Abstract:
:Hepatocellular carcinoma (HCC) is the sixth most common cancer, and the third most common cause of cancer related death worldwide. The multi-kinase inhibitor Sorafenib represents the only systemic treatment option until today, and results from clinical trials with allosteric mTOR inhibitors were sobering. Since the PI3K/AKT/mTOR and RAF/MEK/ERK signaling pathways are frequently upregulated in HCC, we have analyzed the effects of AKT inhibitor MK-2206, MEK inhibitor AZD6244 (ARRY 142886) and mTOR kinase inhibitor AZD8055, given as single drugs or in combination, on proliferation and apoptosis of three HCC cell lines in vitro. We show that all three inhibitor combinations synergistically inhibit proliferation of the three HCC cell lines, with the strongest synergistic effect observed after vertical inhibition of AKT and mTORC1/2. We demonstrate that AKT kinase activity is restored 24h after blockade of mTORC1/2 by increased phosphorylation of T308, providing a rationale for combined targeting of AKT and mTOR inhibition in HCC. Our data suggest that a combination of inhibitors targeting those respective pathways may be a viable approach for future application in patients with hepatocellular carcinoma.
journal_name
J Cancerjournal_title
Journal of Cancerauthors
Ewald F,Nörz D,Grottke A,Bach J,Herzberger C,Hofmann BT,Nashan B,Jücker Mdoi
10.7150/jca.12452subject
Has Abstractpub_date
2015-09-16 00:00:00pages
1195-205issue
12issn
1837-9664pii
jcav06p1195journal_volume
6pub_type
杂志文章abstract::Mechanistic target of rapamycin (mTOR) plays a critical role in the development of oral squamous cell carcinoma (OSCC), but the underlying mechanisms remain poorly understood. Here we have demonstrated that the expression of osteopontin (OPN) was dramatically up-regulated in OSCC tissues and cell lines. Moreover, redu...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.18031
更新日期:2017-05-12 00:00:00
abstract::Objectives: Lung cancer in young adults is a distinct disease with particular socioeconomic implications. This study aimed to clarify the clinicopathological characteristics, best interventions, and outcomes of this distinctive entity. Methods: A retrospective review of patients with lung cancer was performed in our i...
journal_title:Journal of Cancer
pub_type: 杂志文章,评审
doi:10.7150/jca.27490
更新日期:2019-06-09 00:00:00
abstract::Preoperative chemoradiation followed by surgery has been recommended as a standard treatment for patients with stage II/III rectal cancer. However, the optimal sequencing of radiotherapy for metastatic rectal cancer remains unclear. Between 2004 and 2014, patients diagnosed with metastatic rectal cancer who underwent ...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.28320
更新日期:2019-01-30 00:00:00
abstract:BACKGROUND:MicroRNA (miRNA) have been shown to regulate gene expression in many cancers. MiR-182 has recently been found to be prognostic for patients treated with radical prostatectomy for prostate cancer. We sought to assess miR-182 as a prognostic marker and understand its role in prostate cancer progression and met...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.13176
更新日期:2015-10-25 00:00:00
abstract::Purpose: We explored the influence of age on clinicopathologic features and survival of patients with M0 gastric cancer (GC). Methods: 16856 GC patients from Surveillance, Epidemiology and End Results (SEER) database and 1037 GC patients from Chinese multiple centers were enrolled in the U.S. and Chinese cohort, respe...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.22085
更新日期:2018-03-08 00:00:00
abstract::Cancer cells express epithelial markers, and when progressing in malignancy they may express markers of the mesenchymal cell type. Therefore an epithelial-mesenchymal transition of the cancer cells is assumed. However the mesenchymal markers can equally well be interpreted as myeloid markers since they are common in b...
journal_title:Journal of Cancer
pub_type: 杂志文章,评审
doi:10.7150/jca.8242
更新日期:2014-01-15 00:00:00
abstract::Objectives: PD-1 and PD-L1 overexpression in malignant tumors in response to radiotherapy is correlated with a poor prognosis. Human papilloma virus (HPV) infection impacts intrinsic radiosensitivity of head and neck cancers (HNCs). Herein, this study aims to determine PD-1/PD-L1 expression differences in tumors with ...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.27199
更新日期:2019-01-29 00:00:00
abstract::Background: Anti-EGFR therapies have been recommended for advanced colorectal cancer (CRC) with wild-type RAS and PIK3CA mutation. However, PIK3CA mutations are a poor prognostic marker and a negative predictor of response to anti-EGFR therapies in RAS wild-type CRC. Therefore, new and advanced treatment strategies ar...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.19458
更新日期:2017-08-22 00:00:00
abstract::Tyrosine phosphorylation is an important post-translation modification of proteins that is controlled by tyrosine kinases and phosphatases. Disruption of the balance between the activity of tyrosine kinases and phosphatases may result in diseases. Receptor type protein tyrosine phosphatase epsilon (PTPRE) is closely r...
journal_title:Journal of Cancer
pub_type: 杂志文章,评审
doi:10.7150/jca.27633
更新日期:2019-01-01 00:00:00
abstract::Background: Hepatitis B virus infection had been identified its relationship with liver diseases, including liver tumors. We aimed to explore diagnostic and prognostic values between the Human Leukocyte Antigen (HLA) complex and hepatocellular carcinoma (HCC). Methods: We used the GSE14520 dataset to explore diagnosti...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.29655
更新日期:2019-08-28 00:00:00
abstract::Aim: Skin cutaneous melanoma (SKCM) is one of the most life-threatening malignancies damaging human health. APOBEC3G (A3G) has been found in several cancers; however, the role of A3G in SKCM is rarely studied. This study aimed to investigate the expression of A3G in tumor tissue and its prognostic value in SKCM patien...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.46383
更新日期:2020-07-06 00:00:00
abstract::Objective: This study aimed to evaluate the therapeutic response of hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE) with diffusion kurtosis imaging (DKI). Methods: Forty-three patients with fifty-nine hepatic cancer nodules were recruited for this study. All patients were treated b...
journal_title:Journal of Cancer
pub_type: 杂志文章,评审
doi:10.7150/jca.32491
更新日期:2020-02-10 00:00:00
abstract::Apurinic/apyrimidinic endonuclease 1 (APE1) is an essential enzyme in the base excision repair pathway. Epidemiological studies have suggested associations between APE1 rs1760944 polymorphism and cancer risk. This study was aimed to evaluate the relationship between APE1 rs1760944 polymorphism and cancer risk. We sear...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.8085
更新日期:2014-03-13 00:00:00
abstract::Background: To elucidate the expression of Aurora kinases (AURK) and the anticancer effects of pan-aurora kinase inhibitor Danusertib in hepatocarcinogenesis model in C56Bl6 mice. Methods: Thirty mice C56Bl6 were randomly divided into Group A or control, Group B animals who underwent experimental hepatocarcinogenesis ...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.22329
更新日期:2018-02-27 00:00:00
abstract:OBJECTIVE(S):To assess skeletal wide fracture location and time of fracture after cancer treatment Study Design: One hundred thirty-nine women diagnosed with breast or gynecologic cancer between 2003 and 2012 that subsequently had a radiologic diagnosis of fracture were identified retrospectively using electronic medic...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.10288
更新日期:2015-01-01 00:00:00
abstract::Background: Uterine cervical cancer (UCC) is a common malignant tumor in women. We conducted this work to provide a though description on the patterns of distant metastases and to investigate the relevant factors for prognosis of UCC patients based on a large population. Patients and methods: UCC patients with FIGO st...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.37390
更新日期:2020-01-14 00:00:00
abstract::Background: Sorafenib has been recommended as the standard therapy for advanced HCC with extrahepatic metastasis. The purpose of this retrospective study was to investigate the difference in overall survival (OS) between treatments with sorafenib combined with regional therapies versus sorafenib monotherapy in hepatoc...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.24568
更新日期:2018-04-19 00:00:00
abstract:OBJECTIVE:The main aim of this study was to study swith of the ovarian cancer cell to a calcifying phenotype in the formation of calcification in ovarian cancer, and to offer some help for ovarian cancer's diagnosis and differentiation therapy. METHODS:The mineralization of ovarian cancer cell lines SKOV3 was induced ...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.22932
更新日期:2018-02-28 00:00:00
abstract::Long non-coding RNAs (lncRNAs) have been considered as biomarkers for the carcinogenesis and development of various cancers. However, the prognostic significance of lncRNAs in renal cell carcinoma (RCC) remains unclear. This study aimed to determine the predictive ability of lncRNAs in clear cell RCC (ccRCC). Among th...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.40421
更新日期:2020-04-27 00:00:00
abstract::Endometrial carcinoma (EC) is the most common malignant tumors in female derived from the endometrial epithelium. Several previous studies have described estrogen receptors (ER), progesterone Receptor (PR) and phosphatase and tensin homolog (PTEN) are associated with clinicopathological factors and prognosis in EC pat...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.33720
更新日期:2020-01-13 00:00:00
abstract::To explore the role of phospholipase D1 (PLD1) mRNA in transition of prostate cancer (PCa) cells to androgen independence, we used Arraystar Human LncRNA Microarray V3.0 to detect and compare the differential expression of PLD1 and its signaling pathway-related gene in standard androgen dependence prostate cancer (ADP...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.26689
更新日期:2018-09-08 00:00:00
abstract:BACKGROUND:Non-small cell lung cancer (NSCLC) accounts for approximately 85% of clinical lung cancer cases. MicroRNA-93 (miR-93) is an oncomiR in many types of human cancer, exerting pivotal effects in the development and progression of malignancies, including NSCLC. However, the mechanism underlying miR-93 involvement...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.17958
更新日期:2017-03-07 00:00:00
abstract::Hepatocellular carcinoma (HCC) is a major malignancy of cancer-related mortality worldwide. Metastasis-associated in colon cancer-1 (MACC1) was suggested as a marker for vascular invasive HCC. This study investigated the MACC1 single-nucleotide polymorphisms (SNPs) to evaluate HCC susceptibility and clinicopathologica...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.38856
更新日期:2020-01-14 00:00:00
abstract::Purpose: Systemic therapy has often been used for patients with advanced hepatocellular carcinoma (HCC). However, due to drug resistance, the use of cytotoxic chemotherapy in the treatment of patients with advanced HCC has typically demonstrated low response rates. Secretory clusterin (sCLU) is expressed in aggressive...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.23849
更新日期:2018-04-06 00:00:00
abstract:PURPOSE:Urothelial carcinoma (UC) is a type of tumor, especially of the urinary bladder, that affects people worldwide. Clarification of its detailed tumor biology and discovery of potential targets for developing treatment strategies are imperative because of frequent recurrences and poor prognosis of advanced UCs. By...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.15696
更新日期:2016-07-08 00:00:00
abstract::Background: Proverbially, the incidence rate of papillary thyroid carcinoma (PTC) has increased year by year. Many long noncoding RNAs (lncRNAs) have been discovered having a relationship with tumor genesis tightly recently. Thanks to the previous researches, we found long intergenic noncoding RNA 00511 (LINC00511) is...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.35364
更新日期:2020-01-01 00:00:00
abstract::Background: Colorectal cancer (CRC) remains to be one of the most common malignancies worldwide. Various studies have demonstrated that microRNAs (miRs) play a critical role in regulating cancer progression and sensitivity to chemoradiotherapy. miR-1 was found to be aberrantly expressed in CRC. However, it has not bee...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.44753
更新日期:2020-06-07 00:00:00
abstract:OBJECTIVES:To study whether radical nephrectomy (RN) with lymph node dissection (LND) can benefit pT3 renal cell carcinoma (RCC) patients versus no LND under the 2018 American Joint Committee on Cancer TNM classification system. Subjects/Patients and Methods: We performed a retrospective cohort study of clinicopatholog...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.30375
更新日期:2019-05-26 00:00:00
abstract::Transarterial chemoembolization (TACE) has been considered the standard treatment for intermediate-stage hepatocellular carcinoma according to BCLC algorithm. However, it has been unclear about the TACE-related predictive bio-markers and underlying molecular mechanisms. This investigation revealed that HCCs with highe...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.35631
更新日期:2020-01-01 00:00:00
abstract::Stromal fibroblasts are suggested to be a key determinant in the malignant progression of breast cancer. To find an in vitro culture model that best mimics the in vivo tumor microenvironment so we can study the effects of stromal fibroblasts on breast cancer progression, we evaluated several three-dimensional (3D) co-...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.2.458
更新日期:2011-01-01 00:00:00