MiR-181a, a new regulator of TGF-β signaling, can promote cell migration and proliferation in gastric cancer.

Abstract:

:Transforming growth factor-beta (TGF-β) signaling pathway plays pivotal roles in various types of cancer. TGF-β receptor 2 (TGFβR2) contains a kinase domain that phosphorylates and activates the downstream of the TGF-β signaling pathway. Our previous microarray analysis revealed marked changes in miR-181a expression in gastric cancers, and the bioinformatics analysis suggested that miR-181a negatively regulated TGFβR2. In order to verify the effect of miR-181a on TGFβR2 and clarify the influence of miR-181a on the migration and proliferation of gastric cancer, studies in gastric cancer cell lines and xenograft mouse models were carried out. We found that a reduced expression of TGFβR2 and an increased expression miR-181a in gastric cancer tissues compared to adjacent noncancerous tissues. A luciferase reporter assay confirmed that TGFβR2 was a target of miR-181a. In addition, we found that miR-181a mimics, which increased the level of miR-181a, downregulated the expression of TGFβR2 in the gastric cancer cell line SGC-7901. Moreover, both the overexpression of miR-181a and the downregulation of TGFβR2 promoted the migration and proliferation of SGC-7901 cells. Conversely, SGC-7901 cell migration and proliferation were inhibited by the downregulation of miR-181a and the overexpression of TGFβR2. Furthermore, the increased expression of miR-181a and the decreased expression of TGFβR2 also enhanced the tumor growth in mice bearing gastric cancer. Our results herein indicated that miR-181a promoted the migration and proliferation of gastric cancer cells by downregulating TGFβR2 at the posttranscriptional level. The present study suggests that miR-181a is a novel negative regulator of TGFβR2 in the TGF-β signaling pathway and thus represents a potential new therapeutic target for gastric cancer.

journal_name

Invest New Drugs

authors

Ge S,Zhang H,Deng T,Sun W,Ning T,Fan Q,Wang Y,Wang X,Zhang Q,Zhou Z,Yang H,Ying G,Ba Y

doi

10.1007/s10637-018-0695-5

subject

Has Abstract

pub_date

2019-10-01 00:00:00

pages

923-934

issue

5

eissn

0167-6997

issn

1573-0646

pii

10.1007/s10637-018-0695-5

journal_volume

37

pub_type

杂志文章
  • Targeting histone deacetyalses in the treatment of B- and T-cell malignancies.

    abstract::HDAC inhibitors (HDACI) are now emerging as one of the most promising new classes of drugs for the treatment of select forms of non-Hodgkin's lymphoma (NHL). They are particularly active in T-cell lymphomas, possibly hodgkin's lymphoma and indolent B cell lymphomas. Presently, two of these agents, vorinostat and romid...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-010-9591-3

    authors: Zain J,O'Connor OA

    更新日期:2010-12-01 00:00:00

  • Mitoxantrone in the treatment of relapsed and refractory acute leukemia.

    abstract::Twenty-four patients with acute leukemia or blast crisis (BC) of chronic myelocytic leukemia (CML) in relapse or refractory to standard chemotherapy, were eligible for treatment with mitoxantrone. Mitoxantrone (Novantrone; dihydroxyanthracenedione) was administered in a dose of 8-13 mg/m2 on five consecutive days. Fiv...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/BF00174171

    authors: Meyer P,Ho AD,Ehninger G,Mjaaland I,Heidemann E,Seither E

    更新日期:1985-01-01 00:00:00

  • Nafazatrom: clonogenic in-vitro assessment of activity against human malignancies.

    abstract::Nafazatrom was tested against a variety of human malignancies with the human tumor stem cell assay at one or more of the following concentrations: 1, 10, 25, and 100 micrograms/ml X 1 h or 0.05, 0.5, or 5 micrograms/ml by continuous exposure. Major (greater than or equal to 70%) inhibition was noted in 7/52 adenocarci...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/BF00173781

    authors: Haas CD,Kyle GW,Crissman JD,Schaldenbrand MF

    更新日期:1984-01-01 00:00:00

  • Continuing pursuit for ideal systemic anticancer radiotherapeutics.

    abstract::Cancer is one of the major causes of death for non-transmissible chronic diseases worldwide. Conventional treatments including surgery, chemotherapy and external beam radiotherapy are generally far from curative. Complementary therapies are attempted for achieving more successful treatment response. Systemic targeted ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,评审

    doi:10.1007/s10637-011-9758-6

    authors: Cona MM,Wang H,Li J,Feng Y,Chen F,de Witte P,Verbruggen A,Ni Y

    更新日期:2012-10-01 00:00:00

  • A phase I and pharmacokinetic study of trimetrexate using a 24-hour continuous-injection schedule.

    abstract::Trimetrexate (TMTX) is an analog of methotrexate and a potent inhibitor of the enzyme dihydrofolate reductase. In this phase I study, TMTX was given intravenously to 32 patients as a constant infusion over 24 hours every 28 days. The maximum-tolerated dose of TMTX was 200 mg/m2, with myelosuppression as the dose-limit...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/BF00177251

    authors: Allegra CJ,Jenkins J,Weiss RB,Balis F,Drake JC,Brooks J,Thomas R,Curt GA

    更新日期:1990-05-01 00:00:00

  • Silibinin ameliorates oxidative stress induced aberrant crypt foci and lipid peroxidation in 1, 2 dimethylhydrazine induced rat colon cancer.

    abstract::Pharmacological intervention to reduce CRC mortality entails the use of oral agents that can avert carcinogenesis. Silibinin, a major component of silymarin isolated from Silybum marianum (L.) was found to possess attractive remedial features. An in vivo study was designed to elucidate the effect of silibinin on the f...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-009-9237-5

    authors: Sangeetha N,Aranganathan S,Nalini N

    更新日期:2010-06-01 00:00:00

  • Phase II trial of topotecan in advanced gastric cancer: a Southwest Oncology Group study.

    abstract::Topotecan (NSC 609099) is a camptothecin analogue that demonstrated activity against a variety of human tumors in preclinical studies. A phase II trial was performed with topotecan given to patients with locally advanced or metastatic adenocarcinoma of the stomach. Topotecan was administered IV Bolus over 30 minutes o...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章

    doi:10.1023/a:1005899720463

    authors: Benedetti JK,Burris HA 3rd,Balcerzak SP,Macdonald JS

    更新日期:1997-01-01 00:00:00

  • Phase II study of flutamide as second line chemotherapy in patients with advanced pancreatic cancer.

    abstract::Androgen receptors are present in both pancreatic cancer tissue and cell lines. Flutamide is a potent antiandrogen widely used in clinical practice for patients with metastatic prostate cancer. This Phase II trial was undertaken to evaluate the impact of flutamide in patients with advanced pancreatic adenocarcinoma wh...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章

    doi:10.1023/a:1005989519350

    authors: Sharma JJ,Razvillas B,Stephens CD,Hilsenbeck SG,Sharma A,Rothenberg ML

    更新日期:1997-01-01 00:00:00

  • A phase II trial of ganetespib, a heat shock protein 90 Hsp90) inhibitor, in patients with docetaxel-pretreated metastatic castrate-resistant prostate cancer (CRPC)-a prostate cancer clinical trials consortium (PCCTC) study.

    abstract:INTRODUCTION:Heat shock protein 90 (Hsp90) has been studied as a therapeutic target in many cancers. In preclinical trials, the Hsp90 ATPase inhibitor ganetespib demonstrated potent inhibition of solid tumor growth, with superior potency than prior Hsp90 inhibitors. Given the promising preclinical outcome and favorable...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s10637-015-0307-6

    authors: Thakur MK,Heilbrun LK,Sheng S,Stein M,Liu G,Antonarakis ES,Vaishampayan U,Dzinic SH,Li X,Freeman S,Smith D,Heath EI

    更新日期:2016-02-01 00:00:00

  • Cytotoxic flavonoids and isoflavonoids from Erythrina sigmoidea towards multi-factorial drug resistant cancer cells.

    abstract:INTRODUCTION:Continuous efforts from scientists of diverse fields are necessary not only to better understand the mechanism by which multidrug resistant (MDR) cancer cells occur, but also to boost the discovery of new cytotoxic compounds. This work was designed to assess the cytotoxicity and the mechanism of action of ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-014-0137-y

    authors: Kuete V,Sandjo LP,Djeussi DE,Zeino M,Kwamou GM,Ngadjui B,Efferth T

    更新日期:2014-12-01 00:00:00

  • Effects of the tumor vasculature targeting agent NGR-TNF on the tumor microenvironment in murine lymphomas.

    abstract::TNF-alpha may improve drug delivery to tumors by alteration of vascular permeability. However, toxicity precludes its systemic administration in patients. NGR-TNF comprises TNF coupled to the peptide CNGRC, which is a ligand for CD13. CD13 is expressed on tumor vasculature. Therefore, to assess the efficacy of NGR-TNF...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-005-4540-2

    authors: van Laarhoven HW,Gambarota G,Heerschap A,Lok J,Verhagen I,Corti A,Toma S,Gallo Stampino C,van der Kogel A,Punt CJ

    更新日期:2006-01-01 00:00:00

  • Phase II study of gemcitabine for treatment of patients with advanced stage marginal zone B-cell lymphoma: Consortium for Improving Survival of Lymphoma (CISL) trial.

    abstract:BACKGROUND:Therapeutic approaches to marginal zone B-cell lymphoma (MZL) continue to evolve. Localized MZL responds favorably to local treatments, including surgery and/or local radiation therapy. However, MZL manifests as a disseminated disease in one-third of the cases at diagnosis. Moreover, relapses involving dista...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s10637-009-9260-6

    authors: Oh SY,Kim WS,Lee DH,Kim SJ,Kim SH,Ryoo BY,Kang HJ,Choi YJ,Chung JS,Kim HJ,Suh C

    更新日期:2010-04-01 00:00:00

  • Cytotoxicity of withaferin A in glioblastomas involves induction of an oxidative stress-mediated heat shock response while altering Akt/mTOR and MAPK signaling pathways.

    abstract::Withaferin A (WA), a steroidal lactone derived from the plant Vassobia breviflora, has been reported to have anti-proliferative, pro-apoptotic, and anti-angiogenic properties against cancer growth. In this study, we identified several key underlying mechanisms of anticancer action of WA in glioblastoma cells. WA was f...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-012-9888-5

    authors: Grogan PT,Sleder KD,Samadi AK,Zhang H,Timmermann BN,Cohen MS

    更新日期:2013-06-01 00:00:00

  • Phase I trial of 4-demethoxydaunorubicin (idarubicin) with single oral doses.

    abstract::Twenty-four patients with a variety of solid tumors entered a Phase I trial with 4-demethoxydaunorubicin, a new analogue of daunorubicin. The drug was given as a single oral dose of 10-60 mg/m2 repeated every 3-4 weeks. Leukopenia was the dose-limiting toxicity. Other toxic effects included mild to moderate nausea and...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/BF00175378

    authors: Kaplan S,Sessa C,Willems Y,Pacciarini MA,Tamassia V,Cavalli F

    更新日期:1984-01-01 00:00:00

  • Eugenol inhibits cell proliferation via NF-κB suppression in a rat model of gastric carcinogenesis induced by MNNG.

    abstract::The modulation of intracellular nuclear factor-kappaB (NF-κB) signaling pathway involved in the deregulated expression of cell proliferation and cell cycle regulatory molecules is a pragmatic approach for chemoprevention. Eugenol (4-allyl-1-hydroxy-2-methoxybenzene), a natural phenolic constituent of oils of cloves is...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-009-9345-2

    authors: Manikandan P,Vinothini G,Vidya Priyadarsini R,Prathiba D,Nagini S

    更新日期:2011-02-01 00:00:00

  • A study of a different dose-intense infusion schedule of phenylacetate in patients with recurrent primary brain tumors consortium report.

    abstract:PURPOSE:To compare two different infusion schedules of phenylacetate (PA) in patients with primary brain tumors and to assess the feasibility of the administration in a multi-institutional setting. PATIENTS AND METHODS:Adult patients with recurrent primary brain tumors were treated with PA on two different schedules. ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1023/a:1026299118067

    authors: Chang SM,Kuhn JG,Ian Robins H,Clifford Schold S,Spence AM,Berger MS,Mehta MP,Pollack I,Gilbert M,Prados MD

    更新日期:2003-11-01 00:00:00

  • Multifunctional 5-aminolevulinic acid prodrugs activating diverse cell-death pathways.

    abstract::Herein we describe a series of multifunctional 5-aminolevulinic-acid (ALA) prodrugs for photodynamic dependent and independent cancer therapy (PDT). We studied the cell-death mechanisms in glioblastoma U251 cells treated with four ALA-prodrugs: (1) AlaAcBu, that releases ALA, acetaldehyde, and butyric acid; (2) AlaFaB...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-011-9669-6

    authors: Berkovitch-Luria G,Weitman M,Nudelman A,Rephaeli A,Malik Z

    更新日期:2012-06-01 00:00:00

  • Differences in drug approval processes of 3 regulatory agencies: a case study of gemtuzumab ozogamicin.

    abstract::Major discrepancies concerning risk-benefit assessments and regulatory actions are frequent among regulatory agencies. We explored the differences by scrutinizing a case of gemtuzumab ozogamicin (GO) in patients with acute myeloid leukaemia (AML). Assessment reports of GO were retrieved form the websites of the US Foo...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,评审

    doi:10.1007/s10637-012-9877-8

    authors: Tanimoto T,Tsubokura M,Mori J,Pietrek M,Ono S,Kami M

    更新日期:2013-04-01 00:00:00

  • A retrospective pooled analysis of trabectedin safety in 1,132 patients with solid tumors treated in phase II clinical trials.

    abstract:PURPOSE:To summarize the safety experience obtained from phase II clinical trials conducted with trabectedin as single-agent therapy in patients with advanced solid tumors. METHODS:This retrospective analysis includes 1,132 patients exposed to trabectedin in 19 phase II trials carried out between February 1999 and Apr...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-011-9662-0

    authors: Le Cesne A,Yovine A,Blay JY,Delaloge S,Maki RG,Misset JL,Frontelo P,Nieto A,Jiao JJ,Demetri GD

    更新日期:2012-06-01 00:00:00

  • The flavonoid luteolin suppresses infantile hemangioma by targeting FZD6 in the Wnt pathway.

    abstract::Infantile hemangioma is the most common vascular tumor of childhood. It is characterized by clinical expansion of endothelial cells and promoted by angiogenic factors. Luteolin is a flavonoid compound that carries anti-cancer and anti-angiogenesis properties. The study aimed to investigate the effect of luteolin in tr...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-020-01052-8

    authors: Dai Y,Zheng H,Liu Z,Wang Y,Hu W

    更新日期:2021-01-07 00:00:00

  • Circulating vascular endothelial growth factor receptor 2/pAkt-positive cells as a functional pharmacodynamic marker in metastatic colorectal cancers treated with antiangiogenic agent.

    abstract:OBJECTIVE:The anti-vascular endothelial growth factor (VEGF) antibody bevacizumab has received considerable attention as a first-line treatment of advanced colorectal cancers. Difficulties associated with effectively monitoring the activity of this drug have prompted us to seek a pharmacodynamic marker suitable for def...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-012-9817-7

    authors: Shin SJ,Hwang JW,Ahn JB,Rha SY,Roh JK,Chung HC

    更新日期:2013-02-01 00:00:00

  • A phase II study of bosentan, a dual endothelin receptor antagonist, as monotherapy in patients with stage IV metastatic melanoma.

    abstract::There is no effective systemic therapy for disseminated metastatic melanoma. Data suggest that endothelin may play a role in pathophysiology of melanoma and that the dual endothelin receptor antagonist bosentan may have anti-tumor activity. This multicenter, open-label, single-arm, prospective, proof-of-concept study ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s10637-006-9014-7

    authors: Kefford R,Beith JM,Van Hazel GA,Millward M,Trotter JM,Wyld DK,Kusic R,Shreeniwas R,Morganti A,Ballmer A,Segal E,Nayler O,Clozel M

    更新日期:2007-06-01 00:00:00

  • Predictive factors for response to treatment in patients with advanced renal cell carcinoma.

    abstract:INTRODUCTION:The analysis of predictive factors of response may aid in predicting which patients with advanced renal cell carcinoma (RCC) would be good candidates for systemic treatments. MATERIALS AND METHODS:The expression of several biomarkers was retrospectively analyzed using immunohistochemistry (IHC), as well a...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-012-9836-4

    authors: Muriel López C,Esteban E,Astudillo A,Pardo P,Berros JP,Izquierdo M,Crespo G,Fonseca PJ,Sanmamed M,Martínez-Camblor P

    更新日期:2012-12-01 00:00:00

  • Stathmin 1 is highly expressed and associated with survival outcome in malignant adrenocortical tumours.

    abstract::Adrenocortical carcinoma (ACC) is an aggressive endocrine cancer with few molecular predictors of malignancy and survival, especially in paediatric patients. Stathmin 1 (STMN1) regulates microtubule dynamics and has been involved in the malignant phenotype of cancer cells. Recently, it was reported that STMN1 is highl...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-019-00846-9

    authors: Dos Santos Passaia B,Lima K,Kremer JL,da Conceição BB,de Paula Mariani BM,da Silva JCL,Zerbini MCN,Fragoso MCBV,Machado-Neto JA,Lotfi CFP

    更新日期:2020-06-01 00:00:00

  • Using the neurotransmitter serotonin to target imaging agents to glioblastoma cells.

    abstract::The neurotransmitter serotonin is involved in numerous bodily functions via seven different serotonin receptor subfamilies. Serotonin plays a role in gastrointestinal functions like intestinal secretion or peristalsis and neuropsychiatric events like depression or migraine. One of these subtypes has been found on glio...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-011-9781-7

    authors: Sturzu A,Sheikh S,Klose U,Echner H,Kalbacher H,Deeg M,Nägele T,Horger M,Ernemann U,Heckl S

    更新日期:2012-12-01 00:00:00

  • Topophore C: a liposomal nanoparticle formulation of topotecan for treatment of ovarian cancer.

    abstract::We have recently developed a liposomal nanoparticle (LNP) formulation of irinotecan based on loading method that involves formation of a complex between copper and the water soluble camptothecin. The loading methodology developed for irinotecan was evaluated to develop a LNP topotecan formulation (referred to herein a...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-012-9832-8

    authors: Patankar NA,Waterhouse D,Strutt D,Anantha M,Bally MB

    更新日期:2013-02-01 00:00:00

  • Pharmacokinetic interaction involving sorafenib and the calcium-channel blocker felodipine in a patient with hepatocellular carcinoma.

    abstract::Sorafenib, an orally active multi-kinase inhibitor approved for the treatment of hepatocellular carcinoma (HCC), is primarily metabolized both via cytochrome P450 3A4 isoform (CYP3A4) and UGT1A9. Due to the contribution of these two biotransformation pathways, sorafenib is considered to be less susceptible than other ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-010-9514-3

    authors: Gomo C,Coriat R,Faivre L,Mir O,Ropert S,Billemont B,Dauphin A,Tod M,Goldwasser F,Blanchet B

    更新日期:2011-12-01 00:00:00

  • Schedule-dependent inhibition of T-cell lymphoma cells by cotreatment with the mTOR inhibitor everolimus and anticancer drugs.

    abstract:OBJECTIVE:Everolimus (RAD001) is a novel mammalian target of rapamycin (mTOR) inhibitor, and anti-proliferative activity in various malignancies has been reported. This study evaluated the anti-tumor effects and schedule-dependent synergism of everolimus in combination with other chemotherapeutic agents in T-cell lymph...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-010-9558-4

    authors: Huang JJ,Li ZM,Huang Y,Huang Y,Tian Y,He XX,Xiao J,Lin TY

    更新日期:2012-02-01 00:00:00

  • Phase I trial of a novel matrix metalloproteinase inhibitor batimastat (BB-94) in patients with advanced cancer.

    abstract::Degradation of basement membrane and extracellular matrix by matrix metalloproteinases (MMPs) is believed to be required for tumor invasion, tumor-induced angiogenesis and vascular invasion. A synthetic hydroxamate, batimastat (also known as BB-94), inhibits MMPs by binding the zinc ion in the active site of the MMP. ...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章

    doi:10.1007/BF00210790

    authors: Wojtowicz-Praga S,Low J,Marshall J,Ness E,Dickson R,Barter J,Sale M,McCann P,Moore J,Cole A,Hawkins MJ

    更新日期:1996-01-01 00:00:00

  • Phase II trial of 4' deoxydoxorubicin (DXDX) for unresectable non-small cell bronchogenic carcinoma. An Illinois Cancer Council study.

    abstract::A phase II trial of 4' Deoxydoxorubicin (DXDX) was conducted in unresectable previously untreated non-small cell lung cancer patients. DXDX was administered every 3 weeks by short intravenous infusion at a starting dose of 30 mg/m2, with dose escalation to 40 mg/m2 toxicity permitting. Four responses, all partial, wer...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1007/BF00216932

    authors: Rose C,Lad TE,Kilton LJ,Schor J,Rosen ST,Rossof AH,Blough RR,Johnson CM

    更新日期:1990-02-01 00:00:00