Abstract：
:Targeting phosphatidylinositol 3-kinase δ (PI3Kδ) is an important therapeutic strategy for indolent non-Hodgkin lymphomas (NHLs). However, we previously observed reactivation of phosphatidylinositol 3-kinase (PI3K) pathways in aggressive NHL cell lines following continuous exposure to PI3Kδ inhibitors (PI3Kδi), which limited their efficacy and suggests that more studies should be focused on this reactivation to improve current PI3Kδi-based treatments. Herein we conducted a drug synergy screening that combined a marketed PI3Kδi, idelalisib, with 14 well-characterized epigenetic drugs across several types of aggressive NHL cell lines. We identified BRD4 inhibitors (BRD4i) as potent partners that, in combination with idelalisib, were capable of synergistically exerting anti-proliferative activity and inducing cell apoptosis in a panel of aggressive NHL cell lines through continuous suppression of PI3K pathways. More importantly, the combination of BRD4i and PI3Kδi simultaneously inhibited transcription and translation of the oncogenic transcription factor c-MYC, downregulating the expression of c-MYC and continuously suppressing the proliferation of cancer cells in vitro, as well as the growth of tumors in vivo even after drug withdrawal. This study, thus, reveals the potential of simultaneously targeting PI3Kδ and BRD4 as a new therapeutic strategy for aggressive forms of NHL.
journal_name
Am J Cancer Resjournal_title
American journal of cancer researchauthors
Zuo W,Zhu Y,Liu Z,Xia Y,Xu Y,Peng C,Yu L,Wang Nsubject
Has Abstractpub_date
2021-01-01 00:00:00pages
215-235issue
1issn
2156-6976journal_volume
11pub_type
杂志文章abstract：:Increasing evidence reveals that deregulation of miRNAs contributes to carcinogenesis of the human non-small cell lung cancer (NSCLC). Our study discovered that the expression of miR-449a was markedly decreased in NSCLC cells with high metastatic capacity and tissues of positive lymph node metastasis. Moreover, our re...
journal_title：American journal of cancer research
pub_type： 杂志文章
doi：
更新日期：2015-08-15 00:00:00
abstract：:Evidence suggests that over-expression of TWIST, an epithelial-mesenchymal transition inducer, might have a correlation with cancer progression and chemoresistance. However, its roles in radioresistance of cancer have rarely been reported. High TWIST expression was detected in nasopharyngeal carcinoma (NPC) and associ...
journal_title：American journal of cancer research
pub_type： 杂志文章
doi：
更新日期：2015-03-15 00:00:00
abstract：:Human transcriptional positive cofactor 4 (PC4) is a novel marker for diagnosis and treatment of advanced human cancers metastasis. In human lung adenocarcinoma, tumor lymphangiogenesis, an important early event, can promotes lymphatic metastasis, while it has been reported that VEGF-C/VEGF-D/VEGFR-3 axis plays an imp...
journal_title：American journal of cancer research
pub_type： 杂志文章
doi：
更新日期：2015-05-15 00:00:00
abstract：:In addition to direct oncolysis, oncolytic viruses trigger immunogenic cell death (ICD) and primes antitumor immunity. We have previously shown that oncolytic Newcastle disease virus (NDV), strain FMW (NDV/FMW), induces apoptosis and/or autophagy in cancer cells. In this study, we investigated whether oncolytic NDV ca...
journal_title：American journal of cancer research
pub_type： 杂志文章
doi：
更新日期：2018-08-01 00:00:00
abstract：:CBX7 is a polycomb protein that participates in the formation of polycomb repressive complex 1. Apart from few exceptions, CBX7 expression is lost in human malignant neoplasias and a clear correlation between its downregulated expression and a cancer aggressiveness and poor prognosis has been observed. These findings ...
journal_title：American journal of cancer research
pub_type： 杂志文章,评审
doi：
更新日期：2015-04-15 00:00:00
abstract：:Pancreatic cancer (PC) is one of the most malignant tumors. Rho GTPases can affect several types of human cancers, including PC. In this study, we investigated the role of Ras homolog family member T1 (RHOT1), a new member of Rho GTPases in PC. IHC results showed that RHOT1 was expressed significantly higher in PC tis...
journal_title：American journal of cancer research
pub_type： 杂志文章
doi：
更新日期：2015-03-15 00:00:00
abstract：:Epidermal growth factor receptor (EGFR) is highly expressed in head and neck squamous cell carcinoma (HNSCC) and related to cancer progression. The resistance to anti-EGFR therapy remains a major clinical problem in HNSCC. In this study, we found that TOLL-like receptor 4 (TLR4) was highly expressed in 50% of EGFR ove...
journal_title：American journal of cancer research
pub_type： 杂志文章
doi：
更新日期：2020-02-01 00:00:00
abstract：:Napabucasin (NAPA) is thought to be a potent cancer stemness inhibitor in different types of cancer cell lines. While it has shown promising activity in early phase clinical trials, two recent phase III NAPA clinical trials failed to meet the primary endpoint of overall survival. The reason for the failure is not clea...
journal_title：American journal of cancer research
pub_type： 杂志文章
doi：
更新日期：2020-05-01 00:00:00
abstract：:RNA binding motif, single stranded interacting protein 3 (RBMS3) has been reported as a tumor suppressor gene (TSG) in some squamous carcinoma. However, its expression levels and clinical significance in gastric cancer (GC) remains unclear. Secreted frizzled-related protein 1 (SFRP1) plays a role of tumor suppressor i...
journal_title：American journal of cancer research
pub_type： 杂志文章
doi：
更新日期：2016-11-01 00:00:00
abstract：:2-amino-1-methyl-6-phenylimidazo[4,5b]pyridine (PhIP) is a dietary mutagenic carcinogen that has been shown not only to induce the formation of DNA adducts, but is capable of inducing tumors in the colon, mammary, and prostate glands. The normal development and maturation of the prostate gland, as well as early progre...
journal_title：American journal of cancer research
pub_type： 杂志文章
doi：
更新日期：2014-12-15 00:00:00
abstract：:Circular RNAs (circRNAs) are a series of special closed circular RNA molecules with stability and conservatism. In recent years, advances in high-throughput RNA sequencing technology have led to explosive discovery of circRNAs in different types of species and cells. Moreover, circRNAs can accomplish a remarkable mult...
journal_title：American journal of cancer research
pub_type： 杂志文章,评审
doi：
更新日期：2018-07-01 00:00:00
abstract：:Trifluridine/tipiracil (FTD/TPI or TFTD, also known as TAS-102) with a molar ratio of 1:0.5, is a novel combination of FTD, an antineoplastic thymidine analog, and TPI, an inhibitor of thymidine phosphorylase. It has been approved as a treatment for unresectable advanced or recurrent colorectal cancer. Irinotecan (CPT...
journal_title：American journal of cancer research
pub_type： 杂志文章
doi：
更新日期：2017-12-01 00:00:00
abstract：:The low solubility of cisplatin in aqueous solution limits the treatment effectiveness and the application of cisplatin in various kinds of drug-eluting devices. Although cisplatin has a high solubility in Dimethyl sulfoxide (DMSO), the toxicity of cisplatin can be greatly reduced while dissolved in DMSO. In this stud...
journal_title：American journal of cancer research
pub_type： 杂志文章
doi：
更新日期：2015-01-15 00:00:00
abstract：:Epithelial ovarian cancer is a malignancy with high rate of death due to an advanced disease at diagnosis and frequent relapse after chemotherapy. Nowadays, there is a lack of knowledge for clear risk factors and predictive and/or prognostic genetic markers although genomic alterations such as mutations in p53, PTEN, ...
journal_title：American journal of cancer research
pub_type： 杂志文章
doi：
更新日期：2012-01-01 00:00:00
abstract：:Circular RNAs (circRNAs) have been shown to regulate the development and progression of various cancers. However, the expression and function of circRNAs in papillary thyroid cancer (PTC) remain largely unknown. This study is aimed to investigate the potential roles of circEIF3I in PTC and elucidate the functional mec...
journal_title：American journal of cancer research
pub_type： 杂志文章
doi：
更新日期：2020-04-01 00:00:00
abstract：:OSCP1/NOR1 (organic solute carrier partner 1/oxidored-nitro domain-containing protein 1) is known as a transporter of various organic solutes into cells and also is reported to act as a tumor suppressor protein. Although overexpression of OSCP1 has been shown to play multiple roles in mammalian cell lines, its biologi...
journal_title：American journal of cancer research
pub_type： 杂志文章
doi：
更新日期：2015-04-15 00:00:00
abstract：:Due to the refractory and partial sensitive treatments to malignant cancers, immunotherapy has increasingly become a hotspot in effective anti-tumor research. However, at present, existing animal models could not accurately describe the interaction between human tissue and tumor cells for preclinical trials. Furthermo...
journal_title：American journal of cancer research
pub_type： 杂志文章,评审
doi：
更新日期：2020-12-01 00:00:00
abstract：:[This corrects the article on p. 1252 in vol. 7, PMID: 28670489.]. ...
journal_title：American journal of cancer research
pub_type： 杂志文章,已发布勘误
doi：
更新日期：2020-06-01 00:00:00
abstract：:Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor A (VEGF-A), was used in combination with traditional chemotherapy as the first line treatment for metastatic colorectal cancer (mCRC), non-small cell lung cancer (NSCLC) and advanced ovarian cancer. However, it shows limited efficacy for h...
journal_title：American journal of cancer research
pub_type： 杂志文章
doi：
更新日期：2019-08-01 00:00:00
abstract：:microRNAs (miRNAs) are frequently aberrantly expressed in osteosarcoma (OS) and are implicated in its development. Dysregulation of miR-758 has been reported in various human malignancies. However, whether miR-758 is involved in the oncogenesis and progression of OS remains unclear. In this study, reverse transcriptio...
journal_title：American journal of cancer research
pub_type： 杂志文章
doi：
更新日期：2019-01-01 00:00:00
abstract：:Radiation remains an important component of cancer treatment. In addition to inducing tumor cell death through direct cytotoxic effects, radiation can also promote the regression of tumor via augment of immune response. Regulatory T cells (Tregs) are a unique subpopulation of CD4 positive cells, which are characterize...
journal_title：American journal of cancer research
pub_type： 杂志文章,评审
doi：
更新日期：2015-10-15 00:00:00
abstract：:The trans-activation response DNA-binding protein of 43 kDa (TDP-43) is a nuclear protein that has been shown to be involved in the growth and metastasis of breast cancer, neuroblastoma, and melanoma. However, the effect of TDP-43 on hepatocellular carcinoma (HCC) metastasis remains unclear. Here, we demonstrated that...
journal_title：American journal of cancer research
pub_type： 杂志文章
doi：
更新日期：2020-10-01 00:00:00
abstract：:Omega-3 polyunsaturated fatty acids (PUFAs), such as those found in fish oil, are thought to have anti-tumorigenic effects and may help to treat and prevent cancer, including ovarian cancer. Thus, we aimed to evaluate the potential of docosahexaenoic acid (DHA), an omega-3 PUFA, as a therapeutic agent in ovarian cance...
journal_title：American journal of cancer research
pub_type： 杂志文章
doi：
更新日期：2020-12-01 00:00:00
abstract：:Rottlerin, a natural product isolated from Mallotus philippinensis, has been characterized as an effective chemoprevention agent in inhibiting tumor cell growth. Although multiple studies have revealed the role of rottlerin in tumorigenesis, the molecular mechanism of rottlerin-mediated anti-tumor activity has not bee...
journal_title：American journal of cancer research
pub_type： 杂志文章
doi：
更新日期：2016-10-01 00:00:00
abstract：:Sexual dimorphism in the incidence of human esophageal cancer, including both esophageal adenocarcinoma and squamous cell carcinoma, shows male dominancy. However, the mechanisms that underlie sexual dimorphism of esophageal cancer have been understudied in vivo due to the lack of sex-dimorphic mouse models. Here, we ...
journal_title：American journal of cancer research
pub_type： 杂志文章
doi：
更新日期：2019-02-01 00:00:00
abstract：:Podoplanin is a small membrane glycoprotein with a large number of O-glycoside chains and therefore it belongs to mucin-type proteins. It can be found on the surface of many types of normal cells originating from various germ layers. It is present primarily on the endothelium of lymphatic vessels, type I pneumocytes a...
journal_title：American journal of cancer research
pub_type： 杂志文章,评审
doi：
更新日期：2016-01-15 00:00:00
abstract：:Glioma is one of the most common, rapidly progressive and fatal brain tumors, and accumulating evidence shows that microRNAs (miRNAs) play important roles in the development of cancers, including glioma. Therapeutic applications of miRNAs in Ras-driven glioma have been proposed; however, their specific functions and m...
journal_title：American journal of cancer research
pub_type： 杂志文章
doi：
更新日期：2017-04-01 00:00:00
abstract：BACKGROUND:Chemotherapy resistance is a common problem faced by patients diagnosed with epithelial ovarian cancer (EOC). Currently there are no specific or sensitive clinical biomarkers that maybe implemented to identify chemotherapy resistance and give insight to prognosis. The aim of this study is to investigate the ...
journal_title：American journal of cancer research
pub_type： 杂志文章
doi：
更新日期：2015-01-15 00:00:00
abstract：:[This retracts the article on p. 2865 in vol. 5, PMID: 26609492.]. ...
journal_title：American journal of cancer research
pub_type： 撤回出版物
doi：
更新日期：2015-12-15 00:00:00
abstract：:Pyruvate kinase is a key enzyme in the glycolytic pathway that converts phosphoenolpyruvate to pyruvate, and the M2 isoform of pyruvate kinase (PKM2) is associated with cancer. PKM2 has been reported to function independently of its pyruvate kinase activity, which is crucial for cancer cell proliferation. Moreover, th...
journal_title：American journal of cancer research
pub_type： 杂志文章
doi：
更新日期：2016-02-15 00:00:00
