Everolimus following 5-aza-2-deoxycytidine is a promising therapy in paclitaxel-resistant clear cell carcinoma of the ovary.

Abstract:

:Our previous study showed that 5-aza-2-deoxycytidine (5-aza-dC) could inhibit tumor growth by enhancing the susceptibility of ovarian clear cell carcinoma (OCCC) to paclitaxel through decreasing AKT/mTOR expressions. The objective of the study is to evaluate the antitumor efficacy of everolimus (RAD001) and 5-aza-2-deoxycytidine (5-aza-dC) by targeting AKT/mTOR and EZH2 in OCCC. Paclitaxel-sensitive and resistant OCCC cell lines were established. In vitro proliferative and apoptotic assays and flow cytometry were performed. The expressions of EZH2, PIK3IP1, phospho-AKT, phospho-mTOR and phospho-Rictor in the OCCC cell lines were evaluated by Western blotting. In vivo animal experiments with RAD001 and 5-aza-dC were performed. RAD001 alone showed significant in vitro antitumor activity and inhibited in vivo tumor growth in paclitaxel-sensitive and resistant OCCC cells. In addition, 5-aza-dC enhanced the antitumor effects when combined with paclitaxel or RAD001 in both paclitaxel-sensitive and resistant tumors. Activation of phospho-AKT ser473 and PIK3IP1 was observed in RAD001-treated paclitaxel-sensitive and resistant OCCC cells. In contrast, inhibition of phospho-AKT ser473 and EZH2 was observed with RAD001 following 5-aza-dC treatment of paclitaxel-sensitive and resistant OCCC cells. Furthermore, RAD001 following 5-aza-dC enhanced apoptosis of paclitaxel-sensitive and resistant OCCC cells. RAD001 following 5-aza-dC may be a promising treatment strategy for the treatment of both chemo-sensitive and resistant OCCC. Further clinical studies are warranted.

journal_name

Am J Cancer Res

authors

Ho CM,Lee FK,Huang SH,Cheng WF

subject

Has Abstract

pub_date

2018-01-01 00:00:00

pages

56-69

issue

1

issn

2156-6976

journal_volume

8

pub_type

杂志文章
  • Elevated RABEX-5 expression predicts poor prognosis in non-small-cell lung cancer.

    abstract::RABEX-5 has been studied in various solid tumors, but its role in non-small-cell lung cancer (NSCLC) remains unknown. This study is aimed to investigate the expression, the potential relevance to clinicopathological characters and prognostic significance of RABEX-5 in patients with NSCLC. A total of 120 NSCLC patients...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Zhang F,Jia Y,Kong F,Hu G,Cai Q,Xu T

    更新日期:2015-08-15 00:00:00

  • Profile of differentially expressed intratumoral cytokines to predict the immune-polarizing side effects of tamoxifen in breast cancer treatment.

    abstract::Factors within the tissue of breast cancer (BC) may shift the polarization of CD4+ T cells towards Th2 direction. This tendency can promote tumor development and be enhanced by the use of tamoxifen during the treatment. Thus, the patients with low levels of tumor-induced Th2 polarization prior to tamoxifen treatment m...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Li B,Li Y,Wang XY,Yan ZQ,Liu H,Liu GR,Liu SL

    更新日期:2015-01-15 00:00:00

  • LncRNA, a novel target biomolecule, is involved in the progression of colorectal cancer.

    abstract::Colorectal cancer is one of the most commonly diagnosed malignancies among males and females worldwide. Although China is a country with a low incidence of colorectal cancer, with the improvement of China's economy and lifestyle changes, the incidence rate in China has generally increased in recent years, and the morb...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Sun W,Ren S,Li R,Zhang Q,Song H

    更新日期:2019-11-01 00:00:00

  • Analysis of difference of association between polymorphisms in the XRCC5, RPA3 and RTEL1 genes and glioma, astrocytoma and glioblastoma.

    abstract:BACKGROUND:Gliomas are the most common aggressive brain tumors and have many complex pathological types. Previous reports have discovered that genetic mutations are associated with the risk of glioma. However, it is unclear whether uniform genetic mutations exist difference between glioma and its two pathological types...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Jin T,Wang Y,Li G,Du S,Yang H,Geng T,Hou P,Gong Y

    更新日期:2015-06-15 00:00:00

  • Molecular dynamics simulation on the low sensitivity of mutants of NEDD-8 activating enzyme for MLN4924 inhibitor as a cancer drug.

    abstract::MLN4924 is an experimental cancer drug known as inhibitor of NEDD8-activating enzyme (NAE). This anti-tumor candidate is a selective small-molecule inhibitor of NAE which is conjugated to cullin protein on Cullin-RING ligases (CRLs). This covalent modification actives cullin complex to recruit an ubiquitin-charged E2 ...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Rashidieh B,Valizadeh M,Assadollahi V,Ranjbar MM

    更新日期:2015-10-15 00:00:00

  • MiR-449a suppresses cell invasion by inhibiting MAP2K1 in non-small cell lung cancer.

    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:

    authors: You J,Zhang Y,Li Y,Fang N,Liu B,Zu L,Zhou Q

    更新日期:2015-08-15 00:00:00

  • ALDH2 modulates autophagy flux to regulate acetaldehyde-mediated toxicity thresholds.

    abstract::A polymorphic mutation in the acetaldehyde dehydrogenase 2 (ALDH2) gene has been epidemiologically linked to the high susceptibility to esophageal carcinogenesis for individuals with alcohol use disorders. Mice subjected to alcohol drinking show increased oxidative stress and DNA adduct formation in esophageal epithel...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Tanaka K,Whelan KA,Chandramouleeswaran PM,Kagawa S,Rustgi SL,Noguchi C,Guha M,Srinivasan S,Amanuma Y,Ohashi S,Muto M,Klein-Szanto AJ,Noguchi E,Avadhani NG,Nakagawa H

    更新日期:2016-03-15 00:00:00

  • Muc1 promotes migration and lung metastasis of melanoma cells.

    abstract::Early stages of melanoma can be successfully treated by surgical resection of the tumor, but there is still no effective treatment once it is progressed to metastatic phases. Although growing family of both melanoma metastasis promoting and metastasis suppressor genes have been reported be related to metastasis, the m...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Wang X,Lan H,Li J,Su Y,Xu L

    更新日期:2015-08-15 00:00:00

  • Long noncoding RNA CASC11 promotes osteosarcoma metastasis by suppressing degradation of snail mRNA.

    abstract::Osteosarcoma (OS) is the most common primary bone tumor in adolescents. Dysregulation of long noncoding RNAs (lncRNAs) is associated with the cancer progression, of which cancer susceptibility candidate 11 (CASC11) has been indicated as an oncogene in several human cancers. However, the underlying mechanisms by which ...

    journal_title:American journal of cancer research

    pub_type: 杂志文章,收录出版

    doi:

    authors: Song K,Yuan X,Li G,Ma M,Sun J

    更新日期:2019-02-01 00:00:00

  • DNA integrity as biomarker in pancreatic cyst fluid.

    abstract::Identification of pancreatic cysts with malignant potential is important to prevent pancreatic cancer development. Integrity of cell free DNA (cfDNA) has been described as tumor biomarker, but its potential for pancreatic cancer is unclear. While normal apoptotic cells release uniformly truncated DNA, malignant tissue...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Utomo WK,Janmaat VT,Verhaar AP,Cros J,Lévy P,Ruszniewski P,den Berg MS,Jenster G,Bruno MJ,Braat H,Fuhler GM,Peppelenbosch MP

    更新日期:2016-08-01 00:00:00

  • Erratum: Heat shock protein 70-2 (HSP70-2) a novel cancer testis antigen that promotes growth of ovarian cancer.

    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:

    authors: Gupta N,Jagadish N,Surolia A,Suri A

    更新日期:2020-06-01 00:00:00

  • Combined efficacy and mechanism of trifluridine and SN-38 in a 5-FU-resistant human colorectal cancer cell lines.

    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:

    authors: Matsuoka K,Takechi T

    更新日期:2017-12-01 00:00:00

  • Expression profiles analysis identifies a novel three-mRNA signature to predict overall survival in oral squamous cell carcinoma.

    abstract::Oral squamous cell carcinoma (OSCC) remains to be a challenging public health problem worldwide. However, the underlying molecular mechanism regulating the carcinogenesis of OSCC is poorly known. Gene expression profiles of GSE13601, GSE30784, GSE37991 and The Cancer Genome Atlas (TCGA) head and neck cancer were downl...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Zhao X,Sun S,Zeng X,Cui L

    更新日期:2018-03-01 00:00:00

  • METTL3 plays multiple functions in biological processes.

    abstract::N6-methyladenosine (m6A) is the most common internal modification of mRNAs in higher eukaryotic. This process is performed by methyltransferase. Methyltransferase-like 3 (METTL3) is the best known m6A methyltransferase that functions in the reversible epi-transcriptome modulation of m6A modification. Besides acting as...

    journal_title:American journal of cancer research

    pub_type: 杂志文章,评审

    doi:

    authors: Liu S,Zhuo L,Wang J,Zhang Q,Li Q,Li G,Yan L,Jin T,Pan T,Sui X,Lv Q,Xie T

    更新日期:2020-06-01 00:00:00

  • MicroRNA-1301 inhibits proliferation of human glioma cells by directly targeting N-Ras.

    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:

    authors: Zhi T,Jiang K,Zhang C,Xu X,Wu W,Nie E,Yu T,Zhou X,Bao Z,Jin X,Zhang J,Wang Y,Liu N

    更新日期:2017-04-01 00:00:00

  • Overexpression of MEF2D contributes to oncogenic malignancy and chemotherapeutic resistance in ovarian carcinoma.

    abstract::The transcription factor MEF2 promotes survival in various cell types and a number of studies indicate that abnormal regulation of MEF2 is linked to oncogenicity in several carcinomas. We have found that MEF2D, a member of the MEF2 family, is upregulated in Ovarian Cancer (OC). Immunohistochemistry analysis of tumor s...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Li X,Zhang Y,Chai X,Zhou S,Zhang H,He J,Zhou R,Cai L,Chen L,Tao G

    更新日期:2019-05-01 00:00:00

  • Hispidulin suppresses tumor growth and metastasis in renal cell carcinoma by modulating ceramide-sphingosine 1-phosphate rheostat.

    abstract::Sphingosine 1-phosphate (S1P) rheostat is considered as a key signal that determines cell fate. This study aimed to report that hispidulin, a polyphenolic flavonoid, exerted anti-growth and anti-metastasis effects against renal cell carcinoma (RCC) by modulating the balance of ceramide-S1P. In vitro studies showed tha...

    journal_title:American journal of cancer research

    pub_type: 杂志文章,收录出版

    doi:

    authors: Gao MQ,Gao H,Han M,Liu KL,Peng JJ,Han YT

    更新日期:2017-07-01 00:00:00

  • Over expression of hyaluronan promotes progression of HCC via CD44-mediated pyruvate kinase M2 nuclear translocation.

    abstract::Hyaluronan is expressed in hepatocellular carcinoma (HCC) as HCC generally arises from a cirrhotic liver in which excessive production and accumulation of HA leads to developing cirrhosis. Though it has been suggested HA is involved in progression of HCC, the mechanisms underlying the connection between HA and HCC pro...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Li JH,Wang YC,Qin CD,Yao RR,Zhang R,Wang Y,Xie XY,Zhang L,Wang YH,Ren ZG

    更新日期:2016-01-15 00:00:00

  • Stromal modulation of bladder cancer-initiating cells in a subcutaneous tumor model.

    abstract::The development of new cancer therapeutics would benefit from incorporating efficient tumor models that mimic human disease. We have developed a subcutaneous bladder tumor regeneration system that recapitulates primary human bladder tumor architecture by recombining benign human fetal bladder stromal cells with SW780 ...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Peek EM,Li DR,Zhang H,Kim HP,Zhang B,Garraway IP,Chin AI

    更新日期:2012-01-01 00:00:00

  • Depletion of gamma-glutamylcyclotransferase in cancer cells induces autophagy followed by cellular senescence.

    abstract::Gamma-glutamylcyclotransferase (GGCT) was originally identified as a protein highly expressed in bladder cancer tissues by proteomic analysis, and its higher expression in a variety of cancers compared to normal tissues have been shown. Depletion of GGCT in various cancer cells results in antiproliferative effects bot...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Taniguchi K,Matsumura K,Ii H,Kageyama S,Ashihara E,Chano T,Kawauchi A,Yoshiki T,Nakata S

    更新日期:2018-04-01 00:00:00

  • Docosahexaenoic acid (DHA), an omega-3 fatty acid, inhibits tumor growth and metastatic potential of ovarian cancer.

    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:

    authors: West L,Yin Y,Pierce SR,Fang Z,Fan Y,Sun W,Tucker K,Staley A,Zhou C,Bae-Jump V

    更新日期:2020-12-01 00:00:00

  • Chiauranib selectively inhibits colorectal cancer with KRAS wild-type by modulation of ROS through activating the p53 signaling pathway.

    abstract::Colorectal cancer (CRC) is one of the top three most deadly cancers despite using chemotherapy based on oxaliplatin or irinotecan combined with targeted therapy. Chiauranib has recently been identified to be a promising anticancer candidate with impressive efficacy and safety. However, the role and molecular mechanism...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Yin H,Xie J,Jiang P,Jiang X,Duan D,Qi J,Luo Z,Ma C,Hong H

    更新日期:2020-11-01 00:00:00

  • Genetic variants of BCL2 gene predict clinical outcomes of non-small-cell lung cancer patients treated with platinum-based chemotherapy in a Chinese population.

    abstract::Platinum agents induce cancer cell death through BCL2-dependent intrinsic apoptotic pathway and are commonly used as anti-tumor drug. In this study, we evaluated whether single nucleotide polymorphism (SNPs) of BCL2 can affect the overall survival (OS) and progression-free survival (PFS) in non-small-cell lung cancer ...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Ding X,Qian J,Yang Y,Xu W,Liu D,Su B

    更新日期:2016-10-01 00:00:00

  • Polycomb protein family member CBX7 plays a critical role in cancer progression.

    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:

    authors: Pallante P,Forzati F,Federico A,Arra C,Fusco A

    更新日期:2015-04-15 00:00:00

  • Does the expression of BCL2 have prognostic significance in malignant peritoneal mesothelioma?

    abstract:UNLABELLED:Background Malignant peritoneal mesothelioma (MPM) is a rare neoplasm of the peritoneal membrane that is causally related to asbestos exposure. Survival after treatment is poor. Current therapy involving hyperthermic intraperitoneal chemotherapy has improved survival in selective patients. In the past, sever...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Pillai K,Pourgholami MH,Chua TC,Morris DL

    更新日期:2013-06-20 00:00:00

  • PCOS and obesity: insulin resistance might be a common etiology for the development of type I endometrial carcinoma.

    abstract::Endometrial cancer (EC) is the most common gynecological malignancy in women and is the leading cause of cancer-related deaths worldwide. Estrogenic stimulation significantly increases endometrial cell proliferation, and both insulin resistance and hyperinsulinemia are associated with the development of EC in women. I...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Li X,Shao R

    更新日期:2014-01-15 00:00:00

  • SLFN5 influences proliferation and apoptosis by upregulating PTEN transcription via ZEB1 and inhibits the purine metabolic pathway in breast cancer.

    abstract::Human Schlafen-5 (SLFN5) is aberrantly involved in tumorigenesis in several types of cancer. However, its implications in breast cancer (BRCA) are unknown. Herein, we demonstrated that SLFN5 expression is negatively associated with the tumour growth of human BRCA using GEO database analysis and clinical sample immunos...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Gu X,Wan G,Yang Y,Liu Y,Yang X,Zheng Y,Jiang L,Zhang P,Liu D,Zhao W,Huang G,Lu C

    更新日期:2020-09-01 00:00:00

  • Afatinib down-regulates MCL-1 expression through the PERK-eIF2α-ATF4 axis and leads to apoptosis in head and neck squamous cell carcinoma.

    abstract::Afatinib is the second generation of irreversible inhibitor of EGFR, HER2 and HER4, which has shown encouraging phase II and III clinical outcomes in the treatment of head and neck squamous cell carcinoma (HNSCC). However, the molecular mechanism of afatinib-induced apoptosis in HNSCC is poorly understood. In the pres...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Liu X,Lv Z,Zou J,Liu X,Ma J,Wang J,Sa N,Jing P,Xu W

    更新日期:2016-08-01 00:00:00

  • Hypoxia regulates SOX2 expression to promote prostate cancer cell invasion and sphere formation.

    abstract::SOX2 is an embryonic stem cell marker that in prostate cancer has been associated not only with tumorigenesis but also metastasis. Furthermore hypoxia in primary tumors has been linked to poor prognosis and outcomes in this disease. The goal of the present study was to investigate the impact of hypoxia on SOX2 express...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Bae KM,Dai Y,Vieweg J,Siemann DW

    更新日期:2016-05-01 00:00:00

  • DcR3 promotes proliferation and invasion of pancreatic cancer via a DcR3/STAT1/IRF1 feedback loop.

    abstract::Pancreatic cancer (PC) is one of the most common gastrointestinal malignancies that are highly aggressive with a low 5-year survival rate. Accumulated evidence has indicated that decoy receptor 3 (DcR3) is involved in several pathologic processes and various cancers. However, the mechanisms underlying dysregulated DcR...

    journal_title:American journal of cancer research

    pub_type: 杂志文章

    doi:

    authors: Wei Y,Chen X,Yang J,Yao J,Yin N,Zhang Z,Li D,Zhu D,Zhou J

    更新日期:2019-12-01 00:00:00