Upregulated NOX1 expression in gallbladder cancer‑associated fibroblasts predicts a poor prognosis.

Abstract:

:Gallbladder cancer (GBC) is a lethal aggressive malignant neoplasm of the biliary tract. Potential prognostic markers and therapeutic targets for this disease are urgently required. Cancer‑associated fibroblasts (CAFs) play a key role in tumorigenesis and the development of cancer. Nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1) expression has been reported to be involved in tumorigenesis and useful for tumor prognosis. However, NOX1 expression in the stroma of GBCs, particularly gallbladder cancer‑associated fibroblasts (GCAFs), and its prognostic significance in GBC patients remains unclear. In the present study, NOX1 expression in the stroma of human gallbladder lesions in vivo was investigated, as well as in GCAFs and co‑cultures of GBC‑SD+GCAFs in vitro, and their correlation with clinicopathological parameters and the prognosis of GBC patients were evaluated. The results revealed that NOX1 expression was significantly upregulated in the stroma of GBCs compared with precancerous and benign lesions of the gallbladder; NOX1 expression was localized to gallbladder stromal fibroblasts expressing α‑smooth muscle actin and fibroblast secreted protein‑1. Furthermore, these observations were confirmed by the fact that NOX1 expression was upregulated in GCAFs as determined by Affymetrix gene profile chip analysis and reverse transcription‑quantitative PCR. In addition, overexpression was observed in formed spheroids of GBC‑SD+GCAF co‑cultures by immunohistochemistry and western blotting in vitro. Thus, it was verified that NOX1 expression was upregulated in GCAFs. Furthermore, upregulated stromal NOX1 expression was correlated with aggressive characteristics such as differentiation degree (P=0.042), venous invasion (P=0.041), resection methods (P=0.002), and a lower survival rate (P=0.025, log‑rank test) of patients with GBC. Stromal NOX1 expression (P=0.047) was an independent prognostic factor for the overall survival rate of patients with GBC. GBC patients with upregulated NOX1 expression in GCAFs had a poorer prognosis. These results revealed that stromal NOX1 may be a novel biomarker and/or target, and may contribute to the discovery of new tumor markers and potential targeted therapeutics for human GBCs.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Wang FT,Hassan M,Ansari KH,Xu GL,Li XP,Fan YZ

doi

10.3892/or.2019.7249

subject

Has Abstract

pub_date

2019-10-01 00:00:00

pages

1475-1486

issue

4

eissn

1021-335X

issn

1791-2431

journal_volume

42

pub_type

杂志文章
  • The antitumor effect of human cord blood-derived dendritic cells modified by the livin α gene in lung cancer cell lines.

    abstract::The growth of malignant tumors is associated with mechanisms of immune escape and inhibition of apoptosis. Livin is a novel member of the inhibitors of apoptosis (IAP) protein family that inhibits cell apoptosis. Livin is specifically expressed by the majority of tumor cells, but it is not expressed in normal adult ti...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2012.2133

    authors: Chen H,Jin Y,Chen T,Zhang M,Ma W,Xiong X,Tao X

    更新日期:2013-02-01 00:00:00

  • Expression of miRNA-146a in nasopharyngeal carcinoma is upregulated by Epstein-Barr virus latent membrane protein 1.

    abstract::We aimed to investigate the relationship between miRNA-146a and latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) in nasopharyngeal carcinoma (NPC). The expression levels of LMP1 in 40 cases of NPC, 28 cases of chronic nasopharyngitis and NPC cell lines CNE1 and CNE1-GL (...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2012.1933

    authors: Zhao Y,Chen X,Jing M,Du H,Zeng Y

    更新日期:2012-10-01 00:00:00

  • Tumor-suppressive mir-663 gene induces mitotic catastrophe growth arrest in human gastric cancer cells.

    abstract::Increasing evidence suggests that microRNAs are involved in human carcinogenesis as tumor suppressors or oncogenes. A growing number of reports has shown that an interest has been sparked in aberrant microRNA expression and how they can be used to treat human diseases, including cancer. However, their precise biologic...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or_00000834

    authors: Pan J,Hu H,Zhou Z,Sun L,Peng L,Yu L,Sun L,Liu J,Yang Z,Ran Y

    更新日期:2010-07-01 00:00:00

  • Differentiation of benign and malignant breast tumors using Doppler spectral parameters including acceleration time index.

    abstract::Differentiation of breast cancer has been receiving increasing attention in attempts to minimize the numbers of excisional biopsies for benign tumors. Doppler spectral parameters, such as peak systolic velocity (PSV) and pulsatility index (PI), have been used but these are unable to differentiate breast cancers and be...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Mesaki K,Hisa N,Kubota K,Hisa N,Ogawa Y,Yoshida S

    更新日期:2003-07-01 00:00:00

  • miR-182 promotes cell growth and invasion by targeting forkhead box F2 transcription factor in colorectal cancer.

    abstract::Forkhead box F2 transcription factor (FoxF2) has been described to promote organ development, extracellular matrix (ECM) synthesis and epithelial-mesenchymal interaction. Although recent studies reported decreased FoxF2 expression in several types of cancers, indicating its potential role in carcinogenesis, the mechan...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.3833

    authors: Zhang Y,Wang X,Wang Z,Tang H,Fan H,Guo Q

    更新日期:2015-05-01 00:00:00

  • PTEN-positive and phosphorylated-Akt-negative expression is a predictor of survival for patients with advanced endometrial carcinoma.

    abstract::PTEN and the PI3K/Akt pathway are involved in the development and/or progression of endometrial carcinoma. To clarify the impact of the pathway-related molecules on prognosis, we analyzed PTEN, phosphorylated-Akt (p-Akt), and Ki-67 expression by immunohistochemistry in 99 patients with advanced endometrial carcinoma. ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Uegaki K,Kanamori Y,Kigawa J,Kawaguchi W,Kaneko R,Naniwa J,Takahashi M,Shimada M,Oishi T,Itamochi H,Terakawa N

    更新日期:2005-08-01 00:00:00

  • Changes in bone resorption and vascular endothelial growth factor after a single zoledronic acid infusion in cancer patients with bone metastases from solid tumours.

    abstract::Zoledronic acid (Zometa, ZOL) is increasingly used to treat tumour-induced bone disease, and is also reported to have antiangiogenic properties in vivo. In this study, we have investigated the correlations between changes in the proangiogenic cytokine, vascular endothelial growth factor (VEGF), and markers of bone res...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Santini D,Vincenzi B,Hannon RA,Brown JE,Dicuonzo G,Angeletti S,La Cesa A,Coleman RE,Tonini G,Budillon A,Caraglia M,Holen I

    更新日期:2006-05-01 00:00:00

  • Increased expression and activity of p75NTR are crucial events in azacitidine-induced cell death in prostate cancer.

    abstract::The high affinity nerve growth factor (NGF) NGF receptor, p75NTR, is a member of the tumor necrosis factor (TNF) receptor superfamily that shares a conserved intracellular death domain capable of inducing apoptosis and suppressing growth in prostate epithelial cells. Expression of this receptor is lost as prostate can...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.4832

    authors: Gravina GL,Marampon F,Sanità P,Mancini A,Colapietro A,Scarsella L,Jitariuc A,Biordi L,Ficorella C,Festuccia C

    更新日期:2016-07-01 00:00:00

  • Inhibition of CCR7 promotes NF-κB-dependent apoptosis and suppresses epithelial-mesenchymal transition in non-small cell lung cancer.

    abstract::Activation of C-C chemokine receptor type 7 (CCR7) has been demonstrated to mediate the occurrence and progression of non-small cell lung cancer (NSCLC). However, the potential therapeutic role of CCR7 inhibition in NSCLC is still obscure. Thus, the present study was conducted to investigate the molecular mechanism un...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2017.5524

    authors: Zhang L,Xiao X,An H,Wang J,Ma Y,Qian YH

    更新日期:2017-05-01 00:00:00

  • Predictive factors in patients with advanced and metastatic squamous cell carcinoma of the head and neck: a study based on SWOG protocol S0420.

    abstract::To evaluate the prognostic values of different protein expression in the progression of squamous cell carcinoma of the head and neck (SCCHN) patients, we conducted immunohistochemical (IHC) analysis in tissue samples of different patients enrolled on SWOG protocol S0420. S0420 was a phase II trial to evaluate the effi...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2374

    authors: Mehta S,Moon J,Hashmi M,Leblanc M,Huang CH,Rinehart E,Wolf GT,Urba SG,Banerjee SK,Williamson S

    更新日期:2013-06-01 00:00:00

  • Triptolide induced DNA damage in A375.S2 human malignant melanoma cells is mediated via reduction of DNA repair genes.

    abstract::Numerous studies have demonstrated that triptolide induces cell cycle arrest and apoptosis in human cancer cell lines. However, triptolide-induced DNA damage and inhibition of DNA repair gene expression in human skin cancer cells has not previously been reported. We sought the effects of triptolide on DNA damage and a...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2012.2170

    authors: Chueh FS,Chen YL,Hsu SC,Yang JS,Hsueh SC,Ji BC,Lu HF,Chung JG

    更新日期:2013-02-01 00:00:00

  • Effects of low-intensity ultrasound combined with low-dose carboplatin in an orthotopic hamster model of tongue cancer: A preclinical study.

    abstract::Low-intensity ultrasound (LIUS) combined with chemotherapy is an innovative modality for cancer treatment, but its effect on orthotopic carcinoma remains unknown. Our previous study revealed that LIUS enhanced the growth inhibitory effects of several chemotherapeutic drugs in nude mice with transplanted tumors. In the...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2018.6262

    authors: Li HX,Zheng JH,Ji L,Liu GY,Lv YK,Yang D,Hu Z,Chen H,Zhang FM,Cao W

    更新日期:2018-04-01 00:00:00

  • Metastasis-associated protein 1 inhibits p53-induced apoptosis.

    abstract::Metastasis-associated protein 1 (MTA1) is highly upregulated in cancer cells with metastatic potential; however, the molecular mechanism by which MTA1 increases the metastatic potential of cancer cells is far from clear. We characterized the functional consequences of MTA1 overexpression on p53-induced apoptosis of ca...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Moon HE,Cheon H,Lee MS

    更新日期:2007-11-01 00:00:00

  • PBOV1 correlates with progression of ovarian cancer and inhibits proliferation of ovarian cancer cells.

    abstract::Prostate and breast cancer overexpressed 1 (PBOV1) is significantly upregulated in prostate, breast and bladder cancer, while its expression status in ovarian cancer and its clinical significance are unclear. We examined the expression levels of PBOV1 mRNA and protein in ovarian cancer cell lines and primary tissues u...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4396

    authors: Wang L,Niu CH,Wu S,Wu HM,Ouyang F,He M,He SY

    更新日期:2016-01-01 00:00:00

  • Anti-oxidative and hepatoprotective effects of lithospermic acid against carbon tetrachloride-induced liver oxidative damage in vitro and in vivo.

    abstract::Accumulation of an excess amount of reactive oxygen species (ROS) can cause hepatotoxicity that may result in liver damage. Therefore, development of anti-oxidative agents is needed for reducing liver toxicity. This study investigated the anti-oxidative and hepatoprotective activity of lithospermic acid, a plant-deriv...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4068

    authors: Chan KW,Ho WS

    更新日期:2015-08-01 00:00:00

  • The usefulness and limits of magnetic resonance imaging in the differential diagnosis of pelvic tumors.

    abstract::Three cases of benign pelvic tumors are presented (2 leiomyomas and 1 fibroma). All three tumors were suspected of being malignant neoplasms because they were visualized as heterogeneous high signal intensity on T2-weighted images, and thus they were difficult to diagnose preoperatively. One of the leiomyomas was loca...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.8.4.867

    authors: Kojima T,Ishiko O,Ichimura T,Nishimura S,Sumi T,Ueda J,Tsujimura T,Shimura K

    更新日期:2001-07-01 00:00:00

  • Inhibition of endoplasmic reticulum stress-induced autophagy sensitizes melanoma cells to temozolomide treatment.

    abstract::The incidence of malignant melanoma is increasing. The discovery of agents specifically targeting the mutated cascades has provided a good response for patients with oncogenic B-Raf proto-оncogene, serine/threonine kinase (BRAF). However, numerous studies continue to focus on novel methods of treatment to overcome acq...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2018.6430

    authors: Ryabaya O,Prokofieva A,Khochenkov D,Abramov I,Zasedatelev A,Stepanova E

    更新日期:2018-07-01 00:00:00

  • miR-24-3p regulates bladder cancer cell proliferation, migration, invasion and autophagy by targeting DEDD.

    abstract::microRNAs (miRNAs), a class of small non-coding RNA molecules, can regulate gene expression by interacting with the 3'-untranslated regions (3'UTR) of target genes and influence various biological processes. We investigated the potential role of miR-24-3p in the development of bladder cancer by regulating DEDD, a memb...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.5326

    authors: Yu G,Jia Z,Dou Z

    更新日期:2017-02-01 00:00:00

  • DNA methylation and histone modifications as epigenetic regulation in prostate cancer (Review).

    abstract::Prostate cancer is the second most commonly diagnosed cancer in men in Poland after lung cancer and the third leading cause of cancer-related mortality after lung and colon cancer. The etiology of most cases of prostate cancer are not fully known, and therefore it is essential to search for the molecular basis of pros...

    journal_title:Oncology reports

    pub_type: 杂志文章,评审

    doi:10.3892/or.2017.5972

    authors: Nowacka-Zawisza M,Wiśnik E

    更新日期:2017-11-01 00:00:00

  • Combination treatment with proteasome inhibitors and antiestrogens has a synergistic effect mediated by p21WAF1 in estrogen receptor-positive breast cancer.

    abstract::Although antiestrogens significantly improve the survival of patients with ER-positive breast cancer, therapeutic resistance remains a major limitation. The combinatorial use of antiestrogen with other therapies was proposed to increase their efficiency and more importantly, to prevent or delay the resistance phenomen...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.4873

    authors: Maynadier M,Basile I,Gallud A,Gary-Bobo M,Garcia M

    更新日期:2016-08-01 00:00:00

  • Analysis of caspase activities in rat mammary tumours induced by N-methyl-nitrosourea.

    abstract::Normal breast development is controlled by a balance between cell proliferation and apoptosis. The balance between the two parameters is crucial for determining the growth or regression of breast tumours in response to therapies and treatments. Therefore, it is necessary to understand the role of apoptosis in tumour p...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Puertollano MA,Carrera MP,Puertollano E,Alvarez de Cienfuegos G,Ramirez-Expósito MJ,De Pablo MA,Martinez-Martos JM

    更新日期:2008-09-01 00:00:00

  • In vivo antitumor effect of ascorbic acid, lysine, proline and green tea extract on human colon cancer cell HCT 116 xenografts in nude mice: evaluation of tumor growth and immunohistochemistry.

    abstract::Colorectal cancer is the second most deadly cancer in the United States. When diagnosed early, current treatments bring a limited success; however, once metastasis occurs, radiation and chemotherapy are generally ineffective. Structural changes in the ECM are necessary for cell migration during tissue remodeling. Matr...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Roomi MW,Ivanov V,Kalinovsky T,Niedzwiecki A,Rath M

    更新日期:2005-03-01 00:00:00

  • Withaferin A inhibits matrix metalloproteinase-9 activity by suppressing the Akt signaling pathway.

    abstract::Withaferin A (Wit A), a steroidal lactone isolated from Withania somnifera, exhibits anti-inflammatory, immuno-modulatory and anti-angiogenic properties and antitumor activities. In the present study, we investigated the effects of Wit A on protease-mediated invasiveness of the human metastatic cancer cell lines Caski...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2487

    authors: Lee DH,Lim IH,Sung EG,Kim JY,Song IH,Park YK,Lee TJ

    更新日期:2013-08-01 00:00:00

  • Effect of combining anti-epidermal growth factor receptor antibody C225 and radiation on DU145 prostate cancer.

    abstract::The epidermal growth factor receptor (EGFR) network has rich targets for prostate cancer killing. Herein we evaluated the effects of combining the EGFR inhibition and radiation on DU145 prostate cancer. We treated DU145 prostate cancer cells with various doses of anti-EGFR antibody (C225) and gamma-irradiation (RAD). ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Wagener M,Zhang X,Villarreal HG,Levy L,Allen P,Shentu S,Fang B,Krishnan S,Chang JY,Cheung MR

    更新日期:2008-05-01 00:00:00

  • PSMB4 overexpression enhances the cell growth and viability of breast cancer cells leading to a poor prognosis.

    abstract::PSMB4, proteasome subunit β4, is a member of the ubiquitin-proteasome family, and is elevated in a variety of malignancies. However, the expression level and related mechanism of PSMB4 in breast cancer remains unclear. Therefore, the present study investigated the expression level of PSMB4 in eight pairs of breast can...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2018.6588

    authors: Wang H,He Z,Xia L,Zhang W,Xu L,Yue X,Ru X,Xu Y

    更新日期:2018-10-01 00:00:00

  • Polysaccharide from Inonotus obliquus inhibits migration and invasion in B16-F10 cells by suppressing MMP-2 and MMP-9 via downregulation of NF-κB signaling pathway.

    abstract::Polysaccharides derived from Inonotus obliquus (PIO) are known to possess multiple pharmacological activities including antitumor activity. However, the possible molecular mechanisms of these activities are unknown. In the present study, we determined the anti-metastatic potential and signaling pathways of PIO in the ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2014.3103

    authors: Lee KR,Lee JS,Kim YR,Song IG,Hong EK

    更新日期:2014-05-01 00:00:00

  • HSG provides antitumor efficacy on hepatocellular carcinoma both in vitro and in vivo.

    abstract::Hyperplasia suppressor gene (HSG) is a novel gene that markedly suppresses the mitogenetic stimuli or injury mediated by vascular smooth muscle cell proliferation. Herein we provide experimental evidence to show that HSG can also play a key role in tumor proliferation. Down-regulation of HSG protein in hepatocellular ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Wang W,Zhu F,Wang S,Wei J,Jia C,Zhang Y,Zhou L,Xie H,Zheng S

    更新日期:2010-07-01 00:00:00

  • Antitumor activities of dFv-LDP-AE: An enediyne-energized fusion protein targeting tumor-associated antigen gelatinases.

    abstract::Gelatinases play an important role in tumor growth and metastasis, and overexpression of these molecules is strongly correlated with poor prognosis in a variety of malignant tumors. Lidamycin is an enediyne antitumor antibiotic with potent cytotoxicity. We previously reported that a...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2012.1910

    authors: Zhong GS,Wu MN,Guo XF,Zhang SH,Miao QF,Zhen YS

    更新日期:2012-10-01 00:00:00

  • Immature colon carcinoma transcript-1 promotes cell growth of hepatocellular carcinoma via facilitating cell cycle progression and apoptosis resistance.

    abstract::Immature colon carcinoma transcript-1 (ICT1) is a newly identified oncogene, which regulates proliferation, cell cycle progression and apoptosis of cancer cells. However, the clinical significance, biological function and underlying mechanisms of ICT1 in hepatocellular carcinoma (HCC) remain poorly known. In the prese...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2017.6046

    authors: Chang W,Yu Z,Tian M,Lin X

    更新日期:2017-12-01 00:00:00

  • Dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine S-1 may be effective against peritoneal dissemination in gastric cancer.

    abstract::The effects of a novel oral fluoropyrimidine derivative S-1 on peritoneal metastasis from gastric cancer were investigated. OCUM-2MD3 cells, a highly peritoneal-metastatic cell line, were injected intraperitoneally in nude mice. These mice were allocated to the following three groups (each group, n=10): the S-1 group,...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Yamagata S,Nakata B,Hirakawa K

    更新日期:2004-11-01 00:00:00