Decreased miR-340 expression in bone marrow is associated with liver metastasis of colorectal cancer.


:Studies have shown the prognostic significance of disseminated tumor cells (DTC) in bone marrow of patients with colorectal cancer. However, the molecular characteristics of DTCs, including their miRNA expression profiles, remain mostly unknown. In this study, we analyzed the miRNA expression of DTCs in bone marrow. EpCAM(+) bone marrow cells were collected using immunomagnetic beads after exclusion of CD14(+) and CD45(+) cells, then subjected to miRNA microarray analysis. Cluster analysis (7 colorectal cancer patients with liver metastasis and 12 colorectal cancer patients without liver metastasis) indicated that miR-340 and miR-542-3p expressions were significantly decreased in EpCAM(+) bone marrow cells of patients with liver metastasis (P = 0.019 and 0.037, respectively). We demonstrated that pre-miR-340 administration inhibited growth of colon cancer cells and suppressed c-Met expression in vitro. In clinical samples of colorectal cancer, miR-340 was expressed at significantly lower levels in tumor tissues compared with normal mucosa. Survival analysis in 136 patients with colorectal cancer indicated that low miR-340 expression was correlated with shorter 5-year disease-free survival (P = 0.023) and poor 5-year overall survival (P = 0.046). It was of note that the colorectal cancer group with low miR-340 and high c-Met expression had the worst prognosis. We further demonstrated that systemic pre-miR-340 administration suppressed growth of pre-established HCT116 tumors in animal therapeutic models. These findings indicate that miR-340 may be useful as a novel prognostic factor and as a therapeutic tool against colorectal cancer. Our data suggest that miR-340 in bone marrow may play an important role in regulating the metastasis cascade of colorectal cancer.


Mol Cancer Ther


Takeyama H,Yamamoto H,Yamashita S,Wu X,Takahashi H,Nishimura J,Haraguchi N,Miyake Y,Suzuki R,Murata K,Ohue M,Kato T,Takemasa I,Mizushima T,Ishii H,Mimori K,Doki Y,Mori M




Has Abstract


2014-04-01 00:00:00














  • Disruption of SND1-MTDH Interaction by a High Affinity Peptide Results in SND1 Degradation and Cytotoxicity to Breast Cancer Cells In Vitro and In Vivo.

    abstract::Staphylococcal nuclease domain-containing protein 1 (SND1) is a multifunctional oncoprotein overexpressed in breast cancer. Binding of metadherin (MTDH) to SND1 results in the stabilization of SND1 and is important in the initiation and progression of breast cancer. Disruption of such interaction is a potential therap...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Li P,He Y,Chen T,Choy KY,Chow TS,Wong ILK,Yang X,Sun W,Su X,Chan TH,Chow LMC

    更新日期:2021-01-01 00:00:00

  • Recombinant adeno-associated virus encoding Epstein-Barr virus latent membrane proteins fused with heat shock protein as a potential vaccine for nasopharyngeal carcinoma.

    abstract::Nasopharyngeal carcinoma (NPC) is a common cancer in Southern China and EBV is the most important pathogenesis. In this study, we explore the potential that a recombinant adeno-associated virus (rAAV) carrying a fusing gene containing heat shock protein as an adjuvant, EBV latent membrane proteins (LMP1 and LMP2) CTL ...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Pan J,Zhang Q,Zhou J,Ma D,Xiao X,Wang DW

    更新日期:2009-09-01 00:00:00

  • Antitumor efficacy of IPI-504, a selective heat shock protein 90 inhibitor against human epidermal growth factor receptor 2-positive human xenograft models as a single agent and in combination with trastuzumab or lapatinib.

    abstract::IPI-504 is a novel, highly soluble small-molecule inhibitor of heat shock protein 90 (Hsp90), a protein chaperone essential for regulating homeostasis of oncoproteins and cell signaling proteins. Human epidermal growth factor receptor 2 (HER2; ErbB2) oncoprotein, expressed in a subset of metastatic breast cancers, is ...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Leow CC,Chesebrough J,Coffman KT,Fazenbaker CA,Gooya J,Weng D,Coats S,Jackson D,Jallal B,Chang Y

    更新日期:2009-08-01 00:00:00

  • Antimitotic effect of the retinoid 4-oxo-fenretinide through inhibition of tubulin polymerization: a novel mechanism of retinoid growth-inhibitory activity.

    abstract::The retinoid 4-oxo-N-(4-hydroxyphenyl)retinamide (4-oxo-4-HPR), a metabolite of fenretinide (4-HPR) present in plasma of 4-HPR-treated patients, is very effective in inducing growth inhibition and apoptosis in several cancer cell lines. 4-Oxo-4-HPR and 4-HPR have different mechanisms of action because 4-oxo-4-HPR, unl...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Appierto V,Tiberio P,Cavadini E,Casalini P,Cappelletti G,Formelli F

    更新日期:2009-12-01 00:00:00

  • In vitro and in vivo characterization of irreversible mutant-selective EGFR inhibitors that are wild-type sparing.

    abstract::Patients with non-small cell lung carcinoma (NSCLC) with activating mutations in epidermal growth factor receptor (EGFR) initially respond well to the EGFR inhibitors erlotinib and gefitinib. However, all patients relapse because of the emergence of drug-resistant mutations, with T790M mutations accounting for approxi...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Tjin Tham Sjin R,Lee K,Walter AO,Dubrovskiy A,Sheets M,Martin TS,Labenski MT,Zhu Z,Tester R,Karp R,Medikonda A,Chaturvedi P,Ren Y,Haringsma H,Etter J,Raponi M,Simmons AD,Harding TC,Niu D,Nacht M,Westlin WF,Pette

    更新日期:2014-06-01 00:00:00

  • Effects of anti-VEGF on pharmacokinetics, biodistribution, and tumor penetration of trastuzumab in a preclinical breast cancer model.

    abstract::Both human epidermal growth factor receptor 2 (HER-2/neu) and VEGF overexpression correlate with aggressive phenotypes and decreased survival among breast cancer patients. Concordantly, the combination of trastuzumab (anti-HER2) with bevacizumab (anti-VEGF) has shown promising results in preclinical xenograft studies ...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Pastuskovas CV,Mundo EE,Williams SP,Nayak TK,Ho J,Ulufatu S,Clark S,Ross S,Cheng E,Parsons-Reponte K,Cain G,Van Hoy M,Majidy N,Bheddah S,dela Cruz Chuh J,Kozak KR,Lewin-Koh N,Nauka P,Bumbaca D,Sliwkowski M,Tibbitt

    更新日期:2012-03-01 00:00:00

  • Targeting the HER Family with Pan-HER Effectively Overcomes Resistance to Cetuximab.

    abstract::Cetuximab, an antibody against the EGFR, has shown efficacy in treating head and neck squamous cell carcinoma (HNSCC), metastatic colorectal cancer, and non-small cell lung cancer (NSCLC). Despite the clinical success of cetuximab, many patients do not respond to cetuximab. Furthermore, virtually all patients who do i...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Iida M,Bahrar H,Brand TM,Pearson HE,Coan JP,Orbuch RA,Flanigan BG,Swick AD,Prabakaran PJ,Lantto J,Horak ID,Kragh M,Salgia R,Kimple RJ,Wheeler DL

    更新日期:2016-09-01 00:00:00

  • Inhibition of cell growth by NB1011 requires high thymidylate synthase levels and correlates with p53, p21, bax, and GADD45 induction.

    abstract::NB1011, a phosphoramidate derivative of (E)-5-(2-bromovinyl)-2'-deoxyuridine, is a novel small molecule anticancer agent. NB1011 is selectively active against tumor cells expressing high levels of thymidylate synthase (TS), a critical enzyme in DNA biosynthesis. NB1011 is different from the current TS-targeted drugs, ...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Neuteboom ST,Karjian PL,Boyer CR,Beryt M,Pegram M,Wahl GM,Shepard HM

    更新日期:2002-04-01 00:00:00

  • Targeting multiple pathways in gliomas with stem cell and viral delivered S-TRAIL and Temozolomide.

    abstract::Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively kills tumor cells. However, its short half-life, poor delivery, and TRAIL-resistant tumor cells have diminished its clinical efficacy. In this study, we explored whether novel delivery methods will represent new and effective ways to treat gli...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Hingtgen S,Ren X,Terwilliger E,Classon M,Weissleder R,Shah K

    更新日期:2008-11-01 00:00:00

  • Targeting of BRM Sensitizes BRG1-Mutant Lung Cancer Cell Lines to Radiotherapy.

    abstract::Targeting of epigenetic regulators as the chromatin remodeler SWI/SNF is proving to be a promising therapeutic strategy for individualized treatment of cancer patients. Here, we tested whether targeting one of the two mutually exclusive subdomains of the SWI/SNF complex BRM/SMARCA2 can sensitize specifically non-small...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Zernickel E,Sak A,Riaz A,Klein D,Groneberg M,Stuschke M

    更新日期:2019-03-01 00:00:00

  • Restoration of T-cell Effector Function, Depletion of Tregs, and Direct Killing of Tumor Cells: The Multiple Mechanisms of Action of a-TIGIT Antagonist Antibodies.

    abstract::TIGIT is an immune checkpoint inhibitor expressed by effector CD4+ and CD8+ T cells, NK cells, and regulatory T cells (Tregs). Inhibition of TIGIT-ligand binding using antagonistic anti-TIGIT mAbs has shown in vitro potential to restore T-cell function and therapeutic efficacy in murine tumor models when combined with...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Preillon J,Cuende J,Rabolli V,Garnero L,Mercier M,Wald N,Pappalardo A,Denies S,Jamart D,Michaux AC,Pirson R,Pitard V,Bagot M,Prasad S,Houthuys E,Brouwer M,Marillier R,Lambolez F,Marchante JR,Nyawouame F,Carter MJ

    更新日期:2021-01-01 00:00:00

  • Hsp90 inhibitors promote p53-dependent apoptosis through PUMA and Bax.

    abstract::Hsp90 is widely overexpressed in cancer cells and believed to be essential for the maintenance of malignant phenotypes. Targeting Hsp90 by small molecules has shown promise in solid and hematologic malignancies, which likely involves degradation of client oncoproteins in a cell-type-specific manner. In this study, we ...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: He K,Zheng X,Zhang L,Yu J

    更新日期:2013-11-01 00:00:00

  • In Vitro and In Vivo Synergistic Antitumor Activity of the Combination of BKM120 and Erlotinib in Head and Neck Cancer: Mechanism of Apoptosis and Resistance.

    abstract::We previously reported that the EGFR-targeted inhibitor erlotinib induces G1 arrest of squamous cell carcinoma of the head and neck (SCCHN) cell lines without inducing significant apoptosis. Large-scale genomic studies suggest that >50% of SCCHN cases have activation of PI3K pathways. This study investigated whether c...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Anisuzzaman AS,Haque A,Wang D,Rahman MA,Zhang C,Chen Z,Chen ZG,Shin DM,Amin AR

    更新日期:2017-04-01 00:00:00

  • Enhanced Antitumor Efficacy of Oncolytic Adenovirus-loaded Menstrual Blood-derived Mesenchymal Stem Cells in Combination with Peripheral Blood Mononuclear Cells.

    abstract::Several studies have evaluated the efficacy of using human oncolytic adenovirus (OAdv)-loaded mesenchymal stem cells (MSC) for cancer treatment. For example, we have described the antitumor efficacy of CELYVIR, autologous bone marrow-mesenchymal stem cells infected with the OAdv ICOVIR-5, for treatment of patients wit...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Moreno R,Fajardo CA,Farrera-Sal M,Perisé-Barrios AJ,Morales-Molina A,Al-Zaher AA,García-Castro J,Alemany R

    更新日期:2019-01-01 00:00:00

  • ANG4043, a novel brain-penetrant peptide-mAb conjugate, is efficacious against HER2-positive intracranial tumors in mice.

    abstract::Anti-HER2 monoclonal antibodies (mAb) have been shown to reduce tumor size and increase survival in patients with breast cancer, but they are ineffective against brain metastases due to poor brain penetration. In previous studies, we identified a peptide, known as Angiopep-2 (An2), which crosses the blood-brain barrie...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Regina A,Demeule M,Tripathy S,Lord-Dufour S,Currie JC,Iddir M,Annabi B,Castaigne JP,Lachowicz JE

    更新日期:2015-01-01 00:00:00

  • Resolving conflicting data on expression of the Tn antigen and implications for clinical trials with cancer vaccines.

    abstract::The tumor-associated Tn antigen has been investigated extensively as a biomarker and therapeutic target. Cancer vaccines containing the Tn antigen as a single tumor antigen or as a component of a polyvalent vaccine have progressed into phase I and II clinical trials. One major focus of Tn-based vaccines is the treatme...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Li Q,Anver MR,Butcher DO,Gildersleeve JC

    更新日期:2009-04-01 00:00:00

  • Antitumor mechanisms of combined gastrin-releasing peptide receptor and epidermal growth factor receptor targeting in head and neck cancer.

    abstract::Head and neck squamous cell carcinoma (HNSCC) is characterized by epidermal growth factor receptor (EGFR) overexpression, where EGFR levels correlate with survival. To date, EGFR targeting has shown limited antitumor effects in head and neck cancer when administrated as monotherapy. We previously identified a gastrin-...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Zhang Q,Bhola NE,Lui VW,Siwak DR,Thomas SM,Gubish CT,Siegfried JM,Mills GB,Shin D,Grandis JR

    更新日期:2007-04-01 00:00:00

  • Eps8 decreases chemosensitivity and affects survival of cervical cancer patients.

    abstract::The oncoprotein Eps8 facilitates proliferation in fibroblasts and colon cancer cells. However, its role in human cervical cancer is unclear. By immunohistochemical staining and Western blotting, aberrant Eps8 expression was observed in cervical carcinoma compared with normal cervical epithelial cells. Clinicopathologi...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Chen YJ,Shen MR,Chen YJ,Maa MC,Leu TH

    更新日期:2008-06-01 00:00:00

  • TTK Inhibitors as a Targeted Therapy for CTNNB1 (β-catenin) Mutant Cancers.

    abstract::The spindle assembly checkpoint kinase TTK (Mps1) is a key regulator of chromosome segregation and is the subject of novel targeted therapy approaches by small-molecule inhibitors. Although the first TTK inhibitors have entered phase I dose escalating studies in combination with taxane chemotherapy, a patient stratifi...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Zaman GJR,de Roos JADM,Libouban MAA,Prinsen MBW,de Man J,Buijsman RC,Uitdehaag JCM

    更新日期:2017-11-01 00:00:00

  • EpCAM-targeted delivery of nanocomplexed siRNA to tumor cells with designed ankyrin repeat proteins.

    abstract::Specific delivery to tumors and efficient cellular uptake of nucleic acids remain major challenges for gene-targeted cancer therapies. Here we report the use of a designed ankyrin repeat protein (DARPin) specific for the epithelial cell adhesion molecule (EpCAM) as a carrier for small interfering RNA (siRNA) complemen...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Winkler J,Martin-Killias P,Plückthun A,Zangemeister-Wittke U

    更新日期:2009-09-01 00:00:00

  • EGF Receptor and mTORC1 Are Novel Therapeutic Targets in Nonseminomatous Germ Cell Tumors.

    abstract::Germ cell tumors (GCT) are malignant tumors that arise from pluripotent embryonic germ cells and occur in children and young adults. GCTs are treated with cisplatin-based regimens which, while overall effective, fail to cure all patients and cause significant adverse late effects. The seminoma and nonseminoma forms of...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Chen KS,Fustino NJ,Shukla AA,Stroup EK,Budhipramono A,Ateek C,Stuart SH,Yamaguchi K,Kapur P,Frazier AL,Lum L,Looijenga LHJ,Laetsch TW,Rakheja D,Amatruda JF

    更新日期:2018-05-01 00:00:00

  • Camptothecin poly[n-(2-hydroxypropyl) methacrylamide] copolymers in antitopoisomerase-I tumor therapy: intratumor release and antitumor efficacy.

    abstract::Soluble copolymers of camptothecin (CPT), based on poly[N-(2-hydroxypropyl) methacrylamide] (pHPMA), were obtained by conjugation through the degradable spacers -Gly-Phe-Leu-Gly- or -Gly-6-aminohexanoyl-Gly-. We investigated to what extent passive accumulation and retention of hydroxypropyl methacrylamide copolymer of...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Zamai M,VandeVen M,Farao M,Gratton E,Ghiglieri A,Castelli MG,Fontana E,D'Argy R,Fiorino A,Pesenti E,Suarato A,Caiolfa VR

    更新日期:2003-01-01 00:00:00

  • The TLR3 Agonist Inhibit Drug Efflux and Sequentially Consolidates Low-Dose Cisplatin-Based Chemoimmunotherapy while Reducing Side Effects.

    abstract::The traditional maximum dose density chemotherapy renders the tumor patients not only the tumor remission but the chemotherapy resistance and more adverse side effects. According to the widely positive expression of Toll-like receptor (TLR)-3 in oral squamous cell carcinoma (OSCC) patients (n = 166), we here provided ...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Ding L,Ren J,Zhang D,Li Y,Huang X,Ji J,Hu Q,Wang H,Ni Y,Hou Y

    更新日期:2017-06-01 00:00:00

  • HER2 as therapeutic target for overcoming ATP-binding cassette transporter-mediated chemoresistance in small cell lung cancer.

    abstract::Small cell lung cancer (SCLC) easily acquires multidrug resistance after successful initial therapy. Overexpression of ATP-binding cassette (ABC) transporters is important for the multidrug resistance. Among them, ABCB1 and ABCG2 are known to be upregulated in chemoresistant SCLC cells. We found that human epidermal g...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Minami T,Kijima T,Otani Y,Kohmo S,Takahashi R,Nagatomo I,Hirata H,Suzuki M,Inoue K,Takeda Y,Kida H,Tachibana I,Kumanogoh A

    更新日期:2012-04-01 00:00:00

  • Dual Inhibition of Key Proliferation Signaling Pathways in Triple-Negative Breast Cancer Cells by a Novel Derivative of Taiwanin A.

    abstract::The treatment of breast cancer cells obtained by blocking the aberrant activation of the proliferation signaling pathways PI3K/Akt/mTOR and MEK/ERK has received considerable attention in recent years. Previous studies showed that Taiwanin A inhibited the proliferation of several types of cancer cells. In this study, w...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Kuo YH,Chiang EI,Chao CY,Rodriguez RL,Chou PY,Tsai SY,Pai MH,Tang FY

    更新日期:2017-03-01 00:00:00

  • Activity of PXD101, a histone deacetylase inhibitor, in preclinical ovarian cancer studies.

    abstract::Histone deacetylase inhibitors represent a promising new class of anticancer agents. In the current investigation, we examined the activity of PXD101, a potent histone deacetylase inhibitor, used alone or in combination with clinically relevant chemotherapeutics (docetaxel, paclitaxel, and carboplatin), in preclinical...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Qian X,LaRochelle WJ,Ara G,Wu F,Petersen KD,Thougaard A,Sehested M,Lichenstein HS,Jeffers M

    更新日期:2006-08-01 00:00:00

  • Efficacy of the MDM2 Inhibitor SAR405838 in Glioblastoma Is Limited by Poor Distribution Across the Blood-Brain Barrier.

    abstract::Controversy exists surrounding whether heterogeneous disruption of the blood-brain barrier (BBB), as seen in glioblastoma (GBM), leads to adequate drug delivery sufficient for efficacy in GBM. This question is especially important when using potent, targeted agents that have a poor penetration across an intact BBB. Ef...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Kim M,Ma DJ,Calligaris D,Zhang S,Feathers RW,Vaubel RA,Meaux I,Mladek AC,Parrish KE,Jin F,Barriere C,Debussche L,Watters J,Tian S,Decker PA,Eckel-Passow JE,Kitange GJ,Johnson AJ,Parney IF,Anastasiadis PZ,Agar NYR

    更新日期:2018-09-01 00:00:00

  • Transduction of green fluorescent protein increased oxidative stress and enhanced sensitivity to cytotoxic drugs in neuroblastoma cell lines.

    abstract::Green fluorescent protein (GFP) is employed as a selection marker for gene transduction and to track tumor cells. Transduction of enhanced GFP (eGFP) into human neuroblastoma cell lines via a lentiviral vector significantly sensitized CHLA-20 (wild-type and functional TP53), and to a lesser extent CHLA-90 cells (multi...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Goto H,Yang B,Petersen D,Pepper KA,Alfaro PA,Kohn DB,Reynolds CP

    更新日期:2003-09-01 00:00:00

  • Combined targeting of epidermal growth factor receptor and hedgehog signaling by gefitinib and cyclopamine cooperatively improves the cytotoxic effects of docetaxel on metastatic prostate cancer cells.

    abstract::The epidermal growth factor receptor (EGFR) and hedgehog cascades provide a critical role in prostate cancer progression and contribute to the resistance to clinical therapies and disease relapse. Therefore, we evaluated, for the first time, the antiproliferative and cytotoxic effects induced by a combination of selec...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Mimeault M,Johansson SL,Vankatraman G,Moore E,Henichart JP,Depreux P,Lin MF,Batra SK

    更新日期:2007-03-01 00:00:00

  • The insulin-like growth factor-I (IGF-I) receptor kinase inhibitor NVP-ADW742, in combination with STI571, delineates a spectrum of dependence of small cell lung cancer on IGF-I and stem cell factor signaling.

    abstract::Stem cell factor (SCF)/Kit and insulin-like growth factor-I (IGF-I)/IGF-I receptor (IGF-IR) autocrine loops play a prominent role in the growth of small cell lung cancer (SCLC). Previous data suggested that IGF-I protects cells from apoptosis induced by STI571, an efficient inhibitor of Kit signal transduction, by act...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Warshamana-Greene GS,Litz J,Buchdunger E,Hofmann F,García-Echeverría C,Krystal GW

    更新日期:2004-05-01 00:00:00