978: Introduction of Midkine Gene Into Human Bladder Cancer Cells Enhances their Malignant Phenotype but Inceases in Sensitivity to Antiangiogenic Agent, TNP-470

Muramaki, Mototsugu; Hara, Isao; Kawabata, Gaku; Kamidono, Sadao

doi:10.1016/s0022-5347(18)38215-6

Cited by 20 publications

(27 citation statements)

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“…Expression of HAI-1 is inversely related to invasion and metastasis (Parr and Jiang, 2001), and low expression is considered to be an indicator of poor prognosis in some cancers (Nakamura et al , 2009). Midkine is an angiogenic growth factor normally expressed in the foetus but also re-expressed in many types of cancer (Muramaki et al , 2003). Midkine mRNA has been reported to be upregulated in UCB tissue and associated with late-stage disease and poor prognosis (O'Brien et al , 1996).…”

Section: Discussionmentioning

confidence: 99%

Combined proteome and transcriptome analyses for the discovery of urinary biomarkers for urothelial carcinoma

et al. 2013

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Background:Proteomic discovery of cancer biomarkers in body fluids is challenging because of their low abundance in a complex background. Altered gene expression in tumours may not reflect protein levels in body fluids. We have tested combining gene expression profiling of tumours with proteomic analysis of cancer cell line secretomes as a strategy to discover urinary biomarkers for bladder cancer.Methods:We used shotgun proteomics to identify proteins secreted by three bladder cancer cell lines. Secreted proteins with high mRNA levels in bladder tumours relative to normal urothelium were assayed by ELISA in urine samples from 642 patients.Results:Midkine and HAI-1 were significantly increased in bladder cancer patients, with the highest levels in invasive disease (area under the receiver operating characteristic curve 0.89 vs non-cancer). The urinary concentration of both proteins was too high to be explained by bladder cancer associated haematuria and most likely arises by direct tumour secretion.Conclusions:This ‘dual-omic' strategy identified tumour secreted proteins whose urine concentrations are increased significantly by bladder cancer. Combined secretome-transcriptome analysis may be more useful than direct proteomic analysis of body fluids for biomarker discovery in both bladder cancer and other tumour types.

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Section: Discussionmentioning

confidence: 99%

Combined proteome and transcriptome analyses for the discovery of urinary biomarkers for urothelial carcinoma

et al. 2013

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“…The in vitro washout and internalization studies showed the UM-UC-3R cells internalize the belinostat NPs and preserve a histone hyperace-tylation state for a longer duration than unencapsulated drug. 39–41 Using NPs, we provided an in vivo dose of belinostat that was ~100 times the IC 50 for bladder cancer cells. When functionalized with PGON, belinostat-loaded NPs that were injected into the tumors reduced tumor growth for at least 11 days, while tumor volume of control and NP-Bk-PGON injected tumors doubled.…”

Section: Discussionmentioning

confidence: 99%

Nanoparticles for urothelium penetration and delivery of the histone deacetylase inhibitor belinostat for treatment of bladder cancer

Martín

Hoimes

Kaimakliotis

et al. 2013

Nanomedicine: Nanotechnology, Biology and Medicine

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Nearly 40% of patients with non-invasive bladder cancer will progress to invasive disease despite locally-directed therapy. Overcoming the bladder permeability barrier (BPB) is a challenge for intravesical drug delivery. Using the fluorophore coumarin (C6), we synthesized C6-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs), which were surface modified with a novel cell penetrating polymer, poly(guanidinium oxanorbornene) (PGON). Addition of PGON to the NP surface improved tissue penetration by 10-fold in intravesically-treated mouse bladder and ex vivo human ureter. In addition, NP-C6-PGON significantly enhanced intracellular uptake of NPs compared to NPs without PGON. To examine biological activity, we synthesized NPs that were loaded with the histone deacetylase (HDAC) inhibitor belinostat (NP-Bel-PGON). NP-Bel-PGON exhibited a significantly lower IC50 in cultured bladder cancer cells, and sustained hyperacetylation, when compared to unencapsulated belinostat. Xenograft tumors treated with NP-Bel-PGON showed a 70% reduction in volume, and a 2.5-fold higher intratumoral acetyl-H4, when compared to tumors treated with unloaded NP-PGON.

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“…It can act as an angiogenic, fibrinolytic and antiapoptotic factor in carcinoma cell lines, and induce the transformation of NIH/3T3, SW-13 and UN-UC-3 cells [1,2]. MK is also detected in some normal human tissues.…”

Section: Introductionmentioning

confidence: 99%

siRNA targeting midkine inhibits gastric cancer cells growth and induces apoptosis involved caspase-3,8,9 activation and mitochondrial depolarization

Wang

Huang

et al. 2007

J Biomed Sci

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Midkine (MK), a heparin-binding growth factor, is expressed highly in various malignant tumors, so it acts as attractive therapeutic target. In the present study, we used siRNA targeting MK to downregulate human MK expression in human gastric cancer cell line BGC823 and SGC7901 so as to determine the advantages of this anticancer therapeutic. The cell proliferation was evaluated by a WST-8 (4-[3-(2-methoxy-4-nitrophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1, 3-benzene disulfonate sodium salt) assay and colony formation assay. Apoptosis was determined by flow cytometer analysis and colorimetric assay. Our results showed that the BGC823 and SGC7901 cell growth were significantly inhibited by knockdown of MK gene. The loss of mitochondrial membrane potential, release of cytochrome c from the mitochondria into cytosol and increased activity of caspase-3, 8 and 9 occurred concomitantly with inhibition of MK gene. These results indicated that siRNA targeting MK gene can inhibit gastric cancer cells growth and induce apoptosis via mitochondrial depolarization and caspase-3 activation. MK siRNA may be a promising novel and potential therapeutic strategy for the treatment of gastric cancers.

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978: Introduction of Midkine Gene Into Human Bladder Cancer Cells Enhances their Malignant Phenotype but Inceases in Sensitivity to Antiangiogenic Agent, TNP-470

Cited by 20 publications

References 0 publications

Combined proteome and transcriptome analyses for the discovery of urinary biomarkers for urothelial carcinoma

Combined proteome and transcriptome analyses for the discovery of urinary biomarkers for urothelial carcinoma

Nanoparticles for urothelium penetration and delivery of the histone deacetylase inhibitor belinostat for treatment of bladder cancer

siRNA targeting midkine inhibits gastric cancer cells growth and induces apoptosis involved caspase-3,8,9 activation and mitochondrial depolarization

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