correlated with inferior clinical features. In non-Hodgkin lymphoma (NHL), however, the roles of B7-H6 and the underlying mechanism of action remain unclear. Through in vivo and in vitro exper...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S257512
更新日期:2020-06-18 00:00:00
abstract:BACKGROUND:The PI3K family participates in multiple signaling pathways to regulate cellular functions. PI3K/Akt signaling pathway plays an important role in tumorigenesis and development. O-GlcNAcylation, a posttranslational modification, is thought to modulate a wide range of biological processes, such as transcriptio...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S82845
更新日期:2015-11-09 00:00:00
abstract::Esophageal carcinoma (EC) is a lethal disease with high morbidity and mortality worldwide, and the incidence has been increasing in recent years. Although the diagnosis and treatment of EC have improved considerably, EC has rapidly progressed in the clinical setting and has a poor prognosis for its metastasis and recu...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S103179
更新日期:2016-04-19 00:00:00
abstract:Purpose:Minimally invasive esophagectomy is increasingly performed for esophageal or gastroesophageal junctional cancer, with advantages of improved perioperative outcomes in comparison with open esophagectomy. McKeown and Ivor Lewis are widely used procedures of minimally invasive esophagectomy, and there have been co...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S169488
更新日期:2018-09-20 00:00:00